2. Academic Validation
  3. A one-pot laccase-catalysed synthesis of coumestan derivatives and their anticancer activity

A one-pot laccase-catalysed synthesis of coumestan derivatives and their anticancer activity

  • Bioorg Med Chem. 2017 Feb 1;25(3):1172-1182. doi: 10.1016/j.bmc.2016.12.025.
Tozama Qwebani-Ogunleye 1,  Natasha I Kolesnikova 1,  Paul Steenkamp 2,  Charles B de Koning 3,  Dean Brady 3,  Kevin W Wellington 4
Affiliations

Affiliations

  • 1 CSIR Biosciences, PO Box 395, Pretoria, South Africa.
  • 2 CSIR Biosciences, PO Box 395, Pretoria, South Africa; Department of Biochemistry, University of Johannesburg, PO Box 524, Auckland Park 2006, South Africa.
  • 3 Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Box, Wits 2050, South Africa.
  • 4 CSIR Biosciences, PO Box 395, Pretoria, South Africa. Electronic address: kwellington@csir.co.za.
PMID: 28041801 DOI: 10.1016/j.bmc.2016.12.025
Abstract

Suberase®, a commercial laccase from Novozymes, was used to catalyse the synthesis of coumestans. The yields, in some cases, were similar to or better than that obtained by Other enzymatic, chemical or electrochemical syntheses. The compounds were screened against renal TK10, melanoma UACC62 and breast MCF7 Cancer cell-lines and the GI50, TGI and LC50 values determined. Anticancer screening showed that the cytostatic effects of the coumestans were most effective against the melanoma UACC62 and breast MCF7 Cancer cell-lines exhibiting potent activities, GI50=5.35 and 7.96μM respectively. Moderate activity was obtained against the renal TK10 Cancer cell-line. The total growth inhibition, based on the TGI values, of several of the compounds was better than that of etoposide against the melanoma UACC62 and the breast MCF7 Cancer cell lines. Several compounds, based on the LC50 values, were also more lethal than etoposide against the same Cancer cell lines. The SAR for the coumestans is similar against the melanoma UACC62 and breast MCF7 cell lines. The compound having potent activity against both breast MCF7 and melanoma UACC62 cell lines has a methyl group on the benzene ring (ring A) as well as on the catechol ring (ring B). Anticancer activity decreases when methoxy and halogen substituents are inserted on rings A and B.

Keywords

Anticancer activity; Biocatalysis; Breast cancer; Coumestans; Laccase; Melanoma cancer; Michael addition; Renal cancer; Wedelolactone analogues.

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