{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:19:44Z","timestamp":1762521584697},"reference-count":19,"publisher":"Cambridge University Press (CUP)","issue":"8","license":[{"start":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T00:00:00Z","timestamp":1364947200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>In view of the mandate from the World Health Organization (WHO) for developing novel drug candidates against human lymphatic filariasis, dihydrofolate reductase (DHFR) inhibitors are explored as potential antifilarial agents. The <jats:italic>in vitro<\/jats:italic> biological evaluation of an in-house library of 12 diverse antifolate compounds with 2,4-diaminopyrimidine and 2,4-diamino-<jats:italic>s<\/jats:italic>-triazine structural features against <jats:italic>Brugia malayi<\/jats:italic> is reported. To confirm the DHFR inhibitory potential of these compounds, reversal studies using folic acid and folinic acid were undertaken. Inhibition of DHFR can induce apoptosis; in this light, preliminary evidence of apoptosis by test compounds was detected using ethidium bromide\u2013acridine orange staining and the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition assay. Among the evaluated compounds, 3 showed significant activity against both microfilariae and adult worms. The effects of 2 of these compounds were mostly reversed by folic acid, validating DHFR inhibitory activity. Partial reversal of the effect of 2 compounds by folinic acid and non-reversal of the effect of the third compound both by folic and folinic acids are discussed. This study opens new avenues for the discovery of lead molecules by exploiting the folate pathway against one of the major neglected tropical diseases, filariasis.<\/jats:p>","DOI":"10.1017\/s0031182013000309","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T17:22:51Z","timestamp":1365009771000},"page":"959-965","source":"Crossref","is-referenced-by-count":22,"title":["Exploration of 2, 4-diaminopyrimidine and 2, 4-diamino-s-triazine derivatives as potential antifilarial agents"],"prefix":"10.1017","volume":"140","author":[{"given":"R. D.","family":"SHARMA","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"BAG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. 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R.","family":"REDDY","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2013,4,3]]},"reference":[{"key":"S0031182013000309_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2009.09.004"},{"key":"S0031182013000309_ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-006-0045-4"},{"key":"S0031182013000309_ref1","doi-asserted-by":"publisher","DOI":"10.2307\/3277515"},{"key":"S0031182013000309_ref3","doi-asserted-by":"publisher","DOI":"10.3109\/14756360903179443"},{"key":"S0031182013000309_ref16","first-page":"277","article-title":"Filarial infections of Mastomys natalensis and their relevance for experimental chemotherapy","volume":"38","author":"Sanger","year":"1981","journal-title":"Acta Tropica"},{"key":"S0031182013000309_ref10","first-page":"171","article-title":"PARP cleavage as a means of assessing apoptosis","volume":"88","author":"Mullen","year":"2004","journal-title":"Methods in Molecular Medicine"},{"key":"S0031182013000309_ref11","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3469"},{"key":"S0031182013000309_ref13","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-5-12"},{"key":"S0031182013000309_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.03.031"},{"key":"S0031182013000309_ref7","doi-asserted-by":"publisher","DOI":"10.2174\/138161207780162827"},{"key":"S0031182013000309_ref8","first-page":"1","article-title":"Biochemical targets in filarial worms for selective antifilarial drug design","volume":"50","author":"Gupta","year":"2005","journal-title":"Acta Parasitologica"},{"key":"S0031182013000309_ref9","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/129.1.25"},{"key":"S0031182013000309_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(97)90405-3"},{"key":"S0031182013000309_ref14","first-page":"467","article-title":"In vitro effect of four herbal plants on the motility of Brugia malayi microfilariae","volume":"127","author":"Sahare","year":"2008","journal-title":"Indian Journal of Medical Research"},{"key":"S0031182013000309_ref15","first-page":"128","article-title":"Anti-microfilarial activity of methanolic extract of Vitex negundo and Aegle marmelos and their phytochemical analysis","volume":"46","author":"Sahare","year":"2008","journal-title":"Indian Journal of Experimental Biology"},{"key":"S0031182013000309_ref17","article-title":"Direct microscopy: an alternative tool for assessment of viability of microfilariae","volume":"3","author":"Sharma","year":"2008","journal-title":"Internet Journal of Parasitic Diseases"},{"key":"S0031182013000309_ref18","first-page":"1023","article-title":"Novel microfilaricidal activity of nanosilver","volume":"7","author":"Singh","year":"2012","journal-title":"International Journal of Nanomedicine"},{"key":"S0031182013000309_ref19","unstructured":"World Health Organization (2012). http:\/\/www.who.int\/mediacentre\/factsheets\/fs102\/en\/."},{"key":"S0031182013000309_ref6","first-page":"497","article-title":"Isolation of microfilariae from blood on iso-osmotic percoll gradients","volume":"79","author":"Chandrashekar","year":"1984","journal-title":"Indian Journal of Medical Research"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0031182013000309","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T20:58:41Z","timestamp":1556053121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0031182013000309\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,3]]},"references-count":19,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["S0031182013000309"],"URL":"https:\/\/doi.org\/10.1017\/s0031182013000309","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,3]]}}}