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Issue 47, 2012
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Polyoxometalates as potent and selective inhibitors of alkaline phosphatases with profound anticancer and amoebicidal activities

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Abstract

The biological significance of polyoxometalates is well renowned owing to their anticancer, antiviral and antibiotic properties. Here another therapeutic aspect of polyoxometalates has been explored as alkaline phosphatase inhibitors along with the remarked anticancer and amoebicidal properties. Synthesis and inhibitory studies of a set of seven polyoxotungstates against two major isozymes of alkaline phosphatase i.e. tissue specific and tissue non-specific alkaline phosphatase revealed their promising activity as alkaline phosphatase inhibitors. All compounds exhibited alkaline phosphatase inhibitory potency in nanomolar ranges. For tissue specific alkaline phosphatase, Na10[H2W12O42]·27H2O (A6) was found to be the most potent inhibitor (Ki value 313 ± 7 nM), while for tissue non-specific alkaline phosphatase Na33[H7P8W48O184]·92H2O (A3) showed the highest inhibition potency (Ki values 135 ± 10 nM). Moreover cytotoxicity evaluation of these compounds against lung carcinoma cells and immortalized human corneal epithelial cells demonstrated their anticancer potential with no cytotoxic effects on normal human cell lines. All anticancer drugs result in an impaired immune system and such immunocompromised persons become vulnerable to opportunistic infections specially Acanthamoeba which causes granulomatous amoebic encephalitis (GAE) which almost always results in death. The exclusive property of our tested polyoxotungstates is their strong amoebicidal activity against Acanthamoeba. Hence the study reveals a new window towards cancer therapy with the combined control of elevated levels of alkaline phosphatase and granulomatous amoebic encephalitis in cancer patients.

Graphical abstract: Polyoxometalates as potent and selective inhibitors of alkaline phosphatases with profound anticancer and amoebicidal activities

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Article information


Submitted
04 Aug 2012
Accepted
12 Sep 2012
First published
08 Oct 2012

Dalton Trans., 2012,41, 14329-14336
Article type
Paper

Polyoxometalates as potent and selective inhibitors of alkaline phosphatases with profound anticancer and amoebicidal activities

R. Raza, A. Matin, S. Sarwar, M. Barsukova-Stuckart, M. Ibrahim, U. Kortz and J. Iqbal, Dalton Trans., 2012, 41, 14329
DOI: 10.1039/C2DT31784B

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