Discovery of 3-(benzofuran-2-ylmethyl)-1H-indole derivatives as potential autophagy inducers in cervical cancer cells.

Autor: Siddiqui SK; Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110002, India., SahayaSheela VJ; Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8501, Japan., Kolluru S; Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110002, India. Electronic address: kollurusrinivas2014@gmail.com., Pandian GN; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8501, Japan., Santhoshkumar TR; Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram 695 014, India., Dan VM; Microbiology Division, Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Palode, Thiruvananthapuram, India. Electronic address: vpindan@jntbgri.res.in., Ramana CV; Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110002, India. Electronic address: vr.chepuri@ncl.res.in.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Oct 01; Vol. 30 (19), pp. 127431. Date of Electronic Publication: 2020 Jul 23.
DOI: 10.1016/j.bmcl.2020.127431
Abstrakt: In this manuscript we have documented the identification of a novel anticancer scaffold 3-(benzofuran-2-ylmethyl)-1H-indole. This scaffold has been designed by tweaking the known bisindolylmethane scaffold of natural products that display a wide range of biological activities. A series of 24 new conjugates have been synthesized and among them 5 derivatives exhibited IC 50 values less than 40 µM against two cervical cancer cell lines SiHa and C33a. Further mechanistic studies of two compounds 3eb and 3ec revealed that the toxicity of these compounds was due to the effective induction of autophagy mediated cell death. The autophagy induction was confirmed by the progressive conversion of LC3I to LC3II and downregulation of p62 in cervical cancer cells.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: