Abstract

Aims: The study aims to synthesize thiocoumarin scaffolds clubbed with pyrimidine and 1,3,4-oxadiazole ring system under microwave irradiation and describe their pharmacological activities.

Background: We report herein an efficient and simple Lewis acid-catalyzed procedure for the synthesis of novel series of thiocoumarin clubbed with pyrimidine and 1,3,4-oxadiazole motifs under microwave irradiation. The microwave-assisted technique has many advantages, such as a higher yield, a clean and selective procedure, shorter reaction time, and simple work-up.

Objective: The objective of the present study is to design and synthesize thiocoumarin scaffolds clubbed with pyrimidine and 1,3,4-oxadiazole ring system by microwave-assisted heating. Our prime focus is to highlight the synthetic approach developed for the synthesis of heterocyclic moieties of pharmacological interest, and the prominence has also been given to distinct advantages provided by microwave heating.

Methods: Thiocoumarin clubbed with pyrimidine, and 1,3,4-oxadiazole motifs was synthesized under microwave irradiation. All the synthesized molecules were evicted by IR, ¹H NMR, ¹³C NMR, and mass spectra. The anti-microbial activity of synthesized compounds was examined against two Gram-negative bacteria (E. coli, P. aeruginosa), two Gram-positive bacteria (S. aureus, S. pyogenes), and three fungi (C. albicans, A. niger, A. clavatus) using the MIC (Minimal Inhibitory Concentration) method, anti-tubercular activity H37Rv using L. J. Slope Method and anti- oxidant activity using DPPH and ABTS bioassay method.

Results: The application of microwave technology for the rapid synthesis of biologically significant thiocoumarin analogues is very promising because of its shorter reaction time and higher yield. Some of these new derivatives showed moderate to good in-vitro anti-bacterial, anti-fungal, and anti-tubercular activity. Compounds B₄ and B₇ appeared to have high radical scavenging efficacies as 35.32 ± 0.446 and 33.97 ± 1.069 μg/mL ± SD of IC50 values in DPPH and ABTS bioassay, respectively.

Conclusion: Microwave-assisted synthesis provides an implicit way to discover a promising class of molecular entities for the development of new anti-microbial and anti-oxidant agents. Oxadiazole and pyrimidine bearing thiocoumarin derivatives showed improved anti-microbial, antitubercular, and anti-oxidant activity.

Keywords: Thiocoumarin, pyrimidine, 1, 3, 4-oxadiazole, anti-microbial, anti-oxidant, anti-tubercular, M. tuberculosis H37Rv, microwave Irradiation.

Graphical Abstract