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2014 Volume 25 Issue 7
2014, 25(7): 937-977
doi: 10.1016/j.cclet.2014.05.046
Abstract:
Bioactive compounds could form aggregates that influence the bio-interactive processes. In this letter, based on π-π stacking models, quantitative aggregation-activity relationship (QAAR) studies were carried out on a series of sulfonylurea herbicides with good solubility. Four QAAR/QSAR models were constructed, which indicated that the bioactivity may strongly depend on both the characters of the dimeric aggregates and the monomer. The QAAR approach based on dimer-aggregates was also applicable for the highly water-soluble sulfonylurea herbicides that can form π-π stacking interactions. It was expected that the QAAR studies based on molecular aggregation state would be applied to other pesticide systems.
Bioactive compounds could form aggregates that influence the bio-interactive processes. In this letter, based on π-π stacking models, quantitative aggregation-activity relationship (QAAR) studies were carried out on a series of sulfonylurea herbicides with good solubility. Four QAAR/QSAR models were constructed, which indicated that the bioactivity may strongly depend on both the characters of the dimeric aggregates and the monomer. The QAAR approach based on dimer-aggregates was also applicable for the highly water-soluble sulfonylurea herbicides that can form π-π stacking interactions. It was expected that the QAAR studies based on molecular aggregation state would be applied to other pesticide systems.
2014, 25(7): 978-982
doi: 10.1016/j.cclet.2014.03.043
Abstract:
A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase I and II was evaluated by the relaxation assay. In vitro antitumor activity results revealed that compound 12 showed good antitumor activity with a broad spectrum. Its binding modes with topoisomerase I and II were clarified by molecular docking.
A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase I and II was evaluated by the relaxation assay. In vitro antitumor activity results revealed that compound 12 showed good antitumor activity with a broad spectrum. Its binding modes with topoisomerase I and II were clarified by molecular docking.
2014, 25(7): 983-988
doi: 10.1016/j.cclet.2014.05.045
Abstract:
Laccase is a promising oxidase with environmental applications, such as lignin degradation and chlorophenol detoxification. Laccase immobilization can significantly improve physiochemical stability and reusability compared to the free enzymes. In this work, anion effect was investigated in entrapment of Cu-alginate matrix with five types of anions, including perchlorate (ClO4-), nitrate (NO3-), sulfate (SO42- ), chloride (Cl-), and acetate (CH3CO2-). Accordingly, chloride inhibition and acetate activation were detected in the o-tolidine kinetic experiments, while effects of the other three anions were much smaller. Such counteranion effects were also observed in the laccase-catalyzed biodegradation of 2,4-dichlorophenol. The results indicated that counteranions in the enzyme immobilization process are crucial for catalytic capacity, probably due to the competition with the carboxylate groups in alginate. Our results also imply that these anions might coordinate the copper cations in laccase.
Laccase is a promising oxidase with environmental applications, such as lignin degradation and chlorophenol detoxification. Laccase immobilization can significantly improve physiochemical stability and reusability compared to the free enzymes. In this work, anion effect was investigated in entrapment of Cu-alginate matrix with five types of anions, including perchlorate (ClO4-), nitrate (NO3-), sulfate (SO42- ), chloride (Cl-), and acetate (CH3CO2-). Accordingly, chloride inhibition and acetate activation were detected in the o-tolidine kinetic experiments, while effects of the other three anions were much smaller. Such counteranion effects were also observed in the laccase-catalyzed biodegradation of 2,4-dichlorophenol. The results indicated that counteranions in the enzyme immobilization process are crucial for catalytic capacity, probably due to the competition with the carboxylate groups in alginate. Our results also imply that these anions might coordinate the copper cations in laccase.
2014, 25(7): 989-994
doi: 10.1016/j.cclet.2014.06.010
Abstract:
A series of novel, cycloalkyl-modified pazopanib analogs 2 and 3 were designed and synthesized. Their kinase modulatory effects on FGFR-1, VEGFR-2, PDGFR-β, and c-KIT were evaluated by the caliper mobility shift assay. Introduction of cycloalkyl into the pyrimidine linker of pazopanib almost abolished the four kinases inhibitory potency of compounds 2 and 3, but surprisingly, resulted in good activation effects on FGFR-1. Compounds 3d and 3g showed double-digit, nanomolar, selective activation effects on FGFR-1, and could be classified as first-generation small molecular activators of FGFR-1 kinase.
