Synthesis, In Silico Analysis, Antibacterial, Radical Scavenging and Antidiabetic Activities of Certain Bis-Azetidinones and Bis-Thiazolidinones.

A panel of 1,1-(phenylene)bis[3-chloro-4-(substituted phenyl)azetidin-2-ones] (4a-m) and 3,3′-(1,4-phenylene)bis[2-(substituted phenyl)thiazolidin-4-ones] (5a-m) were synthesized from Schiff base intermediates 3a-m, that were in turn prepared from reaction between p-phenylenediamine and substituted benzaldehydes. The structures of title compounds and intermediates were confirmed by IR, 1H NMR, 13C NMR and mass spectral data. The compounds were screened for antibacterial, DPPH radical scavenging and antidiabetic activities. Compounds 4f and 4a exhibited good antibacterial activity against Gram-positive bacteria, but none showed appreciable activity against Gram-negative bacteria. In DPPH scavenging assay, compounds 5f, 5e and 5a exhibited good activity. Compound 5a displayed highly significant antidiabetic activity in fructose-induced diabetes in rats. The molecular docking studies of bis-thiazolidinones with PPAR-ã revealed the fit with high binding affinity and good interactions. Docking of compound 5a was comparable to the standard drug pioglitazone. The in silico physicochemical, drug-likeness and ADME properties of title compounds were also performed and the majority of them displayed satisfactory results. [ABSTRACT FROM AUTHOR]