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

Upon reaction with alpha,beta-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 alpha-halogenated compounds yielded the acyclic compounds 7, 9, 11, 13, and 15. On the other hand, refluxing intermediate 6 with the same alpha-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. The reaction of 2-naphthoyl acetyl nitrile (1) with phenyl isothiocyanate in an alkaline medium afforded the intermediate thiocarbamoyl potassium salt. Refluxing the later intermediate with alpha-halogenated compounds in EtOH/TEA or DMF/TEA afforded thiophene derivatives. On the other hand, stirring at room temperature, the intermediate thiocarbamoyl salt with the same alpha-halogenated compounds in EtOH/TEA afforded their corresponding acyclic compounds. image