Synthesis of novel bis-(1,3,4-oxadiazol-2-ylamino)-2-aryl-1,3-thiazolan-4-ones as antimicrobial, nematicidal and anticancer agents

A series of novel bis-heterocycles, 3-(5-[2-methoxy-5-(4-methoxy-3-5-[(4-oxo-2-(aryl/hetaryl) -1,3-thiazolan -3-yl) amino]-1,3,4-oxadiazol-2-ylbenzyl)phenyl]-1,3,4-oxadiazol-2-ylamino)-2-(aryl/hetary1)-1,3-thiazolan-4-ones 8a-j have been synthesized by simple and high yield routes. Structures of all the newly synthesized compounds have been established by their spectral data and elemental analysis, and they have been evaluated for their in vitro antimicrobial, nematicidal and anticancer activities. Among the tested compounds, those with 4-chlorophenyl (8c), 3-nitrophenyl (8d) and 2,4-difluorophenyl (81) substituents at 2-position of thiazolidinone ring are found to be potent antibacterial and antifungal agents. Exploration of nematicidal activity of compounds 8a-j reveal that, compounds 8f, 8i and 8j bearing 2,4-difluorophenyl, 2-furyl and 1,3-benzodioxole substituents respectively at 2nd position of thiazolidinone ring show prominent activity comparable to the standard levamisole and have emerged as potential nematicidal agents. In vitro anticancer activity assay reveals that the compounds with electron-withdrawing groups viz., 4-chlorophenyl (8c), 3-nitrophenyl (8d) and 2,4-difluorophenyl (8f) display significant activity which is more than the standard against A549 (lung cancer) cell line, and compounds bearing electron-donating groups such as 4-methylphenyl (8b), 4-hydroxyphenyl (8e), N,N-dimethylaminophenyl (8g), and 4-methoxy-3-hydroxyphenyl (8h) show superior/comparable potency to the standard against MDAMB-231 (breast cancer) cell line. The docking scores estimated by Schrodinger software also correlate well with the experimental anticancer activity.