Novel diaryl dihydropyrimidines as promising anticancer agents: In silico, in vitro investigation

Due to the structural resemblance with the nucleic acid bases, Dihydropyrimidines (DHPs) gained a special attention for exploring for chemotherapeutic agents. Diaryl dihydropyrimidines (DADPs) were reported to have anticancer properties and antiviral and antibacterial activities. In an attempt to design new DADP compounds, we have come up with some novel compounds (3a–3o, 4a–4o, 5a–5o) by incorporating the piperonal to check its significance on biological activity. Initially, computational screening has been performed to shortlist the top molecules which are showing better binding interactions with the selected targets of cancer treatment such as VEGFR2, JAK1 kinase, and JAK3 kinase. Later the selected compounds were synthesized (15 compounds) and characterized by spectral analysis. In the in vitro anti-proliferative activity in the three cell lines, it was observed that the compounds have exhibited potential biological activity (IC 50 values 3d – 42.67 ± 2.28 μM against MCF-7; 3n – 59.68 ± 2.81 μM against Hep G-7; 3d – 70.64 ± 3.12 μM against A-549). It was observed that the piperonal, substituted phenyl ring, secondary amine in mannich base has resulted with improved biological activity, the same has been observed in molecular docking studies.