A series of novel, cycloalkyl-modified pazopanib analogs 2 and 3 were designed and synthesized. Their kinase modulatory effects on FGFR-1, VEGFR-2, PDGFR-β, and c-KIT were evaluated by the caliper mobility shift assay. Introduction of cycloalkyl into the pyrimidine linker of pazopanib almost abolished the four kinases inhibitory potency of compounds 2 and 3, but surprisingly, resulted in good activation effects on FGFR-1. Compounds 3d and 3g showed double-digit, nanomolar, selective activation effects on FGFR-1, and could be classified as first-generation small molecular activators of FGFR-1 kinase.
2014, 25(7): 995-1000
doi: 10.1016/j.cclet.2014.06.002
Abstract:
A new method has been proposed to realize the visual detection of D-amino acids (DAAs) via the antiaggregation of 4-mercaptobenzoic acid modified gold nanoparticles (AuNPs) in the presence of D-amino acid oxidase (DAAO). The negatively charged AuNPs were prepared using sodium citrate as a reducer and stabilizer. The presence of 4-mercaptobenzoic acid (4-MBA) and Cu2+ induces the aggregation of AuNPs, resulting in a color change from ruby red to royal purple. However, DAAO could oxidize DAAs to generate H2O2. In the presence of H2O2, the mercapto (-SH) group in 4-mercaptobenzoic acid can be oxidized to form a disulfide (-S-S-) bond. Based on these facts, the pre-incubation of DAAs and 4-mercaptobenzoic acid with DAAO would significantly reduce the concentration of free 4-mercaptobenzoic acidmolecules, thus the aggregation of AuNPs was interrupted since due to the lack of inducer. As the concentration of DAAs increases, the color of the AuNPs solution would progress from royal purple to ruby red. Consequently, DAAs could be monitored by the colorimetric response of AuNPs using a UV-vis spectrophotometer or even naked eyes. This DAAO mediated visual detectionmethod could determine Dalanine (D-Ala) as a representative DAA with concentrations ranging from 1.5×10-7 mol L-1 to 3.0×10-5 mol L-1, and the detection limit was as low as 7.5×10-8 mol L-1. The proposed method is convenient, low-cost and free of complex equipment, making it feasible to analyze the concentration of D-Ala in real samples of β-amyloid peptide (Aβ1-42).
A new method has been proposed to realize the visual detection of D-amino acids (DAAs) via the antiaggregation of 4-mercaptobenzoic acid modified gold nanoparticles (AuNPs) in the presence of D-amino acid oxidase (DAAO). The negatively charged AuNPs were prepared using sodium citrate as a reducer and stabilizer. The presence of 4-mercaptobenzoic acid (4-MBA) and Cu2+ induces the aggregation of AuNPs, resulting in a color change from ruby red to royal purple. However, DAAO could oxidize DAAs to generate H2O2. In the presence of H2O2, the mercapto (-SH) group in 4-mercaptobenzoic acid can be oxidized to form a disulfide (-S-S-) bond. Based on these facts, the pre-incubation of DAAs and 4-mercaptobenzoic acid with DAAO would significantly reduce the concentration of free 4-mercaptobenzoic acidmolecules, thus the aggregation of AuNPs was interrupted since due to the lack of inducer. As the concentration of DAAs increases, the color of the AuNPs solution would progress from royal purple to ruby red. Consequently, DAAs could be monitored by the colorimetric response of AuNPs using a UV-vis spectrophotometer or even naked eyes. This DAAO mediated visual detectionmethod could determine Dalanine (D-Ala) as a representative DAA with concentrations ranging from 1.5×10-7 mol L-1 to 3.0×10-5 mol L-1, and the detection limit was as low as 7.5×10-8 mol L-1. The proposed method is convenient, low-cost and free of complex equipment, making it feasible to analyze the concentration of D-Ala in real samples of β-amyloid peptide (Aβ1-42).
