Design, Synthesis and Biological Evaluation of Novel Antitubercular Agents by Combining Pyrazoline and Benzoxazole Pharmacophores  

作　　者：Hemal M. Soni Popatbhai K. Patel Mahesh T. Chhabria Ashish K. Patel Dharmraj N. Rana Pathik S. Brahmkshatriya Hemal M. Soni;Popatbhai K. Patel;Mahesh T. Chhabria;Ashish K. Patel;Dharmraj N. Rana;Pathik S. Brahmkshatriya(M/S Piramal Enterprises Ltd., Piramal Discovery Solutions, Plot No. 18, Pharmaceutical Special Economic Zone, Village Matoda, Ta. Sanand, Ahmedabad, India;M.G. Science Institute, Opp. Gujarat University, Navrangpura, Ahmedabad, India;Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, India;Oxygen Healthcare Res. Pvt. Ltd., Plot No. 35, Panchratna Industrial Estate, Near IBP Laxminarayan Petrol Pump, Changodar, Ahmedabad, India)

机构地区：[1]M/S Piramal Enterprises Ltd., Piramal Discovery Solutions, Plot No. 18, Pharmaceutical Special Economic Zone, Village Matoda, Ta. Sanand, Ahmedabad, India [2]M.G. Science Institute, Opp. Gujarat University, Navrangpura, Ahmedabad, India [3]Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, India [4]Oxygen Healthcare Res. Pvt. Ltd., Plot No. 35, Panchratna Industrial Estate, Near IBP Laxminarayan Petrol Pump, Changodar, Ahmedabad, India

出　　处：《International Journal of Organic Chemistry》2016年第3期157-176,共20页有机化学国际期刊（英文）

摘　　要：Various recent reports on Tuberculosis have alarmed an increase in the patient class and subsequent death rates across the globe. Over and above the spread of more dangerous and fatal forms of tuberculosis like MDR-TB i.e. multiple-drug resistance tuberculosis, XDR-TB i.e. extensively-drug resistance tuberculosis & TDR-TB i.e. total-drug resistance tuberculosis has forwarded an urgent need to discover novel antitubercular agents. The current work is aimed at combining two previously well-known pharmacophores (pyrazoline and benzoxazole nucleus) in order to design and synthesize a series of novel benzoxazole-based pyrazoline derivatives. The synthesized target compounds were structurally confirmed by LCMS, 1H-NMR and 13C-NMR analysis. The target compounds were In vitro evaluated against M. tuberculosis H37Rv strain, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. The In vitro screening results depicted that majority of the target compounds displayed potent activity with MIC in a range of ~0.8 to 6.25 μg/mL. Many compounds were found to be more potent than isoniazid against MDR-TB with MIC value 3.12 μg/mL and XDR-TB with MIC value 12.5 μg/mL. Cytotoxicity assay of these active compounds on VERO cell lines also displayed good selectivity index.Various recent reports on Tuberculosis have alarmed an increase in the patient class and subsequent death rates across the globe. Over and above the spread of more dangerous and fatal forms of tuberculosis like MDR-TB i.e. multiple-drug resistance tuberculosis, XDR-TB i.e. extensively-drug resistance tuberculosis & TDR-TB i.e. total-drug resistance tuberculosis has forwarded an urgent need to discover novel antitubercular agents. The current work is aimed at combining two previously well-known pharmacophores (pyrazoline and benzoxazole nucleus) in order to design and synthesize a series of novel benzoxazole-based pyrazoline derivatives. The synthesized target compounds were structurally confirmed by LCMS, 1H-NMR and 13C-NMR analysis. The target compounds were In vitro evaluated against M. tuberculosis H37Rv strain, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. The In vitro screening results depicted that majority of the target compounds displayed potent activity with MIC in a range of ~0.8 to 6.25 μg/mL. Many compounds were found to be more potent than isoniazid against MDR-TB with MIC value 3.12 μg/mL and XDR-TB with MIC value 12.5 μg/mL. Cytotoxicity assay of these active compounds on VERO cell lines also displayed good selectivity index.

关 键 词：ANTITUBERCULAR BENZOXAZOLE PYRAZOLINE PHARMACOPHORE Microplate Alamar Blue Assay 

分 类 号：O62[理学—有机化学]