{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:28:06Z","timestamp":1772774886734,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,8,24]],"date-time":"2014-08-24T00:00:00Z","timestamp":1408838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Government of India","award":["BT\/PR4456\/MED\/29\/355\/2012"],"award-info":[{"award-number":["BT\/PR4456\/MED\/29\/355\/2012"]}]},{"name":"Indo-Brazil project","award":["DST\/INT\/Brazil\/RPO-01\/2009\/2"],"award-info":[{"award-number":["DST\/INT\/Brazil\/RPO-01\/2009\/2"]}]},{"DOI":"10.13039\/501100010892","name":"Department of Science and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010892","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"crossref","award":["CSC 0108"],"award-info":[{"award-number":["CSC 0108"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Leishmania<\/jats:italic>, a protozoan parasite, causes a wide range of human diseases ranging from the localized self\u2010healing cutaneous lesions to fatal visceral leishmaniasis. Toxicity of traditional first line drugs and emergence of drug\u2010resistant strains have worsened the situation. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> topoisomerase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> in kinetoplastid protozoan parasites are of immense interest as drug target because they take part in replication of unusual kinetoplast <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> network. In this study, we have taken target\u2010based therapeutic approaches to combat leishmaniasis. Two isobenzofuranone compounds, viz., (1) 3,5\u2010bis(4\u2010chlorophenyl)\u20107\u2010hydroxyisobenzofuran\u20101(3H)\u2010one (<jats:styled-content style=\"fixed-case\">JVPH<\/jats:styled-content>3) and (2) (4\u2010bromo)\u20103\u2032\u2010hydroxy\u20105\u2032\u2010(4\u2010bromophenyl)\u2010benzophenone(<jats:styled-content style=\"fixed-case\">JVPH<\/jats:styled-content>4) were synthesized chemically and characterized by <jats:styled-content style=\"fixed-case\">NMR<\/jats:styled-content> and mass spectrometry analysis. Activity of type <jats:styled-content style=\"fixed-case\">II DNA<\/jats:styled-content> topoisomerase of leishmania (Ld<jats:styled-content style=\"fixed-case\">TOPII<\/jats:styled-content>) was monitored by decatenation assay and plasmid cleavage assay. The antiparasitic activity of these compounds was checked in experimental <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c mice model of visceral leishmaniasis. Isobenzofuranone derivatives exhibited potent antileishmanial effect on both antimony (Sb) sensitive and resistant parasites. Treatment with isobenzofuranone derivatives on promastigotes caused induction of reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>)\u2010mediated apoptosis like cell death in leishmania. Both the compounds inhibited the decatenation activity of Ld<jats:styled-content style=\"fixed-case\">TOPII<\/jats:styled-content> but have no effect on bi\u2010subunit topoisomerase <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content>. Treatment of Ld<jats:styled-content style=\"fixed-case\">TOPII<\/jats:styled-content> with isobenzofuranone derivatives did not stabilize cleavage complex formation both in vitro and in vivo. Moreover, treatment with isobenzofuranone derivatives on <jats:italic>Leishmania donovani<\/jats:italic>\u2010infected mice resulted in clearance of parasites in liver and spleen by induction of Th1 cytokines. Taken together, our data suggest that these compounds can be exploited as potential antileishmanial agents targeted to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> topoisomerase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> of the parasite.<\/jats:p>","DOI":"10.1002\/prp2.70","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T02:18:06Z","timestamp":1409624286000},"source":"Crossref","is-referenced-by-count":15,"title":["Isobenzofuranone derivatives exhibit antileishmanial effect by inhibiting type <scp>II DNA<\/scp> topoisomerase and inducing host response"],"prefix":"10.1002","volume":"2","author":[{"given":"Amartya","family":"Mishra","sequence":"first","affiliation":[{"name":"Molecular Parasitology Laboratory Indian Institute of Chemical Biology Jadavpur Kolkata 700032 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