Synthesis, Docking Study, and Antimicrobial Activity of Some New Heterocyclic Compounds Bearing Naphthalene Moiety

Abstract

Abstract Upon reaction with α,β‐unsaturated nitriles (2 a – d) and/or salicylaldehyde, 3‐(naphthalen‐2‐yl)‐3‐oxopropanenitrile (1) yields pyridine derivatives 3 a – d and/or the imino chromene derivative 4 . Compound 1 reacted with phenyl isothiocyanate in a basic medium to give the intermediate potassium salt 6 . Upon stirring at room temperature, the intermediate 6 with some α‐halogenated compounds yielded the acyclic compounds 7 , 9 , 11 , 13 , and 15 . On the other hand, refluxing intermediate 6 with the same α‐halogenated compounds in DMF in the presence of TEA afforded the corresponding thiophene derivatives 8 , 10 , 12 , 14 , and 16 . The reaction of thiol 17 with hydrazine hydrate derivatives 18 a – d yielded the corresponding pyrazole derivatives 21 a – d . Compound 20 reacted with o ‐phenylenediamine or o ‐aminothiophenol in the presence of DMF/TEA to give the corresponding benzothiazole or benzoimidazole derivatives 27 a and 27 b , respectively. Thirty new synthesized compounds were examined for their antibacterial activity against Gram‐positive bacteria including S. aureus and B. subtilis , Gram‐negative bacteria such as P. aeruginosa and E. coli , and yeast‐like fungi like C. albicans in vitro . Compounds 15 , 16 , 21 d , 27 a , 27 b , exhibited the highest antibacterial activity against Gram‐positive bacteria. Molecular docking experiments were conducted to explore the binding affinities and interaction modalities of selected derivatives with the target PDB‐3cmt protein.