2014, 25(7): 1001-1005
doi: 10.1016/j.cclet.2014.05.020
Abstract:
PAHPN, a naphthalimide-based mitotracker with reasonable two-photon excitation emission activity and polarity-sensitive fluorescence properties has been efficiently synthesized and studied in twophoton, co-localization, and FLIM imaging.
PAHPN, a naphthalimide-based mitotracker with reasonable two-photon excitation emission activity and polarity-sensitive fluorescence properties has been efficiently synthesized and studied in twophoton, co-localization, and FLIM imaging.
2014, 25(7): 1006-1010
doi: 10.1016/j.cclet.2014.05.043
Abstract:
A series of novel 2-trifluoromethylthieno[2,3-d]pyrimidine derivatives were synthesized by a facile three-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The structures of the final compounds were confirmed by IR, NMR, EI-MS, elemental analysis, and X-ray diffraction. Preliminary bioassay results showed that some of the analogs exhibit excellent antitumor activity against MCF-7 and HepG2, especially compounds 3a, 3b, 3e and 3h exhibited higher activity than the positive control gefitinib.
A series of novel 2-trifluoromethylthieno[2,3-d]pyrimidine derivatives were synthesized by a facile three-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The structures of the final compounds were confirmed by IR, NMR, EI-MS, elemental analysis, and X-ray diffraction. Preliminary bioassay results showed that some of the analogs exhibit excellent antitumor activity against MCF-7 and HepG2, especially compounds 3a, 3b, 3e and 3h exhibited higher activity than the positive control gefitinib.
2014, 25(7): 1011-1013
doi: 10.1016/j.cclet.2014.04.026
Abstract:
A series of novel 2-amino-4H-pyran derivatives have been synthesized via a three-component reaction of a, β-unsaturated ketone derivatives, malononitrile, aldehydes in excellent yields, using DBU as a catalyst and ethanol as a cheap, safe, and environmentally benign solvent under mild conditions. Their antitumor activity was evaluated in three human tumor cell lines, including human colon cancer (HCT116), human cervical cancer (Hela), and non-small cell lung cancer (H1975).
A series of novel 2-amino-4H-pyran derivatives have been synthesized via a three-component reaction of a, β-unsaturated ketone derivatives, malononitrile, aldehydes in excellent yields, using DBU as a catalyst and ethanol as a cheap, safe, and environmentally benign solvent under mild conditions. Their antitumor activity was evaluated in three human tumor cell lines, including human colon cancer (HCT116), human cervical cancer (Hela), and non-small cell lung cancer (H1975).
2014, 25(7): 1014-1016
doi: 10.1016/j.cclet.2014.06.011
Abstract:
A series of new pyrazole oximes bearing substituted thiazole ring were designed and prepared. The structures of the title compounds were identified by spectral analyses. The results of primary bioassay indicated that some targeted compounds exhibited promising insecticidal activity besides acaricidal activity, particularly; compounds 8c and 8d were more potent against Tetranychus cinnabarinus and Plutella xylostella than other analogues.
A series of new pyrazole oximes bearing substituted thiazole ring were designed and prepared. The structures of the title compounds were identified by spectral analyses. The results of primary bioassay indicated that some targeted compounds exhibited promising insecticidal activity besides acaricidal activity, particularly; compounds 8c and 8d were more potent against Tetranychus cinnabarinus and Plutella xylostella than other analogues.
2014, 25(7): 1017-1020
doi: 10.1016/j.cclet.2014.03.026
Abstract:
A series of novel neonicotinoid analogues were designed and synthesized by introducing a hydrazide group into clothianidin. Their structures were confirmed by IR, 1H NMR, and HRMS (ESI). Preliminary bioassay showed that some compounds, 5b and 5g, exhibited good activity against soybean aphids (Aphis glycines) at 100 mg L 1. In addition, molecular docking with receptor was carried out to explain their different activity from clothianidin.
A series of novel neonicotinoid analogues were designed and synthesized by introducing a hydrazide group into clothianidin. Their structures were confirmed by IR, 1H NMR, and HRMS (ESI). Preliminary bioassay showed that some compounds, 5b and 5g, exhibited good activity against soybean aphids (Aphis glycines) at 100 mg L 1. In addition, molecular docking with receptor was carried out to explain their different activity from clothianidin.
