Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as <i>β</i>-lactamase inhibitors

Citation: Kai Zhang, Huai-Wei Ding, Hao Ju, Qi Huang, Li-Juan Zhang, Hong-Rui Song, De-Cai Fu. Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors[J]. Chinese Chemical Letters, 2015, 26(6): 801-803. doi: 10.1016/j.cclet.2015.04.025 shu

Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

Kai Zhang ^a, ,
Huai-Wei Ding ^a, ,
Hao Ju ^a, ,
Qi Huang ^a, ,
Li-Juan Zhang ^a, ,
Hong-Rui Song ^{a,
,} ,
De-Cai Fu ^{b,
,}

通讯作者: Hong-Rui Song,
De-Cai Fu,

摘要: A series of sulfenimine cephalosporin sulfoxide derivatives (7a-v) were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C β-lactamase cephalosporinase compared with the tazobactam. The most promising compounds 7c and 7n (IC₅₀ = 7.6 and 8.6 μmol/L, respectively) were further investigated in combination with cefradine against a variety of clinical isolated β-lactamase-producing bacterial strains.

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English

Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

Kai Zhang ^a, ,
Huai-Wei Ding ^a, ,
Hao Ju ^a, ,
Qi Huang ^a, ,
Li-Juan Zhang ^a, ,
Hong-Rui Song ^{a,
,} ,
De-Cai Fu ^{b,
,}

1.
a Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;
2.
b College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China

Corresponding author: Hong-Rui Song, De-Cai Fu,

Received Date: 10 December 2014
Available Online: 18 April 2015

Abstract: A series of sulfenimine cephalosporin sulfoxide derivatives (7a-v) were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C β-lactamase cephalosporinase compared with the tazobactam. The most promising compounds 7c and 7n (IC₅₀ = 7.6 and 8.6 μmol/L, respectively) were further investigated in combination with cefradine against a variety of clinical isolated β-lactamase-producing bacterial strains.

Key words:

