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Synthesis of azabicyclo[4.2.0]octa-1,3,5-trien-8-one analogues of 1H-imidazo[4,5-c]quinoline and evaluation of their antimicrobial and anticancer activities

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Abstract

In search of new and efficient antimicrobial and anticancer agents based on the imidazoquinoline structural framework, a series of novel 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-ones (8a–f) were synthesized from the corresponding 2,4-dihydroxoquinoline derivative through multistep reactions. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectral studies. The 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) analogues were evaluated for their in vitro antimicrobial activity by serial dilution method minimum inhibitory concentration (MIC). The derivatives 8c, 8e and 8f exhibited excellent antibacterial activity comparable to the parent drug ampicillin with MIC value. Compounds 7a–f and 8a–f were also assessed for their cytotoxic activity (IC50) against HeLa cells using the Trypan blue exclusion assay method. The compounds 7c and 8b displayed potential anticancer activity. In a molecular docking study, these compounds showed minimum binding energy and good affinity towards the active pocket. They are believed to be good inhibitors of β-tubulin. The results of these studies provided evidence that 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) derivatives are a promising class of antibacterial and anticancer agents.

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Acknowledgments

Authors are grateful to the management of SeQuent Scientific LTD, New Mangalore, India for their invaluable support and allocation of resources for this work. Authors are also thankful to late Prof. A. Srikrishna IISc Bangalore, India for providing spectral analysis. We are also thankful Prof. H-Kun Fun for the single crystal study of the compound.

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Authors and Affiliations

  1. Department of Studies in Chemistry, Mangalore University, Mangalagangothri, 574199, Karnataka, India

    Reshma Kayarmar, G. K. Nagaraja & Manjunath Bhat

  2. SeQuent Scientific Limited, No. 120 A & B, Industrial Area, Baikampady, New Mangalore, 575011, Karnataka, India

    Reshma Kayarmar, G. K. Nagaraja, Manjunath Bhat & T. Arulmoli

  3. Department of Bioscience, Mangalore University, Mangalagangotri, 574199, Karnataka, India

    Prashantha Naik

  4. Department of P.G. Studies and Research in Biotechnology and Bioinformatics, Kuvempu University, Shankaraghatta, 577 451, Karnataka, India

    K. P. Rajesh

  5. B.C. Road Clinical Laboratory, Kaikamba, B.C. Road, 574219, Karnataka, India

    Suchetha Shetty

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  1. Reshma Kayarmar
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  2. G. K. Nagaraja
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Correspondence to G. K. Nagaraja.

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Kayarmar, R., Nagaraja, G.K., Bhat, M. et al. Synthesis of azabicyclo[4.2.0]octa-1,3,5-trien-8-one analogues of 1H-imidazo[4,5-c]quinoline and evaluation of their antimicrobial and anticancer activities. Med Chem Res 23, 2964–2975 (2014). https://doi.org/10.1007/s00044-013-0885-9

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  • DOI: https://doi.org/10.1007/s00044-013-0885-9

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