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Design, synthesis, in vitro and in silico anti-cancer activity of 4H-chromenes with C4-active methine groups

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Abstract

A combinatorial library of eighteen C4-active methine-substituted 4H-chromenes were synthesized, and their anti-cancer properties were evaluated against four human cancer cell lines, namely laryngeal carcinoma (Hep2), lung adenocarcinoma (A549), colon carcinoma (HT-29) and cervical cancer (HeLa). Out of them, six displayed significant anti-proliferative activity. The best among them, the 4H-chromene with C4-malononitrile substitution, was selected for further structure–activity relationship studies. Six analogues were synthesized and subjected to in vitro studies on above four cancer cell lines. The best among them was subjected to detail in silico studies by binding with Bcl-2 protein, and the results corroborated those obtained from in vitro studies. Our findings show that the C4-malononitrile and C2-N-phenyl-substituted 4H-chromene are the most promising lead molecules for treatment of cancer.

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Acknowledgments

AP thanks Pondicherry University for fellowship. JM (09/559/(0076)/2011/EMR-1, dated 30-3-3011), and MK (09/559/(0100)/2013/EMR-I, dated 16-3-2013) thank the Council of Scientific and Industrial Research (CSIR) for Senior Research Fellowship (SRF). RK and JM thank the Centre for Bioinformatics (Funded by Department of Biotechnology and Department of Information Technology, New Delhi, India) and Pondicherry University for providing the computational facilities to carry out the research work. HSPR thank the UGC for the Special Assistance Programme (SAP) and the Department of Science and Technology (DST) for the Fund for Improvement of S&T Infrastructure in Higher Educational Institutions (FIST). Authors also thank “Interdisciplinary Programme of Life Sciences for Advanced Research and Education” (IPLS) funded by DBT, India and Central Instrumentation Facility, Pondicherry University for support and spectra.

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Authors and Affiliations

  1. Department of Chemistry, School of Physical, Chemical and Applied Sciences, Pondicherry University, Puducherry, 605 014, Puducherry, India

    A. Parthiban & H. Surya Prakash Rao

  2. Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, 605 014, Puducherry, India

    M. Kumaravel & R. Rukkumani

  3. Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry, 605 014, Puducherry, India

    J. Muthukumaran & R. Krishna

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  1. A. Parthiban
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  4. R. Rukkumani
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  5. R. Krishna
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  6. H. Surya Prakash Rao
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Correspondence to R. Rukkumani, R. Krishna or H. Surya Prakash Rao.

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Dedicated to late Professor A. Srikrishna, Indian Institute of Science, Bengaluru, India.

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Parthiban, A., Kumaravel, M., Muthukumaran, J. et al. Design, synthesis, in vitro and in silico anti-cancer activity of 4H-chromenes with C4-active methine groups. Med Chem Res 24, 1226–1240 (2015). https://doi.org/10.1007/s00044-014-1190-y

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