Multicomponent synthesis of novel imidazole-pyran derivatives: in silico and in vitro studies

Herein, a three-component reaction was used for the synthesis of imidazole-pyran derivatives (4a-n) through the reaction between imidazol-5-carbaldehyde (1a-n), malononitrile (2), and methyl acetoacetate (3). The reaction process was simple, quick, proceeded without the need for any purification technique and used green solvents. The synthesized substances (4a-n) were evaluated for their potential anticancer effects on the MCF-7 (breast cancer), HT29 (colon cancer), and A2780cis (cisplatin-resistant ovarian cancer) cell lines, and a control normal cell line, CHO (Chinese hamster ovary). Notably, compounds 4e and 4h demonstrated pronounced effects on the MCF-7 cell line, with an IC₅₀ value of 11.74 ± 0.17 µM and 9.44 ± 0.17 µM, respectively. Compounds 4e and 4h also showed appropriate toxicity in the HT-29 and A2780cis cell lines. These two compounds (4e and 4h) also demonstrated the ability to suppress colony formation and trigger apoptosis in MCF-7 cells. Additionally, in silico studies, such as molecular docking and molecular dynamics, were conducted on VEGFR2. This approach investigated the interaction and binding types of the synthesized compounds in the receptor, their stability, and the change in the protein structure during molecular docking and molecular dynamics.