Nitrogen-Based Fused Heterocyclic Compounds: Synthesis, Characterization, and Computational Study Profiling

Nitrogen-containing fused heterocyclic compounds are important scaffolds in medicinal chemistry because of their structural versatility and potential biological activities. The present study aimed to synthesise, characterise, and computationally evaluate substituted hexahydroquinoline-3-carbonitrile derivatives as potential anticancer agents targeting the anti-apoptotic protein myeloid cell leukaemia-1 (Mcl-1). The compounds were synthesized through a two-step procedure and characterized using physicochemical parameters, FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry. Molecular docking was performed using MOE software (version 2009.10) with the Mcl-1 protein (PDB ID: 2PQK), while SwissADME and ADMETlab were employed to predict drug-likeness, pharmacokinetic properties, and toxicity profiles. Among the synthesized derivatives, F8 exhibited the most favorable docking score (−16.73 kcal/mol), followed by F7 (−15.09 kcal/mol), compared with gambogic acid (−16.67 kcal/mol). The ADMET predictions indicated that the compounds generally satisfied Lipinski's rule of five and Veber's criteria, with favorable predicted gastrointestinal absorption and preliminary safety profiles. Overall, F7 and F8 emerged as promising computational leads for further investigation of Mcl-1-targeting anticancer activity. Experimental validation through biochemical inhibition assays, cytotoxicity studies, and apoptosis evaluation is required to establish their biological efficacy and therapeutic potential.