Design, synthesis, DFT, molecular docking, POM analysis and anticancer for prostate cancer cells of new sulfonamide...

A series of imidazole [1,2-a] pyridine sulfonamide derivatives was designed and synthesized starting from 2-aminopyridine. In first step, 2-amino pyridine was reacted with 4-bromo phenacyl bromide in the presence of MgO leading to the afford the corresponding imidazole [1,2-a] pyridine scaffold (Panda et al., 2022 [1]). This intermediate was subsequently subjected to chlorosulfonation using chlorosulfonic acid to afford imidazo [1,2-a] pyridine -3- sulfonyl chloride (Amer, 2009 [2]). Thereafter, derivative (Amer, 2009 [2]) was treated with a variety of drugs containing an amine group [4-amino-5-chloro-N-(2- (diethyl amino) ethyl) -2-methoxy benzamide, 4-amino -N-(pyridin-2-yl) benzene sulfonamide and 4-(amino methyl) cyclohexane -1-carboxylic acid] via the classical grand method, resulting in the synthesis of the desired imidazole [1,2-a] pyridine sulfonamide derivatives [A1, A2 and A3]. All synthesized compounds were characterized using FTIR, ¹HNMR and ¹³CNMR to confirm their structure. In order to understand their molecular properties and biological behavior, computational studies including density functional theory (DFT), molecular electrostatic potential (MEP), Petra Osiris Molinspiration (POM) analysis, and molecular docking, provides an atomic-level explanation for the molecular behavior of the derivatives being tested for new sulfonamide on the prostate cancer (PDB ID: 5JJM). The docking results are predictive in nature and suggest favorable binding interactions, especially for compound A2. In vitro, the cytotoxic effect of [A1, A2 and A3] were evaluated experimentally on human prostatic adenocarcinoma cell line (PC3) with human dermalfibroblasts (HdFn) as the normal cell line using MTT assay for (24, 48 and 72) hours. Furthermore, derivative A2 showed the lowest PC3 IC₅₀ after 72 h (49.77 μM) and the highest selectivity index at the time (5.77).