1. [1] A. Copar, T. Prevec, B. Anžič, et al., Design, synthesis and bioactivity evaluation of tribactam β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 12 (2002) 971-975.[1] A. Copar, T. Prevec, B. Anžič, et al., Design, synthesis and bioactivity evaluation of tribactam β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 12 (2002) 971-975.
2. [2] X. Yang, Y.J. Zhou, P. He, et al., Activation free energy of Zn(II), Co(II) binding to metallo-β-lactamase ImiS, Chin. Chem. Lett. 25 (2014) 1323-1326.[2] X. Yang, Y.J. Zhou, P. He, et al., Activation free energy of Zn(II), Co(II) binding to metallo-β-lactamase ImiS, Chin. Chem. Lett. 25 (2014) 1323-1326.
3. [3] S.M. Drawz, R.A. Bonomo, Three decades of β-lactamase inhibitors, Clin. Microbiol. Rev. 23 (2010) 160-201.[3] S.M. Drawz, R.A. Bonomo, Three decades of β-lactamase inhibitors, Clin. Microbiol. Rev. 23 (2010) 160-201.
4. [4] J.D. Buynak, L. Vogeti, V.R. Doppalapudi, G.M. Solomon, H.S. Chen, Cephalosporinderived inhibitors of β-lactamase. Part 4: The C3 substituent, Bioorg. Med. Chem. Lett. 12 (2002) 1663-1666.[4] J.D. Buynak, L. Vogeti, V.R. Doppalapudi, G.M. Solomon, H.S. Chen, Cephalosporinderived inhibitors of β-lactamase. Part 4: The C3 substituent, Bioorg. Med. Chem. Lett. 12 (2002) 1663-1666.
5. [5] T. Muratani, E. Yokota, T. Nakane, E. Inoue, S. Mitsuhashi, In-vitro evaluation of the four β-lactamase inhibitors: BRL42715, clavulanic acid, sulbactam, and tazobactam, J. Antimicrob. Chemother. 32 (1993) 421-429.[5] T. Muratani, E. Yokota, T. Nakane, E. Inoue, S. Mitsuhashi, In-vitro evaluation of the four β-lactamase inhibitors: BRL42715, clavulanic acid, sulbactam, and tazobactam, J. Antimicrob. Chemother. 32 (1993) 421-429.
6. [6] E.B. Grant, D. Guiadeen, E.Z. Baum, et al., The synthesis and SAR of rhodanines as novel class C β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 10 (2000) 2179-2182.[6] E.B. Grant, D. Guiadeen, E.Z. Baum, et al., The synthesis and SAR of rhodanines as novel class C β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 10 (2000) 2179-2182.
7. [7] J.D. Buynak, V.R. Doppalapudi, G. Adam, The synthesis and evaluation of 3-substituted-7-(alkylidene)cephalosporin sulfones as β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 10 (2000) 853-857.[7] J.D. Buynak, V.R. Doppalapudi, G. Adam, The synthesis and evaluation of 3-substituted-7-(alkylidene)cephalosporin sulfones as β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 10 (2000) 853-857.
8. [8] K. Coleman, D.R.J. Griffin, J.W. Page, P.A. Upshon, In vitro evaluation of BRL42715, a novel β-lactamase inhibitor, Antimicrob. Agents Chemother. 33 (1989) 1580-1587.[8] K. Coleman, D.R.J. Griffin, J.W. Page, P.A. Upshon, In vitro evaluation of BRL42715, a novel β-lactamase inhibitor, Antimicrob. Agents Chemother. 33 (1989) 1580-1587.
9. [9] J.D. Buynak, A.S. Rao, V.R. Doppalapudi, et al., The synthesis and evaluation of 6-alkylidene-2' β-substituted penam sulfones as β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 9 (1999) 1997-2002.[9] J.D. Buynak, A.S. Rao, V.R. Doppalapudi, et al., The synthesis and evaluation of 6-alkylidene-2' β-substituted penam sulfones as β-lactamase inhibitors, Bioorg. Med. Chem. Lett. 9 (1999) 1997-2002.
10. [10] E.M. Gordon, H.W. Chang, C.M. Cimarusti, B. Toeplitz, J.Z. Gougoutas, Sulfenyl transfer rearrangement of sulfenimines (thiooximes). A novel synthesis of 7α-methoxycephalosporins and 6a-methoxypenicillins, J. Am. Chem. Soc. 102 (1980) 1690-1702.[10] E.M. Gordon, H.W. Chang, C.M. Cimarusti, B. Toeplitz, J.Z. Gougoutas, Sulfenyl transfer rearrangement of sulfenimines (thiooximes). A novel synthesis of 7α-methoxycephalosporins and 6a-methoxypenicillins, J. Am. Chem. Soc. 102 (1980) 1690-1702.
11. [11] L.S. Changov, E.D. Naydenova, G.I. Ivanova, et al., Synthesis and β-lactamase inhibitory activity of new 6β-cysteinesulfonamidopenicillanic acids, Bioorg. Med. Chem. 7 (1999) 2899-2904.[11] L.S. Changov, E.D. Naydenova, G.I. Ivanova, et al., Synthesis and β-lactamase inhibitory activity of new 6β-cysteinesulfonamidopenicillanic acids, Bioorg. Med. Chem. 7 (1999) 2899-2904.
12. [12] Y.J. Yang, R.T. Testa, N. Bhachech, et al., Biochemical characterization of novel tetrahydrofuranyl 1β-methylcarba-penems: stability to hydrolysis by renal dehydropeptidases and bacterial β-lactamases, binding to penicillin binding proteins, and permeability properties, Antimicrob. Agents Chemother. 43 (1999) 2904-2909.[12] Y.J. Yang, R.T. Testa, N. Bhachech, et al., Biochemical characterization of novel tetrahydrofuranyl 1β-methylcarba-penems: stability to hydrolysis by renal dehydropeptidases and bacterial β-lactamases, binding to penicillin binding proteins, and permeability properties, Antimicrob. Agents Chemother. 43 (1999) 2904-2909.

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

通讯作者: Hong-Rui Song,
De-Cai Fu,

English

Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

Corresponding author: Hong-Rui Song, De-Cai Fu,

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

通讯作者: Hong-Rui Song, De-Cai Fu,

English

Design, synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

Corresponding author: Hong-Rui Song, De-Cai Fu,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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