title: Polyoxometalates as potent and selective inhibitors of alkaline phosphatases with profound anticancer and amoebicidal activities.
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, Na(10)[H(2)W(12)O(42)]·27H(2)O (A6) was found to be the most potent inhibitor (K(i) value 313 ± 7 nM), while for tissue non-specific alkaline phosphatase Na(33)[H(7)P(8)W(48)O(184)]·92H(2)O (A3) showed the highest inhibition potency (K(i) 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.
authors.affiliation: Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad, Postal Code 22060, Pakistan. rabiakhan_star@yahoo.com
authors.forename: Rabia
authors.initials: R
authors.lastname: Raza
authors.forename: Abdul
authors.initials: A
authors.lastname: Matin
authors.forename: Sundas
authors.initials: S
authors.lastname: Sarwar
authors.forename: Maria
authors.initials: M
authors.lastname: Barsukova-Stuckart
authors.forename: Masooma
authors.initials: M
authors.lastname: Ibrahim
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kortz
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000562:Amebiasis / Q000188:drug therapy; D000563:Amebicides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology; D008958:Models, Molecular; D017973:Tungsten Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000563:Amebicides; D000970:Antineoplastic Agents; D017973:Tungsten Compounds; D000469:Alkaline Phosphatase