Biopolyphenolics as antioxidants: Studies under an Indo-Italian CSIR-CNR project

Materials and methods:We synthesized 27 coumarin derivatives (mostly having 4-methyl moiety) and examined their cytotoxic effect on three human cancer cell lines, K562 (chronic myelogenous leukemia), LS180 (colon adenocarcinoma), and MCF-7 (breast adenocarcinoma) by MTT reduction assay. Screened compounds included 7-hydroxy-4-methylcoumarins (7-HMCs), 7-acetoxy-4-methylcoumarins (7-AMCs), and different dihydroxy-4-methylcoumarin (DHMC) and diacetoxy-4-methylcoumarin (DAMC) derivatives. Some compounds with methoxy, amine, and bromine substitutions were also examined.Results: 7,8-DHMCs bearing alkyl groups at C3 position were the most effective subgroup, and of which, the most potent is compound 11, with an n-decyl chain at C3, which had IC 50 values of 42.4, 25.2, and 25.1 mM against K562, LS180, and MCF-7 cells, respectively. The second most active subgroup was 7,8-DAMCs containing ethoxycarbonylmethyl and ethoxycarbonylethyl moieties at C3 position. Compound 27 (6-bromo-4-bromomethyl-7-hydroxycoumarin), the only derivative containing bromine also showed reasonable cytotoxic activities (IC 50 range: 32.7-45.8 mM). Discussion and conclusion: This structure-activity relationship (SAR) study of 4-methylcoumarins shows that further investigation of these derivatives may lead to the discovery of novel anticancer agents.

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“…This can probably be explained by the strong effect that can be brought about by the presence of the catechol moiety (Foti et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Structure–activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Miri

Nejati

Saso

et al. 2015

Pharmaceutical Biology

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“…Few authors gave proposed mechanisms of action (Foti et al, 2005) and theoretical elucidation of structure-activity relationships (Zhang & Wang, 2004) for coumarins to scavenge radicals. This issue will be subjected to our further research.…”

Section: Comparison Of Two Testing Methodsmentioning

confidence: 99%

Synthesis and antioxidant activity of selected 4-methylcoumarins

2009

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“…Specific proteins were detected using monoclonal antibodies against E-cadherin, N-cadherin, p-120 catenin, vimentin and α-tubulin, and total proteins were stained using Amido Black. Blots are representatives from at least two independent experiments disease due to their therapeutic and preventive capacities [40]. Both compounds 3 and 5 demonstrated antioxidative properties, although compound 3 less so than compound 5.…”

Section: Gene Ontologymentioning

confidence: 99%

Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells

et al. 2010

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Six recently synthesized cyano-substituted heteroaryles, which do not bind to DNA but are highly cytotoxic against the human tumor cell line HeLa, were analyzed for their antitumor mechanisms of action (MOA). They did not interfere with the expression of human papillomavirus oncogenes integrated in the HeLa cell genome, but they did induce strong G1 arrest and result in the activation of caspase-3 and apoptosis. A computational analysis was performed that compared the antiproliferative activities of our compounds in 13 different tumor cell lines with those of compounds listed in the National Cancer Institute database. The results indicate that interference with cytoskeletal function and inhibition of mitosis are the likely antitumor MOA. Furthermore, a second in silico investigation revealed that the tumor cells that are sensitive to the cyano-substituted compounds show differences in their expression of locomotion genes compared with that of insensitive cell lines, thus corroborating the involvement of the cytoskeleton. This MOA was also confirmed experimentally: the cyano-substituted heteroaryles disrupted the actin and the tubulin networks in HeLa cells and inhibited cellular migration. However, further analysis indicated that multiple MOA may exist that depend on the position of the cyano-group; while cyano-substituted naphthiophene reduced the expression of cytoskeletal proteins, cyano-substituted thieno-thiophene-carboxanilide inhibited the formation of cellular reactive oxygen species.

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Biopolyphenolics as antioxidants: Studies under an Indo-Italian CSIR-CNR project

Cited by 16 publications

References 30 publications

Structure–activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Structure–activity relationship studies of 4-methylcoumarin derivatives as anticancer agents

Synthesis and antioxidant activity of selected 4-methylcoumarins

Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells

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