Anticancer activity and morphological analysis of Pt (II) complexes: Their DFT approach, docking simulation, and ADME‐Tox profiling

A consistent series of Pt (II) polypyridyl complexes (i.e., LDP‐10–25 ), previously obtained and characterized by our research group, underwent extensive biological investigations to verify their activity profile as target‐based anticancer agents. Preliminary in vitro screening at 10 μM against three tumor cell lines known to overexpress DNA G‐4 (MDA‐MB 231, U87, and U2‐OS) pointed out that four of them, namely, LDP‐15 , LDP‐16 , LDP‐24 , and LDP‐25 , had promising cytotoxic activity compared with cisplatin. Therefore, these four compounds were selected for continuous assays against the same three cell lines and morphological analyses on U2‐OS cells that showed IC 50 values in the micromolar range and remarkable changes in nuclei shape and cytoskeleton integrity, respectively. Docking studies supported the idea that the antiproliferative activity of the complexes could be attributed to their interaction via a hybrid binding mode with the intended molecular target, DNA G‐4. In addition, in silico ADME‐Tox profiling studies showed no risk of tumorigenic, irritant, or reproductive effects for the title compounds. DFT calculations were used to verify the structural characteristics of the four selected compounds and to investigate their electronic behavior. Overall, the results obtained, both experimentally and theoretically, indicate that LDP‐15 , LDP‐16 , LDP‐24 , and LDP‐25 complexes could be useful for further study as potential therapeutic agents.