Regioselective synthesis, structural investigation and binding behavior of 6-aroyl-7-aryl-5-methyl-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidines with BSA using various spectroscopic and in silico methods

Abstract

A series of 6-aroyl-7-aryl-5-methyl-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidines 5 was synthesized regioselectively via a one-pot multicomponent reaction between β-diketone 1, aromatic aldehyde 2, and 3-amino-1H-1,2,4-triazole 3. The regioisomeric structure of the newly synthesized compounds 5 was unambiguously determined using ¹H NMR, ¹³C NMR, and rigorous multinuclear 2D-NMR spectroscopy [¹H–¹³C] HMBC, [¹H–¹³C] HSQC and [¹H–¹⁵N] HMBC. The remarkable features of this protocol are high yields, operational simplicity, use of commercially available reagents and broad substrate scope. The interactions of selected compounds (5f, 5m and 5t) with bovine serum albumin (BSA) were studied by UV-vis spectroscopy, steady-state fluorescence, and molecular docking. The results indicated that compound 5t could effectively quench the intrinsic fluorescence of BSA via a static quenching process. Competitive binding studies using site markers demonstrated that compound 5t binds to site I of BSA. Binding constants for [1,2,4]triazolo[1,5-a]pyrimidines show that the affinity of 5t binding to BSA is stronger than that of 5f and 5m.