Synthesis, in vivo, in silico toxicological evaluation, and safety assessment of novel methyl 4-amino-1,9b-dihydrochromeno[3,4-c] pyrrole-1-carboxylate

Abstract

This study reports the synthesis and comprehensive evaluation of a chromene-based heteroaromatic ester, Methyl 4-Amino-1,9b-Dihydrochromeno[3,4-c] pyrrole-1-carboxylate (DCP). The compound (C₁₃H₁₂N₂O₃; MW 244.25) was obtained as a chocolate-coloured crystalline solid in 51% yield with a melting point above 200 °C. Structural elucidation was achieved using MS, FTIR, and NMR spectroscopy, confirming the presence of N–H, aromatic C = C, C–O, methoxy, and amine functionalities consistent with the proposed structure. Toxicological evaluation in Wistar rats administered graded doses (25–100 mg/kg) for 14 days demonstrated good tolerability, with stable body weights and preserved hepatic and renal function markers. DCP enhanced antioxidant defenses by increasing catalase, superoxide dismutase, and glutathione levels, while reducing malondialdehyde, nitric oxide, and myeloperoxidase activity in liver and kidney tissues. In silico molecular docking revealed moderate binding affinity toward glutathione S-transferase (−6.0 kcal/mol) and inducible nitric oxide synthase (−8.8 kcal/mol), supported by favorable ADMET predictions. Antimicrobial assays showed selective activity against Gram-positive bacteria. DCP demonstrated MIC value of 0.0625 mg/mL against <i>Staphylococcus aureus</i> (SA) and <i>Enterococcus faecalis</i> (EF); 0.125 mg/mL against <i>Pseudomonas aeruginosa</i> (PA) and <i>Bacillus cereus</i> (BC); 0.25 mg/mL against <i>Vibrio cholerae</i> (VC) and Salmonella typhi (ST); and 1.00 mg/mL against multi-resistant <i>Staphylococcus aureus</i> (MRSA). Overall, DCP exhibits promising antioxidant and antimicrobial potential with a favorable safety profile.