Thiazolyl-pyrazole derivatives as potential antimycobacterial agents

  • Bioorg Med Chem Lett. 2019 May 15;29(10):1199-1202. doi: 10.1016/j.bmcl.2019.03.020.
Sushma J Takate  1 ,  Abhijit D Shinde  2 ,  Bhausaheb K Karale  3 ,  Hemant Akolkar  3 ,  Laxman Nawale  4 ,  Dhiman Sarkar  4 ,  Pravin C Mhaske  5
Affiliations
  • 1. Department of Chemistry and Research Centre, New Arts, Commerce and Science College, Ahmednagar 414001, India. Electronic address: [email protected].
  • 2. Department of Chemistry, S. P. Mandali's Sir Parashurambhau College, Tilak Road, Pune 411 030, India.
  • 3. Department of Chemistry, Rayat Shikshan Santhsa's Radhabai Kale Mahila Mahavidyalya, Ahmednagar 414001, India.
  • 4. CombiChemBio Resource Centre, National Chemical Laboratory, Pune 411 008, India.
  • 5. Department of Chemistry, S. P. Mandali's Sir Parashurambhau College, Tilak Road, Pune 411 030, India. Electronic address: [email protected].
PMID: 30910461 DOI: 10.1016/j.bmcl.2019.03.020
Abstract

Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. A series of thiazolyl-pyrazole derivatives (6a-f, 7a-f, 8c, 8e) were screened for antimycobacterial activity against dormant M. tuberculosis H37Ra (D-MTB) and M. bovis BCG (D-BCG). Nine thiazolyl-pyrazole analogs, 6c, 6e, 7a, 7b, 7c, 7e, 7f, 8c and 8e exhibited promissing minimum inhibitory concentration (MIC) values (0.20-28.25 µg/mL) against D-MTB and D-BCG strains of Mtb. Importantly, six compounds (7a, 7b, 7e, 7f, 8c and 8e) exhibited excellent antimycobacterial activity and low cytotoxicity at the maximum evaluated concentration of >250 µg/mL. Finally, the promising antimycobacterial activity and lower cytotoxicity profile suggested that, these compounds could be further subjected for optimization and development as a lead, which could have the potential to treat tuberculosis.

Keywords
Antimycobacterial activity; Cytotoxicity; Pyrazole; Thiazoles.