Pyrazole-coumarin and pyrazole-quinoline chalcones as potential antitubercular agents

被引：44

作者：

Kumar, Gautam ^{[1
]}

Siva Krishna, Vagolu ^{[2
]}

Sriram, Dharmarajan ^{[2
]}

Jachak, Sanjay M. ^{[1
]}

机构：

[1] Natl Inst Pharmaceut Educ & Res NIPER, Dept Nat Prod, Sect 67, Mohali 160062, Punjab, India

[2] Birla Inst Technol & Sci Pilani, Med Chem & Antimycobacterial Res Lab, Pharm Grp, Hyderabad, Andhra Pradesh, India

来源：

ARCHIV DER PHARMAZIE | 2020年 / 353卷 / 08期

关键词：

antimycobacterial activity; cytotoxic activity; pyrazole; synthesis; MYCOBACTERIUM-TUBERCULOSIS; MOLECULAR DOCKING; DPRE1; ENZYME; DRUG; DERIVATIVES; HYBRIDIZATION; PREDICTION; INHIBITORS; DISCOVERY; DESIGN;

D O I：

10.1002/ardp.202000077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole-coumarin chalcones and pyrazole-quinoline chalcones were synthesized using multiple-step reactions. All the synthesized compounds were well characterized using different spectroscopic techniques including H-1 and C-13 nuclear magnetic resonance, high-resolution mass spectroscopy, and electrospray ionization-mass spectrometry. The compounds were evaluated for their antitubercular activity against the Mycobacterium tuberculosis H37Rv strain using the microplate Alamar Blue assay, and the minimal inhibitory concentrations (MIC) of the compounds were determined. Among the 32 tested compounds, compounds 3e, 3u, and 7h showed an MIC value of 3.125 mu g/ml, and they were found to be nontoxic. Molecular docking studies of the compounds with the enzyme DprE1 revealed the probable mechanism of action. The chalcone derivatives exhibited binding affinity values between -7.047 and -9.353 kcal/mol. ADME parameters were predicted using the QikProp module of the Schrodinger software, and these compounds exhibited good pharmacological and oral absorption properties.

引用

页数：14

共 39 条

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