2014, 25(7): 1021-1024
doi: 10.1016/j.cclet.2014.03.028
Abstract:
Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.
Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.
2014, 25(7): 1025-1028
doi: 10.1016/j.cclet.2014.05.048
Abstract:
A series of new 3-benzoheterocyclic substituted pyridopyrimidines were designed and synthesized. Structures of the compounds were determined by IR, 1H NMR, and elemental analyses. The antiproliferation activity of 13 novel compounds was evaluated in A549, HL-60, BGC-823 and SMMC-7721 cell lines. Compounds 3, 5, 7, 8, 9, 10 showed potent inhibitory activity against the four tested cancer cell lines. These six compounds were examined for Top I inhibition at 100 mmol/L by measuring the relaxation of supercoiled DNA in plasmid pBR322. Most of the tested compounds inhibited the enzyme at this concentration. The most potent compound 9 was as potent as camptothecin.
A series of new 3-benzoheterocyclic substituted pyridopyrimidines were designed and synthesized. Structures of the compounds were determined by IR, 1H NMR, and elemental analyses. The antiproliferation activity of 13 novel compounds was evaluated in A549, HL-60, BGC-823 and SMMC-7721 cell lines. Compounds 3, 5, 7, 8, 9, 10 showed potent inhibitory activity against the four tested cancer cell lines. These six compounds were examined for Top I inhibition at 100 mmol/L by measuring the relaxation of supercoiled DNA in plasmid pBR322. Most of the tested compounds inhibited the enzyme at this concentration. The most potent compound 9 was as potent as camptothecin.
2014, 25(7): 1029-1032
doi: 10.1016/j.cclet.2014.05.009
Abstract:
Nanopore technique plays an important role in single molecule detection, which illuminates the properties of an individual molecule by analyzing the blockage durations and currents. However, the traditional exponential function is lack of efficiency to describe the distributions of blockage durations in nanopore experiments. Herein, we introduced an exponentially modified Gaussian (EMG) function to fit the duration histograms of both simulated events and experimental events. In comparison with the traditional exponential function, our results demonstrated that the EMG provides a better fit while covers the entire range of the distributions. In particular, the fitted parameters of EMG could be directly used to discriminate the sequence length of the oligonucleotides at single molecule level.
Nanopore technique plays an important role in single molecule detection, which illuminates the properties of an individual molecule by analyzing the blockage durations and currents. However, the traditional exponential function is lack of efficiency to describe the distributions of blockage durations in nanopore experiments. Herein, we introduced an exponentially modified Gaussian (EMG) function to fit the duration histograms of both simulated events and experimental events. In comparison with the traditional exponential function, our results demonstrated that the EMG provides a better fit while covers the entire range of the distributions. In particular, the fitted parameters of EMG could be directly used to discriminate the sequence length of the oligonucleotides at single molecule level.
2014, 25(7): 1033-1038
doi: 10.1016/j.cclet.2014.04.003
Abstract:
A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a-i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylaminopyridine (DMAP) as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14ademethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.
A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a-i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylaminopyridine (DMAP) as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14ademethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.
2014, 25(7): 1039-1043
doi: 10.1016/j.cclet.2014.04.029
Abstract:
The formation of advanced glycation end-products (AGEs) and aldose reductase (AR) activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose (fructose) system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions. Compared with other screened herbs used in our study, Flos Sophorae Immaturus and Radix Scutellariae seemed to bemore effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vivo, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.
The formation of advanced glycation end-products (AGEs) and aldose reductase (AR) activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose (fructose) system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions. Compared with other screened herbs used in our study, Flos Sophorae Immaturus and Radix Scutellariae seemed to bemore effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vivo, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.
2014, 25(7): 1044-1046
doi: 10.1016/j.cclet.2014.05.042
Abstract:
The novel justicidin G analogue 13 and its phosphate ester 15 were synthesized as potential anticancer agents in several steps starting from commercially available methyl gallate and veratraldehyde. The cytotoxicity of the intermediates was tested against HCT-8, BEL-7402, KETR3, HELA, BGC-823, KB and MCF-7 cell lines by the MTT test, and compound 15 exhibited significant cytotoxicity in HELA and KB cell lines.
