2. Academic Validation
  3. Identification of two novel thiophene analogues as inducers of autophagy mediated cell death in breast cancer cells

Identification of two novel thiophene analogues as inducers of autophagy mediated cell death in breast cancer cells

  • Bioorg Med Chem. 2021 May 1:37:116112. doi: 10.1016/j.bmc.2021.116112.
Chandrima Gain 1,  Aparna Sarkar 2,  Shrea Bural 1,  Moumita Rakshit 2,  Jeet Banerjee 2,  Ankita Dey 2,  Nabendu Biswas 3,  Gandhi K Kar 4,  Abhik Saha 5
Affiliations

Affiliations

  • 1 School of Biotechnology, Presidency University, Second Campus, Plot No. DG/02/02, Premises No. 14-0358, Action Area-ID, New Town, Kolkata 700156, West Bengal, India.
  • 2 Department of Chemistry, Presidency University, 86/1 College Street, Kolkata 700073, West Bengal, India.
  • 3 Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, West Bengal, India.
  • 4 Department of Chemistry, Presidency University, 86/1 College Street, Kolkata 700073, West Bengal, India. Electronic address: gandhi.chem@presiuniv.ac.in.
  • 5 School of Biotechnology, Presidency University, Second Campus, Plot No. DG/02/02, Premises No. 14-0358, Action Area-ID, New Town, Kolkata 700156, West Bengal, India. Electronic address: abhik.dbs@presiuniv.ac.in.
PMID: 33751939 DOI: 10.1016/j.bmc.2021.116112
Abstract

Natural compounds isolated from different medicinal Plants remain one of the major resources of Anticancer drugs due to their enormous chemical diversity. Studies suggested therapeutic potential for various tanshinones, key bioactive lipophilic compounds from the root extracts of Salvia miltiorrhiza Bunge, against multiple cancers including breast carcinoma. We designed, synthesized and evaluated anti-cancer properties of a series of condensed and doubly condensed furophenanthraquinones of tanshinone derivatives on two breast Cancer lines - MCF7 and MDA-MB-231. We identified two thiophene analogues - compounds 48 and 52 with greater anti-proliferative efficiency (~4 fold) as compared to the natural tanshinones. Mechanistically, we showed that both compounds induced Autophagy mediated cell death and partial but significant restoration of cell death in the presence of Autophagy Inhibitor further supported this notion. Both compounds transcriptionally activated several Autophagy genes responsible for autophagosome formation along with two death regulators - GADD34 and CHOP for inducing cell death. Altogether, our studies provide strong evidence to support compounds 48 and 52 as promising leads for further development as Anticancer agents through modulating Autophagy mechanism.

Keywords

Autophagy; Breast cancer; Tanshinones; Thiophene analogues.

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