학술논문
Synthesis of DNA interactive C3-trans-cinnamide linked β-carboline conjugates as potential cytotoxic and DNA topoisomerase I inhibitors.
Document Type
Academic Journal
Author
Sathish M; Medicinal Chemistry & Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.; Chetan Dushantrao S; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.; Nekkanti S; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.; Tokala R; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.; Thatikonda S; Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.; Tangella Y; Medicinal Chemistry & Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.; Srinivas G; CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.; Cherukommu S; CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.; Hari Krishna N; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.; Shankaraiah N; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.; Nagesh N; CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India. Electronic address: nagesh@ccmb.res.in.; Kamal A; 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.
Source
Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE
Subject
Language
English
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 IC 50 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.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
(Copyright © 2018 Elsevier Ltd. All rights reserved.)