Synthesis, in Silico Therapeutic Target Screening Studies of Benzothiazolo[3,2‐a]Chromeno[4,3‐d]Pyrimidin Pharmacophore

ABSTRACT The sustainable one‐pot multicomponent reaction between substituted aromatic aldehyde, 2‐aminobenzothiazole, and 4‐hydroxycoumarin molecules using β‐Cyclodextrin as an organocatalyst to synthesize benzothiazolo[3,2‐a]chromeno[4,3‐d]pyrimidin derivatives in excellent yield with short reaction time. Chiral HPLC analysis of representative products (4o) confirmed racemic mixtures (ee ≈ 63%). β‐Cyclodextrin is found to be a highly efficient and recyclable exterior‐surface catalyst, enhancing substrate solubility and organization in aqueous media without imparting stereoselectivity. Further, the antibacterial activity of the newly synthesized derivatives (4a–4t) was evaluated against both Gram‐positive ( Staphylococcus aureus ) and Gram‐negative bacteria ( Pseudomonas aeruginosa and Escherichia coli ). Among these, compound 4n demonstrated the highest potency, with a minimum inhibitory concentration (MIC) of 39 µM against S. aureus . Activity against Gram‐negative strains was comparatively lower, likely due to the reduced permeability of their outer membrane. These findings indicate that compound 4n exhibits promising bacteriostatic activity selectively against Gram‐positive pathogens. The most plausible therapeutic target of the synthesized compounds was identified through an in silico pharmacophore‐guided target identification approach, and a potential molecular mechanism underlying their bacteriostatic activity has been proposed.