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.
- 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: [email protected].
- 4. Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, India. Electronic address: [email protected].
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.