Vitthal B Makane1,2, Vagolu Siva Krishna3, Eruva Vamshi Krishna2,4, Manjulika Shukla5, Balakrishnan Mahizhaveni6, Sunil Misra2,4, Sidharth Chopra5, Dharmarajan Sriram3, Vijayan N Azger Dusthackeer6, Haridas B Rode1,2. 1. Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India. 2. Academy of Scientific & Innovative Research, Ghaziabad, Uttar Pradesh 201002, India. 3. Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, RR District, Hyderabad 500 078, India. 4. Department of Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. 5. Department of Microbiology, CSIR-Central Drug Research Institute, Lucknow 226021, Uttar Pradesh, India. 6. Department of Bacteriology, National Institute for Research in Tuberculosis, Chennai, India.
Abstract
AIM: In recent times, heterocyclic chemotypes are being explored for the development of new antimycobacterials that target the drug-resistant tuberculosis. Here, we are disclosing the 5-substitued 2-mercapto-1,3,4-oxadiazoles as potent antitubercular agents. METHODOLOGY: A small library of 2-mercapto-1,3,4-oxadiazoles was synthesized using various acids. The compounds were evaluated for antituberculosis activity against M. tuberculosis H37Rv. RESULTS: Compound 8j was identified as antitubercular lead with MIC of 0.6 μg/ml against M. tuberculosis H37Rv. This compound was nontoxic to CHO-K1 cells and showed selectivity index of 39. Of note, 8j showed antitubercular activity against pre-extensively drug-resistant clinical isolate of Mycobacterium with MIC of 2 μg/ml. CONCLUSION: This study provides potent antitubercular agent which can be further optimized to discover novel antibiotics.
AIM: In recent times, heterocyclic chemotypes are being explored for the development of new antimycobacterials that target the drug-resistant tuberculosis. Here, we are disclosing the 5-substitued 2-mercapto-1,3,4-oxadiazoles as potent antitubercular agents. METHODOLOGY: A small library of 2-mercapto-1,3,4-oxadiazoles was synthesized using various acids. The compounds were evaluated for antituberculosis activity against M. tuberculosis H37Rv. RESULTS: Compound 8j was identified as antitubercular lead with MIC of 0.6 μg/ml against M. tuberculosis H37Rv. This compound was nontoxic to CHO-K1 cells and showed selectivity index of 39. Of note, 8j showed antitubercular activity against pre-extensively drug-resistant clinical isolate of Mycobacterium with MIC of 2 μg/ml. CONCLUSION: This study provides potent antitubercular agent which can be further optimized to discover novel antibiotics.
Authors: Pasupathy Saravanan; V N Azger Dusthackeer; R S Rajmani; B Mahizhaveni; Christy R Nirmal; Sam Ebenezer Rajadas; Neerupma Bhardwaj; C Ponnuraja; Adhin Bhaskar; A K Hemanthkumar; Geetha Ramachandran; Srikanth P Tripathy Journal: Sci Rep Date: 2021-01-13 Impact factor: 4.379