Microwave-assisted organic synthesis, antimycobacterial activity, structure–activity relationship and molecular docking studies of some novel indole-oxadiazole hybrids

ABSTRACT

Multidrug-resistant tuberculosis (MDR-TB) is a severe threat to mankind because most drugs are ineffective in inhibiting tubercular strains. Due to the increase of MDR-TB, many first and second-line drugs are ineffective against tubercular strains. To combat the resistance of currently accessible drugs, structural changes must be made on a regular basis. Thus, in the search for new antimycobacterial drugs, a series of 1-(2-(1H-indol-3-yl)-5-phenyl-1,3,4-oxadiazol-3(2H)-yl)-3-phenylprop-2-en-1-ones (5a-o) have been developed, synthesized, characterized, and screened for antimycobacterial activity. The synthetic approach includes imine generation and cyclization using both conventional and microwave methods to create hybrid molecules with indole and oxadiazole motifs. The set of synthesized compounds have demonstrated some promising activity against tubercular strains of Mycobacterium tuberculosis (ATCC 25177) and M. bovis (ATCC 35734). Compound 5l inhibited M. bovis strain 100% in 10 µg/mL concentration, while compound 5m inhibited M. tuberculosis strain 90.4% in 30 µg/mL concentration. Molecular docking study against mycobacterial enoyl reductase (InhA) could provide well-clustered solutions to the binding modes and affinity for these molecules as compound 5l showed glide score of −12.275 and glide energy of −54.937 kcal/mol.

KEYWORDS:

• Indole
• oxadiazole
• microwave irradiation
• antimycobacterial activity
• molecular docking

Acknowledgements

Authors thank Schrödinger Inc. for GLIDE software to carry out the molecular modelling studies. Authors are also thankful to Priyanka Desai, founder of iScribblers for the linguistic editing of the manuscript. Authors are also grateful to Combi-ChemBio Resource Center, CSIR-National Chemical Laboratory, Pune for providing antitubercular screening data of synthesized molecules.

Disclosure statement

No potential conflict of interest was reported by the author.

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2022.2032333

Additional information

Funding

One of the authors, Prof. Nisheeth C Desai, is thankful to University Grants Commission, New Delhi for awarding BSR faculty fellowship-2019 (No. F18-1/2011 (BSR)) and financial assistant.