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Diazabenzo[a]phenoxazone sulphonamides: synthesis, in-silico and in-vitro antimicrobial studies

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Abstract

The syntheses of new sulphonamide derivatives of 8,10-diazabenzo[a]phenoxazones are reported. The condensation of 4,5-diamino-6-hydroxy-2-mercaptopyrimidine and 2,3-dichloro-1,4-naphthoquinone in a basic medium gave the key functional intermediate, 11-amino-6-chloro-9-mercapto-8,10-diazabenzo[a]phenoxazin-5-one. The conversion of the later compound to its sulphonamide derivatives was achieved via nickel catalyzed cross-coupling Buchwald-Hartwig protocol. Reaction between 11-amino-6-chloro-9-mercapto-8,10-diazabenzo[a]phenoxazin-5-one and various aryl sulphonamides and sulphonyl chlorides furnished eight new mono sulphonamide substituted diazaphenoxazone compounds. Subsequent coupling of mono sulphonamide substituted diazaphenoxazone compounds 5a-d with four different arylsulphonyl chlorides under similar reaction conditions gave the disubstituted derivatives 8a-d. The products were isolated in 74 – 88% yields and characterized by means of Uv-visible, FT-IR, 1H-NMR, 13C-NMR, and Mass spectroscopy. The synthesized compounds were screened for antimicrobial activity against bacterial strains: Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhi and Klebsiella pneumonia, and fungal strains, Aspergillus niger, and Candida albican, using agar-well diffusion method. The activities of the compounds were compared with that of colymycin, which is a strong antibacterial, and antifungal drug, Most of the compounds showed appreciable antimicrobial activities comparable with the activity of colymycin. The in silico study revealed that all the synthesized compounds showed significant binding affinity for both intact and mutated DNA gyrase. Compounds 8a and 5b showed the highest binding affinities of -12.31 and -13.30 kcal/mol for intact and mutated DNA gyrase respectively.

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Authors and Affiliations

  1. Department of Pure & Industrial Chemistry, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria

    Mercy A. Ezeokonkwo & Efeturi A. Onoabedje

  2. Natural Science Unit, School of General studies, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria

    Cosmas C. Eze & Fidelia N. Ibeanu

  3. Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria

    Sunday N. Okafor

  4. Department of Chemistry, Gregory University, Uturu, Abia State, Nigeria

    Evelyn U. Godwin-Nwakwasi

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  1. Mercy A. Ezeokonkwo
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  2. Cosmas C. Eze
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Correspondence to Mercy A. Ezeokonkwo.

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Ezeokonkwo, M.A., Eze, C.C., Okafor, S.N. et al. Diazabenzo[a]phenoxazone sulphonamides: synthesis, in-silico and in-vitro antimicrobial studies. Med Chem Res 27, 2482–2493 (2018). https://doi.org/10.1007/s00044-018-2251-4

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