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In vitro antimicrobial evaluation and in silico studies of coumarin derivatives tagged with pyrano-pyridine and pyrano-pyrimidine moieties as DNA gyrase inhibitors

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Abstract

Several coumarin-containing substitute nitrogen heterocycles have recently received considerable importance due to their diverse pharmacological properties. One-pot and rapid synthesis of coumarin derivatives was achieved via reactions of acetyl-coumarin with p-chloro-benzaldehyde and malononitrile to provide compound 2-containing cyano-amine using conventional heating. Compound 2 was condensed with different carbon electrophiles triethyl orthoformate, phenyl isocyanate, carbon disulfide, benzoyl chloride, and acetyl chloride that afforded the corresponding chromene derivatives 3–17. All the newly synthesized compounds were characterized by elemental and spectroscopic evidences. All of the synthesized compounds were tested for antimicrobial activity against S. Pneumoniae, S. Epidermidis, S. Aureus, and E. coli as Gram + ve Bacteria, K. Pneumoniae, S. Paratyphi as Gram -ve Bacteria, P. Italicum, A. Fumigatus representative for Fungi. The preliminary screening results showed that most of the compounds had moderate to high activity against all tested organisms. The most potent four compounds were subjected to further investigation against E. Coli DNA gyrase and topoisomerase IV inhibitory activity, and the results showed that all of these derivatives inhibit DNA gyrase and thus cell division. Also, in silico studies were done for the most active compounds which showed good results.

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Acknowedgements

The authors would like to thanks the Research Development Unit and the Central Laboratory at the Faculty of Pharmacy for Girls, Al-Azhar University.

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Authors and Affiliations

  1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, 11754, Cairo, Egypt

    Eman A. Fayed & Samar A. El‑Kalyoubi

  2. Pharmaceutical Medicinal Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, 11754, Cairo, Egypt

    Eman S. Nosseir

  3. Department of Microbiology, Regional Center of Mycology and Biotechnology, Al-Azhar University, Nasr City, Cairo, Egypt

    Ahmed Atef

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Fayed, E.A., Nosseir, E.S., Atef, A. et al. In vitro antimicrobial evaluation and in silico studies of coumarin derivatives tagged with pyrano-pyridine and pyrano-pyrimidine moieties as DNA gyrase inhibitors. Mol Divers 26, 341–363 (2022). https://doi.org/10.1007/s11030-021-10224-4

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