4‐Thiazolidinone Derivatives as PARP‐1 Inhibitors Targeting Breast Cancer: Integrating DFT, Molecular Docking, Molecular Dynamics Simulations, and ADMETox Analysis

ABSTRACT Heterocyclic compounds are well known for their immense biomedical applications and are thus widely explored by researchers and scientists all over the world for their use as a benefit to mankind. Herein, an overarching computational and theoretical analysis of the designed thiazolidin‐4‐one derivatives with potential anti‐breast cancer activity is presented, employing molecular docking, quantum chemical calculations (DFT, FMO), ADMETox, and molecular dynamic simulation approaches. An in‐silico approach was used to analyze the binding affinities of a series of novel substituted 4‐thiazolidinones against Poly (ADP‐ribose) polymerase‐1(PARP‐1), a key therapeutic target for breast cancer, more likely triple‐negative breast cancer (TNBC). In the present work, thirty‐two 4‐thiazolidinone derivatives were designed based on available literature, to develop agents with therapeutically greater efficacy against breast cancer and minimal adverse effects. The molecular structures were optimized using density functional theory (DFT). The molecular docking analysis of the 4‐thiazolidinone series with the protein PARP‐1, revealed better interaction affinities of most of the molecules within the binding pocket as compared to the co‐crystallized ligand olaparib. Among the docked derivatives, compound 3c exhibited the highest interaction affinity toward PARP1 with binding energy value of −253.785 kcal/mol.