Synthesis and antimicrobial activity of substituted 1,4--spiro[benzocycloheptene-6(5),3′(3-pyrazol)-5-one]-benzene under microwave irradiation and molecular docking study

Background and objective
Spiropyrazole derivatives are one of the most bioactive spiro compounds that play a vital role in drug discovery, such as antibacterial, anti-inflammatory, antifungal, antiviral, analgesic, and antidepressant activities. Moreover, microwave as an energy source enhances the reaction rates and improves the regioselectivity. The aim of this study was to synthesize the spiropyrazole derivative compounds. Molecular docking was performed.
Materials and methods
1,3-Dipolar cycloaddition of 6,6′-(1,4-phenylene-(methanylylidene))-(6,7,8,9-tetrahydro-5-benzo[7]annulen-5-one) to a variety of nitrilimines (generated by triethylamine dehydrohalogenation of the corresponding hydrazonoyl halides) under microwave irradiation proceeded regioselectively affording spiro[benzo[7]-annulene-6,3′-pyrazol]-4′-yl)phenyl)-spiro[benzo[7]annulene-6,3′-pyrazol]-5(7)-ones. The structure of the newly synthesized compounds was confirmed on the basis of spectral data and elemental analyses. The antimicrobial activity of the (spiropyrazoles) derivatives was tested for antimicrobial activity. Molecular docking was performed and analyzed with the molecular modeling environment program.
Results and conclusion
Compound has high potency against all fungi (except ) and bacterium species (except ) compared with the reference drug fungicide amphotericin B and the standard bactericides ampicillin and gentamicin. Docking of the most active antibacterial compounds and against the dihydropteroate synthase enzyme gave comparable scores for hydrogen bond interaction (−22.9123, −17.5995 kcal/mol(and binding mode to the reference antibiotic sulfamethoxazole (−13.00 kcal/mol).