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Antioxidative and antiproliferative activities of novel pyrido[1,2-a]benzimidazoles

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Abstract

A series of pyrido[1,2-a]benzimidazoles has been designed, and novel examples are synthesized and evaluated for their potential antiproliferative activity against four human tumour cell lines—cervical (HeLa), colorectal (SW620), breast (MCF-7) and hepatocellular carcinoma (HepG2). In addition, their antioxidative potency has been evaluated by in vitro spectrophotometric assays. Preliminary structure–activity relationships among the synthesized compounds are discussed. Evaluation of their antioxidative capacity has shown that two compounds (25 and 26) possess promising reducing characteristics and free radical scavenging activity. Selective antiproliferative effect in the single-digit micromolar range was observed for compound 25 on MCF-7 \((\hbox {IC}_{50} = 6\,{\upmu }\hbox {M})\) and HeLa \((\hbox {IC}_{50} = 8\,{\upmu }\hbox {M})\) cell lines, comparable to the standards 5-fluorouracil and cisplatin. The combination of the radical scavenging activity and antiproliferative activity of compound 25 positions this compound as a potential lead candidate for further optimization.

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Acknowledgments

We greatly appreciate the financial support of the Croatian Ministry of Science Education and Sports (Project 125-0982464-1356), the Croatian Science Foundation under the project 5596 (Synthesis and cytostatic evaluations of novel nitrogen heterocycles library) and University of Rijeka research Grant 13.11.1.1.11.

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Authors and Affiliations

  1. Laboratory for synthesis and processes of self-assembling of organic molecules, Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia

    Martina Tireli

  2. Department of Animal Husbandry, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000, Zagreb, Croatia

    Kristina Starčević

  3. Department of Biotechnology, Centre for high-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000, Rijeka, Croatia

    Tamara Martinović & Sandra Kraljević Pavelić

  4. Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P. O. Box 177, 10000, Zagreb, Croatia

    Grace Karminski-Zamola & Marijana Hranjec

Authors
  1. Martina Tireli
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  2. Kristina Starčević
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  3. Tamara Martinović
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  4. Sandra Kraljević Pavelić
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  5. Grace Karminski-Zamola
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  6. Marijana Hranjec
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Correspondence to Marijana Hranjec.

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Tireli, M., Starčević, K., Martinović, T. et al. Antioxidative and antiproliferative activities of novel pyrido[1,2-a]benzimidazoles. Mol Divers 21, 201–210 (2017). https://doi.org/10.1007/s11030-016-9702-y

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  • DOI: https://doi.org/10.1007/s11030-016-9702-y

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