Biological evaluation of novel curcumin-pyrazole-mannich derivative active against drug-resistant Mycobacterium tuberculosis

被引：10

作者：

Singh, Alok Kumar ^{[1
]}

Yadav, Pragya ^{[2
]}

Karaulia, Pratiksha ^{[1
]}

Singh, Vinay Kumar ^{[2
]}

Gupta, Pushpa ^{[4
]}

Puttrevu, Santosh Kumar ^{[3
]}

Chauhan, Sanjay ^{[3
]}

Bhatta, Rabi S. ^{[3
,5
]}

Tadigoppula, Narender ^{[2
,5
]}

Gupta, Umesh D.

Chopra, Sidharth ^{[1
,5
]}

Dasgupta, Arunava ^{[1
,5
]}

机构：

[1] CSIR, Cent Drug Res Inst, Div Microbiol, Sitapur Rd,Sect 10, Lucknow 226031, Uttar Pradesh, India

[2] CSIR, Cent Drug Res Inst, Med & Proc Chem, Sitapur Rd,Sect 10, Lucknow 226031, Uttar Pradesh, India

[3] CSIR, Cent Drug Res Inst, Div Pharmacokinet & Metab, Sitapur Rd,Sect 10, Lucknow 226031, Uttar Pradesh, India

[4] Natl JALMA Inst Leprosy & Other Mycobacterial Dis, Dr M Miyazaki Marg,POB 101, Agra 282001, Uttar Pradesh, India

[5] Acad Sci & Innovat Res, New Delhi 110025, India

来源：

FUTURE MICROBIOLOGY | 2017年 / 12卷 / 15期

关键词：

antibiotics; curcumin; drug resistance; Mycobacterium tuberculosis; pyrazole; DEGRADATION-PRODUCTS; ANALOGS; STABILITY; GROWTH; AGENTS;

D O I：

10.2217/fmb-2017-0054

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Aim: Our objective was to identify a more potent curcumin derivative with specific activity against Mycobacterium tuberculosis. Materials & methods: A total of 21 curcumin derivatives were synthesized and detailed bio-evaluation was carried out including determination of static/cidality, synergy with front-line antituberculosis drugs and determination of efficacy in the murine model of M. tuberculosis infection. Results: We identified CPMD-6d dihydrochloride exhibiting concentration-dependent bactericidal activity against M. tuberculosis (MIC 2 mu g/ml), even against drug-resistant strains. In addition, it synergizes with front-line antituberculosis drugs as well as significantly reduces bacterial load in mice lungs and spleen at 25 mg/kg as compared with ethambutol at 100 mg/kg. Conclusion: Taken together, CPMD-6d dihydrochloride exhibits all properties to be positioned as a novel molecule of interest for treatment of tuberculosis.

引用

页码：1349 / 1362

页数：14

共 22 条

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