The novel justicidin G analogue 13 and its phosphate ester 15 were synthesized as potential anticancer agents in several steps starting from commercially available methyl gallate and veratraldehyde. The cytotoxicity of the intermediates was tested against HCT-8, BEL-7402, KETR3, HELA, BGC-823, KB and MCF-7 cell lines by the MTT test, and compound 15 exhibited significant cytotoxicity in HELA and KB cell lines.
2014, 25(7): 1047-1051
doi: 10.1016/j.cclet.2014.05.002
Abstract:
This work develops a fluorescence approach for sensitive detection of DNA methyltransferase activity based on endonuclease and rolling circle amplification (RCA) technique. In the presence of DNA adenine methylation (Dam) MTase, the methylation-responsive sequence of hairpin probe is methylated and cleaved by the methylation-sensitive restriction endonuclease Dpn I. The products cleaved by restriction endonuclease Dpn I then function as a signal primer to initiate RCA reaction by hybridizing with the circular DNA template. Each RCA product containing thousands of repeated sequences might hybridize with a large number of molecular beacons (detection probes), resulting in an enhanced fluorescence signal. In the absence of Dam MTase, neithermethylation/cleavage nor RCA reaction can be initiated and no fluorescence signal is observed. The proposed method exhibits a dynamic range from 0.5 U/mL to 30 U/mL and a detection limit of 0.18 U/mL. This method can be used for the screening of antimicrobial drugs and has a great potential to be further applied in early clinical diagnosis.
This work develops a fluorescence approach for sensitive detection of DNA methyltransferase activity based on endonuclease and rolling circle amplification (RCA) technique. In the presence of DNA adenine methylation (Dam) MTase, the methylation-responsive sequence of hairpin probe is methylated and cleaved by the methylation-sensitive restriction endonuclease Dpn I. The products cleaved by restriction endonuclease Dpn I then function as a signal primer to initiate RCA reaction by hybridizing with the circular DNA template. Each RCA product containing thousands of repeated sequences might hybridize with a large number of molecular beacons (detection probes), resulting in an enhanced fluorescence signal. In the absence of Dam MTase, neithermethylation/cleavage nor RCA reaction can be initiated and no fluorescence signal is observed. The proposed method exhibits a dynamic range from 0.5 U/mL to 30 U/mL and a detection limit of 0.18 U/mL. This method can be used for the screening of antimicrobial drugs and has a great potential to be further applied in early clinical diagnosis.
Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine
2014, 25(7): 1052-1056
doi: 10.1016/j.cclet.2014.05.030
Abstract:
A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV-1 activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1IIIB into target cell, which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosaminewere important moities to prepare gossypol derivatives as HIV-1 entry inhibitors besides certain amino acids.
A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV-1 activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1IIIB into target cell, which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosaminewere important moities to prepare gossypol derivatives as HIV-1 entry inhibitors besides certain amino acids.
2014, 25(7): 1057-1059
doi: 10.1016/j.cclet.2014.05.029
Abstract:
A series of novel, azasugar-modified 2-monosubstituted, 2,6-and 2,7-bissubstituted anthraquinone derivatives have been synthesized by the nucleophilic substitution of N-alkylamino azasugar with mono-, bis(2-chloroacetamido)anthraquinones. Their cytotoxic activities against HeLa and MCF-7 cells were preliminarily evaluated and compound 9a with mono-azasugar pendant at 2-position showed similar activity to the control drug (Cisplatin).
A series of novel, azasugar-modified 2-monosubstituted, 2,6-and 2,7-bissubstituted anthraquinone derivatives have been synthesized by the nucleophilic substitution of N-alkylamino azasugar with mono-, bis(2-chloroacetamido)anthraquinones. Their cytotoxic activities against HeLa and MCF-7 cells were preliminarily evaluated and compound 9a with mono-azasugar pendant at 2-position showed similar activity to the control drug (Cisplatin).
2014, 25(7): 1060-1064
doi: 10.1016/j.cclet.2014.05.010
Abstract:
In this work, a fluorescein-derived fluorescent probe for H2S based on the thiolysis of dinitrophenyl ether is reported. This probe exhibits turn-on fluorescence imaging of H2S in living cells and bulk solutions with excellent selectivity. The reaction mechanism was explained by means of absorption, fluorescence and HPLC-MS.
