Synthesis, Structural, Electronic, and Medicinal Characterization of a Thiophene‐Bearing Polycyclic Compound: An Approach to Discover Potential Lead Compounds for Precision Cancer Therapy

ABSTRACT Ethyl 9‐methyl‐7‐(thiophen‐2‐yl)pyrido[3',2':4,5]thieno[2,3‐e][1,2,4]triazolo[4,5‐c]pyrimidine‐8‐carboxylate (V) was synthesized, and its structure was confirmed by x‐ray crystallography. Using density functional theory (DFT) calculations at an B3LYP/6−31G level, we explored the equilibrium geometries of V. Hirshfeld surface, and fingerprint analysis was used to examine the intermolecular interactions in the crystal structure. Charge transport was examined using NBO analysis, and the energy gap ( E g ) and possible nonlinear optical characteristics (NLO). The electron‐deficient and electron‐rich sites of the molecule were identified using molecular electrostatic potential, which provided additional reactivity information. The chemical implications of the molecule were described using contour maps of ELF and LOL. Physiochemical and pharmacokinetic investigations were carried out to evaluate its potential as a therapeutic candidate. To ascertain its capacity to interact with biological membranes and targets, physicochemical parameters like molecular weight, lipophilicity (log P), solubility, acidity/basicity (pKa), ADME profile, toxicity, and metabolic transformation were assessed. Moreover, the molecular docking and molecular dynamics simulation were performed to determine the binding affinity, interactions, and structural stabilities with selected targets to determine its anticancer potential. This computational approach predicted binding energy and identified key interactions between the ligand and target substrate, providing valuable insights into the binding mechanism and guiding further optimization and experimental validation.