Synthesis, evaluation and CoMFA/CoMSIA study of nitrofuranyl methyl N-heterocycles as novel antitubercular agents. Issue 8 (1st May 2018)

• Record Type: Journal Article
• Authors: Wang, Apeng; Yang, Yang; Jun, Yangsheng; Wang, Bin; Lv, Kai; Liu, Mingliang; Guo, Huiyuan; Lu, Yu
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 8(2018)
• Page Start: 2073
• Page End: 2084
• Publication Date: 2018-05-01
• Subjects: Antitubercular agents -- Nitrofuranyl methyl N-heterocycles -- CoMFA/CoMSIA analysis -- 3D-QSAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.03.004
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of novel nitrofuranyl methyl N-heterocycles based on the structure of IIIM-MCD-211 were designed and synthesized. Compounds 6d, 8b and 12a show excellent activity against MTB H37Rv strain (MIC: 0.031–0.062 μg/mL) roughly comparable to INH and IIIM-MCD-211. In addition, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on the above mentioned chemical series employing comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques. The developed CoMFA and CoMSIA models display high external predictability (r 2 pred of 0.954 and 0.935, respectively) and good statistical robustness. More importantly, the newly designed compounds 16a and 16b (MIC: <0.016 μg/mL) based on the two models, as expected, were found to be more active than 12a and IIIM-MCD-21. Design and synthesis of more potent nitrofuranyl methyl N-heterocycles as anti-TB agents are currently in progress.