In this work, a fluorescein-derived fluorescent probe for H2S based on the thiolysis of dinitrophenyl ether is reported. This probe exhibits turn-on fluorescence imaging of H2S in living cells and bulk solutions with excellent selectivity. The reaction mechanism was explained by means of absorption, fluorescence and HPLC-MS.
2014, 25(7): 1065-1068
doi: 10.1016/j.cclet.2014.04.033
Abstract:
A new fluorescent "on-off" chemosensor for Hg2+ initiated by a derivative of rhodamine B was designed and synthesized. Compound 1 exhibited high sensitivity and selectivity for Hg2+ over other commonly coexistent metal ions in aqueous media. Upon the addition of Hg2+, the spirocyclic ring of probe is opened and a significant enhancement of visible color and fluorescence in the range of 500-600 nm is observed. The colorimetric and fluorescent response to Hg2+ can be conveniently detected by the naked eye, which provides a facile method for visual detection of Hg2+. From the molecular structure and spectral results of 1, an irreversible, hydrolysis, desulfurization reaction mechanism is proposed.
A new fluorescent "on-off" chemosensor for Hg2+ initiated by a derivative of rhodamine B was designed and synthesized. Compound 1 exhibited high sensitivity and selectivity for Hg2+ over other commonly coexistent metal ions in aqueous media. Upon the addition of Hg2+, the spirocyclic ring of probe is opened and a significant enhancement of visible color and fluorescence in the range of 500-600 nm is observed. The colorimetric and fluorescent response to Hg2+ can be conveniently detected by the naked eye, which provides a facile method for visual detection of Hg2+. From the molecular structure and spectral results of 1, an irreversible, hydrolysis, desulfurization reaction mechanism is proposed.
2014, 25(7): 1069-1072
doi: 10.1016/j.cclet.2014.03.046
Abstract:
With the increase of herbicide-resistant weeds, novel, more selective and even more potent herbicides to control weeds are needed. In this paper, a series of N-Fluorinated phenyl-N'-pyrimidyl urea derivatives were synthesized and screened for their herbicidal activities against Amaranthus retroflexus (AR) and Setaria viridis (SV). Compound 25 (N-(3-trifluoromethylphenyl)-N'-(2-amino-4-chloro-6-methylpyrimidyl) urea) exhibited marked herbicidal activity against SV (IC50=11.67 mg/L) and is more potent than bensulfuron (IC50=27.45 mg/L), a commercially available herbicide. A statistically significant CoMFA model with high prediction abilities (q2=0.869, r2=0.989) was obtained.
With the increase of herbicide-resistant weeds, novel, more selective and even more potent herbicides to control weeds are needed. In this paper, a series of N-Fluorinated phenyl-N'-pyrimidyl urea derivatives were synthesized and screened for their herbicidal activities against Amaranthus retroflexus (AR) and Setaria viridis (SV). Compound 25 (N-(3-trifluoromethylphenyl)-N'-(2-amino-4-chloro-6-methylpyrimidyl) urea) exhibited marked herbicidal activity against SV (IC50=11.67 mg/L) and is more potent than bensulfuron (IC50=27.45 mg/L), a commercially available herbicide. A statistically significant CoMFA model with high prediction abilities (q2=0.869, r2=0.989) was obtained.
2014, 25(7): 1073-1076
doi: 10.1016/j.cclet.2014.04.002
Abstract:
A new series of 2-thiophenoxyquinolines based trifluoromethyl substituted N-aryl quinolone derivatives 8a-f and 9a-f have been synthesized via a one-pot multicomponent reaction. In vitro antimicrobial activity of the synthesized compounds was investigated against a representative panel of pathogenic strains. Compounds 8c, 9c and 9e exhibited comparable antimicrobial activity to first line drugs.
A new series of 2-thiophenoxyquinolines based trifluoromethyl substituted N-aryl quinolone derivatives 8a-f and 9a-f have been synthesized via a one-pot multicomponent reaction. In vitro antimicrobial activity of the synthesized compounds was investigated against a representative panel of pathogenic strains. Compounds 8c, 9c and 9e exhibited comparable antimicrobial activity to first line drugs.
