A convergent multicomponent synthesis, spectral analysis, molecular modelling and docking studies of novel 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione derivatives as potential anti-cervical cancer agents

Abstract

A series of Novel hybrid 3,3-dimethyl-13-(substituted-phenyl)-3,4,5,13-tetrahydro-1H-pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline-1,12(2H)-dione derivatives were designed and chemically synthesized in useful yields. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, 1H, 13C NMR, Mass spectral) analyses, and biologically screened in-vitro for their anti-cervical cancer activity against HeLa cancer cell line. The results of cytotoxic evaluation indicated that compounds 7a, 7b, 7c and 7e were appeared to have broad-spectrum cytotoxic activity with IC50 values of 270 µM, 320, 330, and 400 µM, against HeLa cell line. Compound 7a exhibited the most promising inhibitory activity against HeLa cell line as compared to 7b, 7c and 7e. Structural-Activity Relationship (SAR) results show that the presence of electron withdrawing substituents play an important role in the anti-cervical cancer activity of these tested compounds. Moreover, molecular docking studies were conducted to investigate the probable binding conformations of these anti-cancer agents and in-silico ADME (Absorption, Distribution, Metabolism, and Excretion) properties were calculated to predict physicochemical, lipophilicity, pharmacokinetics and medicinal properties of the target compounds.