Structural analyses of Spiro-Fused Quinoxaline and Benzoxazine Derivatives as both Antibacterial and Anticancer Agents: Molecular Docking and ADMET Evaluation

Spiro-fused heterocyclic compounds have been widely investigated in medicinal chemistry because of their broad spectrum of pharmacological activities. Two ligands, spiro-fused quinoxaline and spiro-fused benzoxazine were discussed for their antibacterial and anticancer properties by in silico molecular docking studies along with ADMET analysis. Molecular docking was carried out on identified compounds using AutoDock Vina and PyRx against the known antibacterial target aspartyl tRNA synthetase (PDB ID 1l0w) and EGFR kinase (PDB ID 6zj0), a protein involved for progression of cancer growth. Binding affinity of spiro-fused quinoxaline for both proteins (-12.1 kcal/mol and − 10.4 kcal/mol) was found to be higher than that of sprio-fused benzoxazine (-9.2 kcal/mol, and − 8.8kcal/mol), suggesting more potent inhibition ( Table 1,2). PyRx was used to calculate the binding affinities of both (spiro fused quinoxalines and spiro fused benzoxazines) against 1l0w protein i.e., -11.7, -8.7 respectively. ADMET profiling indicated significant pharmacokinetic differences: spiro-fused quinoxaline had low gastrointestinal absorption and could not penetrate the blood-brain barrier, whereas spiro-fused benzoxazine had excellent oral absorption, good BBB penetration, and optimal lipophilicity. Both compounds met Lipinski's rule of five, demonstrating water solubility, synthetic accessibility, and no inhibition of cytochrome P450 enzymes, indicating a low risk of drug-drug interactions. The SwissADME boiled-egg model confirmed that the two ligands had distinct distribution and absorption properties. All of these results show that spiro-fused benzoxazine is a better prospect for future therapeutic research because of its more promising pharmacokinetic characteristics, even if spiro-fused quinoxaline has a higher binding affinity. Together, these results highlight the need for spiro-fused quinoxaline derivatives to undergo structural optimization in order to balance efficacy and bioavailability, ultimately advancing these heterocycles as possible therapies.