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

Bioorganic & Medicinal Chemistry
Manda SathishAhmed Kamal

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.

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Citations

Mar 12, 2020·Organic & Biomolecular Chemistry·Darshana BoraNagula Shankaraiah
Aug 17, 2019·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Nagula ShankaraiahRamya Tokala
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Jun 15, 2021·RSC Medicinal Chemistry·Jay Prakash SoniNagula Shankaraiah
Aug 1, 2021·European Journal of Medicinal Chemistry·Bo Luo, Xinqiang Song

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