2014, 25(7): 1077-1081
doi: 10.1016/j.cclet.2014.05.011
Abstract:
A series of novel and convenient fluorescent probes with Schiff base functionality were presented for direct detection of OCl- via the irreversible OCl--promoted oxidation and hydrolyzation reaction in formation of the ring-opened product, fluorescein. Prominent high sensitivity, selectivity and antiinterference OCl--induced fluorescence and color change over a wide range of tested metal ions performance were observed for each probe under physiological conditions, thus making the probes well suitable for sensing of OCl-in living cells.
A series of novel and convenient fluorescent probes with Schiff base functionality were presented for direct detection of OCl- via the irreversible OCl--promoted oxidation and hydrolyzation reaction in formation of the ring-opened product, fluorescein. Prominent high sensitivity, selectivity and antiinterference OCl--induced fluorescence and color change over a wide range of tested metal ions performance were observed for each probe under physiological conditions, thus making the probes well suitable for sensing of OCl-in living cells.
2014, 25(7): 1082-1086
doi: 10.1016/j.cclet.2014.05.001
Abstract:
A novel, fluorescent probe was synthesized from 2,4-dihydroxybenzaldehyde and 8-hydroxyquinoline for sensing Cu2+ by the naked eye. The structure was confirmed by IR, MS, 1H NMR, 13C NMR and the spectral properties of the probe were investigated. It exhibited strong fluorescence responses toward Cu2+ and high selectivity over other metal ions. The binding constant between the probe and Cu2+ was calculated using Benesi-Hildebrand equation.
A novel, fluorescent probe was synthesized from 2,4-dihydroxybenzaldehyde and 8-hydroxyquinoline for sensing Cu2+ by the naked eye. The structure was confirmed by IR, MS, 1H NMR, 13C NMR and the spectral properties of the probe were investigated. It exhibited strong fluorescence responses toward Cu2+ and high selectivity over other metal ions. The binding constant between the probe and Cu2+ was calculated using Benesi-Hildebrand equation.
2014, 25(7): 1087-1093
doi: 10.1016/j.cclet.2014.04.020
Abstract:
A series of novel naphthalimide derivatives modified by amino acids and their dichloroacetamide derivatives at the 3-position have been synthesized. Their cytotoxic activities were preliminarily evaluated against Hela, A549 and K562 cells, which showed that the length of the side chains of the amino acids influenced the cytotoxic activities. Moreover, compound 7d showed a very good cytotoxic activity against A549 cells with an IC50 value of 4.78 mmol L-1. Furthermore, the UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation experiment indicated that compounds 6a, 6d and 7a, 7d, as DNA intercalators, exhibited binding affinities with calf-thymus DNA (Ct-DNA).
A series of novel naphthalimide derivatives modified by amino acids and their dichloroacetamide derivatives at the 3-position have been synthesized. Their cytotoxic activities were preliminarily evaluated against Hela, A549 and K562 cells, which showed that the length of the side chains of the amino acids influenced the cytotoxic activities. Moreover, compound 7d showed a very good cytotoxic activity against A549 cells with an IC50 value of 4.78 mmol L-1. Furthermore, the UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation experiment indicated that compounds 6a, 6d and 7a, 7d, as DNA intercalators, exhibited binding affinities with calf-thymus DNA (Ct-DNA).
2014, 25(7): 1094-1098
doi: 10.1016/j.cclet.2014.05.021
Abstract:
Several derivatives have been synthesized from chrysin, diosmetin, apigenin, and luteolin, which were isolated from diverse natural plants. The a-glucosidase inhibitory activity of these compounds was evaluated. The glucosidase inhibitory activity of all derivatives (IC50 < 24.396 μmol/L) was higher compared with that of the reference drug, acarbose (IC50=563.601±40.492 mmol/L), and 1-deoxynojirimycin (IC50=226.912±12.573 μmol/L). O3',7-Hexyl diosmetin (IC50=2.406 0.101 mmol/L) was the most potent inhibitor identified. These compounds showed a higher inhibitory ability compared with their precursors except the luteolin derivatives. In general, the inhibitory activity of the synthetic derivatives was enhanced with long alkyl chains at positions 3', 4' and 7 of the flavonoid.
