Synthesis, antimicrobial evaluation, molecular docking, and drug-likeness assessment of novel phenothiazine chromene hybrid compounds

Abstract

By carefully hybridizing with scaffolds generated from chromene, pyranochromene, and cyanoacetamide, a novel class of phenothiazine-based heterocycles was created. IR, NMR, and MS investigations were used to establish the structural integrity of each molecule. Several derivatives showed considerable inhibitory activity, especially compounds 4, 7, and 10, which had MIC values ranging from 3.9 to 15.6 µg/mL against both Gram-positive and Gram-negative bacteria, according to the antimicrobial assessment. The majority of compounds met Lipinski's criteria, indicating favorable oral bioavailability, according to the drug-likeness assessment. Significant binding affinity was shown by molecular docking against Staphylococcus aureus β-lactamase (PDB: 3G7B). Compound 7 had the best docking score (-5.99 kcal/mol), followed by compound 4 (-5.86 kcal/mol), which was supported by important hydrophobic and hydrogen-bonding interactions with Asp73, Arg76, and Lys103. These findings demonstrate the possibility of phenothiazine-chromene hybrids as viable options for creating novel antimicrobial medicines that effectively combat infections that are resistant to multiple drugs.