2. Academic Validation
  3. Synthesis of DNA interactive C3-trans-cinnamide linked β-carboline conjugates as potential cytotoxic and DNA topoisomerase I inhibitors

Synthesis of DNA interactive C3-trans-cinnamide linked β-carboline conjugates as potential cytotoxic and DNA topoisomerase I inhibitors

  • Bioorg Med Chem. 2018 Sep 15;26(17):4916-4929. doi: 10.1016/j.bmc.2018.08.031.
Manda Sathish 1,  Sabanis Chetan Dushantrao 2,  Shalini Nekkanti 2,  Ramya Tokala 2,  Soujanya Thatikonda 3,  Yellaiah Tangella 1,  Gunda Srinivas 4,  Shirisha Cherukommu 4,  Namballa Hari Krishna 2,  Nagula Shankaraiah 5,  Narayana Nagesh 6,  Ahmed Kamal 7
Affiliations

Affiliations

  • 1 Medicinal Chemistry & Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 2 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 4 CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.
  • 5 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
  • 6 CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India. Electronic address: nagesh@ccmb.res.in.
  • 7 Medicinal Chemistry & Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi 110 062, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 30172625 DOI: 10.1016/j.bmc.2018.08.031
Abstract

A series of new C3-trans-cinnamide linked β-carboline conjugates has been synthesized by coupling between various β-carboline amines and substituted cinnamic acids. Evaluation of their anti-proliferative activity against a panel of selected human Cancer cell lines such as A549 (lung Cancer), MCF-7 (breast Cancer), B16 (melanoma), HeLa (cervical Cancer) and a normal cell line NIH3T3 (mouse embryonic fibroblast cell line), suggested that the newly designed conjugates are considerably active against all the tested Cancer cell lines with IC50 values 13-45 nM. Moreover, the conjugates 8v and 8x were the most active against MCF-7 cells (14.05 nM and 13.84 nM respectively) and also even potent on Other cell lines tested. Further, detailed investigations such as cell cycle analysis, Apoptosis induction study, Topoisomerase I inhibition assay, DNA binding affinity and docking studies revealed that these new conjugates are DNA interactive Topoisomerase I inhibitors.

Keywords

Anticancer activity; DNA intercalation; Topoisomerase I; Trans-cinnamides; β-Carbolines.

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