2. Academic Validation
  3. Nature-inspired development of unnatural meroterpenoids as the non-toxic anti-colon cancer agents

Nature-inspired development of unnatural meroterpenoids as the non-toxic anti-colon cancer agents

  • Eur J Med Chem. 2018 Dec 5:160:256-265. doi: 10.1016/j.ejmech.2018.08.088.
Md Ashraful Haque 1,  Bethsebie L Sailo 2,  Ganesan Padmavathi 2,  Ajaikumar B Kunnumakkara 3,  Chandan K Jana 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, India.
  • 2 Cancer Biology Laboratory, DBT-AIST International Laboratory for Advanced Biomedicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, India.
  • 3 Cancer Biology Laboratory, DBT-AIST International Laboratory for Advanced Biomedicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, India. Electronic address: kunnumakkara@iitg.ac.in.
  • 4 Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, India. Electronic address: ckjana@iitg.ac.in.
PMID: 30368201 DOI: 10.1016/j.ejmech.2018.08.088
Abstract

Structural analogues of anti-cancer natural product, dysideanone, were synthesized starting from Wieland-Miescher ketone derivative. In vitro studies have been conducted to evaluate the anti-cancer potential of these unnatural meroterpenoids against colon Cancer. Synthesized carbotetracycles were found to be more active as compared to their acyclic carbinol-derivatives. Unnatural carbotetracycles 4b-e, 4h, 4i and 12 were found to be highly effective against the human colon adenocarcinoma cells with IC50 concentrations of 7.5-20 μM. In this series, the carbotetracyclic catechol 4e (IC50 = 7.5 μM) and quinone 12 (IC50 = 8 μM) were found to be the most potent compounds having the IC50 of less than 10 μM with no cytotoxic effect on the normal cells. Downregulation of COX-2 and Survivin and cell cycle arrest eventually leading to Apoptosis were found to be the underlying mechanism of the anti-cancer effect of these unnatural meroterpenoids.

Keywords

Apoptosis; CH arylation; Carbotetracycles; Colon cancer; Meroterpenoids; Natural products.

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