{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:56:06Z","timestamp":1787010966545,"version":"build-2736575974"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In this study we utilized the concept of rational drug design to identify novel compounds with optimal selectivity, efficacy and safety, which would bind to the target enzyme pteridine reductase 1 (PTR1) in\n            <jats:italic>Leishmania<\/jats:italic>\n            parasites. Twelve compounds afforded from Baylis-Hillman chemistry were docked by using the QUANTUM program into the active site of\n            <jats:italic>Leishmania donovani<\/jats:italic>\n            PTR1 homology model. The biological activity for these compounds was estimated in green fluorescent protein-transfected\n            <jats:italic>L. donovani<\/jats:italic>\n            promastigotes, and the most potential analogue was further investigated in intracellular amastigotes. Structure-activity relationship based on homology model drawn on our recombinant enzyme was substantiated by recombinant enzyme inhibition assay and growth of the cell culture. Flow cytometry results indicated that 7-(4-chlorobenzyl)-3-methyl-4-(4-trifluoromethyl-phenyl)-3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-one (compound 7) was 10 times more active on\n            <jats:italic>L. donovani<\/jats:italic>\n            amastigotes (50% inhibitory concentration [IC\n            <jats:sub>50<\/jats:sub>\n            ] = 3 \u03bcM) than on promastigotes (IC\n            <jats:sub>50<\/jats:sub>\n            = 29 \u03bcM). Compound 7 exhibited a\n            <jats:italic>\n              K\n              <jats:sub>i<\/jats:sub>\n            <\/jats:italic>\n            value of 0.72 \u03bcM in a recombinant enzyme inhibition assay. We discovered that novel pyrimido[1,2-a]pyrimidin-2-one systems generated from the allyl amines afforded from the Baylis-Hillman acetates could have potential as a valuable pharmacological tool against the neglected disease visceral leishmaniasis.\n          <\/jats:p>","DOI":"10.1128\/aac.00436-10","type":"journal-article","created":{"date-parts":[[2010,11,30]],"date-time":"2010-11-30T09:45:25Z","timestamp":1291110325000},"page":"659-666","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["<i>In Silico<\/i>\n            Screening, Structure-Activity Relationship, and Biologic Evaluation of Selective Pteridine Reductase Inhibitors Targeting Visceral Leishmaniasis"],"prefix":"10.1128","volume":"55","author":[{"given":"Jaspreet","family":"Kaur","sequence":"first","affiliation":[{"name":"Drug Target Discovery and Development Division, Central Drug Research Institute, Chattar Manzil Palace, CSIR, P.O. Box No. 173, Lucknow 226001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Kumar","sequence":"additional","affiliation":[{"name":"Drug Target Discovery and Development Division, Central Drug Research Institute, Chattar Manzil Palace, CSIR, P.O. Box No. 173, Lucknow 226001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sargam","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Connexious Life Sciences, Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Pathak","sequence":"additional","affiliation":[{"name":"Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattar Manzil Palace, CSIR, P.O. Box No. 173, Lucknow 226001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Batra","sequence":"additional","affiliation":[{"name":"Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattar Manzil Palace, CSIR, P.O. Box No. 173, Lucknow 226001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Dayanand Anglo-Vedic (PG) College, Dehradun 248001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeloo","family":"Singh","sequence":"additional","affiliation":[{"name":"Drug Target Discovery and Development Division, Central Drug Research Institute, Chattar Manzil Palace, CSIR, P.O. 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