In vitro and in silico insights into antimicrobial and anticancer activities of novel imidazo[2,1-b][1,3,4]thiadiazoles

Abstract This study explores the design, synthesis, and evaluation of a novel series of isobenzofuran-based imidazo[2,1-b][1,3,4]thiadiazole derivatives, targeting their antimicrobial and anticancer properties. These compounds integrate the pharmacologically significant 1,3,4-thiadiazole and imidazole moieties, which are known for their potential in drug development, although imidazo[2,1-b][1,3,4]thiadiazole-based drugs are not yet available on the market. Therefore, the aim of this study is to develop novel derivatives that could serve as promising candidates for future therapeutic applications. The derivatives were synthesized in two steps and thoroughly characterized using IR, 1H NMR, 13C NMR, and mass spectrometry. All the derivatives had shown fairly good antimicrobial activity against four microorganisms (Escherichia coli, Staphylococcus aureus, Mycobacterium smegmatis and Candida albicans) with minimum inhibition concentration’s ranging from 0.14 to 0.59 mM. The anticancer activity of the compounds against MCF-7 cell lines showed promising activity, where three derivatives, 3a, 3c and 3d exhibited better inhibition than the standard, cisplatin. The highest anticancer activity was shown by the derivative 3c with an IC50 value of 35.81 μM. Molecular docking was studied to determine the docking poses and binding interaction of the derivatives with the protein bearing PDB: 5BNS and 3ZNR; ADME properties of the derivatives are also inferred which gives insights into the bioavailability. The molecular dynamics simulation of the derivative 3c with HDAC7 protien (PDB: 3ZNR) was evalauted to determine the stability of the interaction between the protein and the ligand.