Several derivatives have been synthesized from chrysin, diosmetin, apigenin, and luteolin, which were isolated from diverse natural plants. The a-glucosidase inhibitory activity of these compounds was evaluated. The glucosidase inhibitory activity of all derivatives (IC50 < 24.396 μmol/L) was higher compared with that of the reference drug, acarbose (IC50=563.601±40.492 mmol/L), and 1-deoxynojirimycin (IC50=226.912±12.573 μmol/L). O3',7-Hexyl diosmetin (IC50=2.406 0.101 mmol/L) was the most potent inhibitor identified. These compounds showed a higher inhibitory ability compared with their precursors except the luteolin derivatives. In general, the inhibitory activity of the synthetic derivatives was enhanced with long alkyl chains at positions 3', 4' and 7 of the flavonoid.
2014, 25(7): 1099-1103
doi: 10.1016/j.cclet.2014.03.044
Abstract:
A convenient one-pot three-component method for the preparation of tetra-substituted thiophene derivatives has been developed. Reaction of acetyl acetone 1, phenyl isothiocynate 2 and 2-chloromethyl derivatives 3a-3c in the presence of potassium carbonate afforded the target compounds, namely ethyl 2-(4-acetyl-3-methyl-5-(phenylamino)thiophen-2-yl)-2-oxoacetate derivatives 4a-4e, ethyl 3-(4-acetyl-3-methyl-5-(phenylamino)thiophen-2-yl)-3-oxopropanoate derivatives 4f-4i, di((4-acetyl-3-methyl-5-phenylamino)thiophen-2-yl)ketone derivatives 4j-4n in reasonable overall yields. The synthesized compounds were screened for antimicrobial activity. The detailed synthesis, spectroscopic data and antimicrobial activities of synthesized compounds were reported.
A convenient one-pot three-component method for the preparation of tetra-substituted thiophene derivatives has been developed. Reaction of acetyl acetone 1, phenyl isothiocynate 2 and 2-chloromethyl derivatives 3a-3c in the presence of potassium carbonate afforded the target compounds, namely ethyl 2-(4-acetyl-3-methyl-5-(phenylamino)thiophen-2-yl)-2-oxoacetate derivatives 4a-4e, ethyl 3-(4-acetyl-3-methyl-5-(phenylamino)thiophen-2-yl)-3-oxopropanoate derivatives 4f-4i, di((4-acetyl-3-methyl-5-phenylamino)thiophen-2-yl)ketone derivatives 4j-4n in reasonable overall yields. The synthesized compounds were screened for antimicrobial activity. The detailed synthesis, spectroscopic data and antimicrobial activities of synthesized compounds were reported.
2014, 25(7): 1104-1106
doi: 10.1016/j.cclet.2014.02.006
Abstract:
Three new C-3 dehydrated bufadienolides were isolated from the venom of Bufo bufo gargarizans. Their structures were elucidated as 5β,12β-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide (1), 5β,12α-12,14-dihydroxy-11-oxobufa-2,20,22-trienolide (2), and 5β,12β-12,14-dihydroxy-11-oxobufa-2,20,22-trienolide (3) on the basis of extensive spectroscopic analysis, especially 1D NMR and 2D NMR data. In addition, all three compounds were tested for their cytotoxic activities against A549 and HepG2 cancer cell lines. Compounds 2 and 3 showed significant cytotoxicities with IC50 values less than 10 μmol/L on both cancer cells.
Three new C-3 dehydrated bufadienolides were isolated from the venom of Bufo bufo gargarizans. Their structures were elucidated as 5β,12β-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide (1), 5β,12α-12,14-dihydroxy-11-oxobufa-2,20,22-trienolide (2), and 5β,12β-12,14-dihydroxy-11-oxobufa-2,20,22-trienolide (3) on the basis of extensive spectroscopic analysis, especially 1D NMR and 2D NMR data. In addition, all three compounds were tested for their cytotoxic activities against A549 and HepG2 cancer cell lines. Compounds 2 and 3 showed significant cytotoxicities with IC50 values less than 10 μmol/L on both cancer cells.
