{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:28:42Z","timestamp":1785943722202,"version":"3.56.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["DST\/INT\/Brazil\/RPO-01\/2009\/2"],"award-info":[{"award-number":["DST\/INT\/Brazil\/RPO-01\/2009\/2"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["CSC-0108"],"award-info":[{"award-number":["CSC-0108"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/PR4456\/MED\/29\/355\/2012"],"award-info":[{"award-number":["BT\/PR4456\/MED\/29\/355\/2012"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Visceral leishmaniasis is a fatal parasitic disease, and there is an emergent need for development of effective drugs against this neglected tropical disease. We report here the development of a novel spirooxindole derivative,\n            <jats:italic>N<\/jats:italic>\n            -benzyl-2,2\u2032\u03b1-3,3\u2032,5\u2032,6\u2032,7\u2032,7\u03b1,\u03b1\u2032-octahydro-2methoxycarbonyl-spiro[indole-3,3\u2032-pyrrolizidine]-2-one (compound 4c), which inhibits\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>\n            topoisomerase IB (LdTopIB) and kills the wild type as well as drug-resistant parasite strains. This compound inhibits catalytic activity of LdTopIB in a competitive manner. Unlike camptothecin (CPT), the compound does not stabilize the DNA-topoisomerase IB cleavage complex; rather, it hinders drug-DNA-enzyme covalent complex formation. Fluorescence studies show that the stoichiometry of this compound binding to LdTopIB is 2:1 (mole\/mole), with a dissociation constant of 6.65 \u03bcM. Molecular docking with LdTopIB using the stereoisomers of compound 4c produced two probable hits for the binding site, one in the small subunit and the other in the hinge region of the large subunit of LdTopIB. This spirooxindole is highly cytotoxic to promastigotes of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. donovani<\/jats:named-content>\n            and also induces apoptosis-like cell death in the parasite. Treatment with compound 4c causes depolarization of mitochondrial membrane potential, formation of reactive oxygen species inside parasites, and ultimately fragmentation of nuclear DNA. Compound 4c also effectively clears amastigote forms of wild-type and drug-resistant parasites from infected mouse peritoneal macrophages but has less of an effect on host macrophages. Moreover, compound 4c showed strong antileishmanial efficacies in the BALB\/c mouse model of leishmaniasis. This compound potentially can be used as a lead for developing excellent antileishmanial agents against emerging drug-resistant strains of the parasite.\n          <\/jats:p>","DOI":"10.1128\/aac.00352-16","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T02:53:53Z","timestamp":1470711233000},"page":"6281-6293","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":60,"title":["A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both\n            <i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            by Targeting Type IB Topoisomerase"],"prefix":"10.1128","volume":"60","author":[{"given":"Sourav","family":"Saha","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiranjit","family":"Acharya","sequence":"additional","affiliation":[{"name":"Laboratory of Catalysis and Chemical Biology, Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uttam","family":"Pal","sequence":"additional","affiliation":[{"name":"Structural Biology &amp; Bio-Informatics Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somenath Roy","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahini","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakul C.","family":"Maiti","sequence":"additional","affiliation":[{"name":"Structural Biology &amp; Bio-Informatics Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parasuraman","family":"Jaisankar","sequence":"additional","affiliation":[{"name":"Laboratory of Catalysis and Chemical Biology, Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemanta K.","family":"Majumder","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.65.070196.003223"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm831"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2010.04.012"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(03)00058-5"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1748"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.05.008"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2010.10-0171"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2011.10-0661"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46841-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.06.005"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203991200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1330762100"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.03.078"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.9.3726"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.6.994"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20071286"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj502"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201316"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.10.004"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402104"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.072785"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja412350f"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi1009419"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb300648v"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2763"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201104071"},{"key":"e_1_3_3_28_2","first-page":"277","article-title":"Synthesis of heterocyclic compounds based on isatin through 1,3-dipolar cycloaddition reactions","volume":"1","author":"Lashgari N","year":"2012","unstructured":"Lashgari N, Ziarani GM. 2012. Synthesis of heterocyclic compounds based on isatin through 1,3-dipolar cycloaddition reactions. Arch Org Chem 1:277\u2013320.","journal-title":"Arch Org Chem"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200800106"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo0004658"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.04.023"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20000717)39:14<2540::AID-ANIE2540>3.0.CO;2-R"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja051147z"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.12.037"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193225"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.12.039"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44700-4"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401435"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(82)87029-8"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(85)17024-2"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21256"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-4-17"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki481"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn186"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr366"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.7160"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02193-13"},{"key":"e_1_3_3_49_2","first-page":"80","article-title":"Resistance to the Khartoum strain of Leishmania donovani","volume":"45","author":"Stauber AL","year":"1956","unstructured":"Stauber AL. 1956. Resistance to the Khartoum strain of Leishmania donovani. Rice Inst Pam 45:80\u201396.","journal-title":"Rice Inst Pam"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200701342"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200300050"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2012.02.097"},{"key":"e_1_3_3_53_2","volume-title":"1,3-Dipolar cycloaddition chemistry, vol 1 and 2","author":"Padwa A","year":"1984","unstructured":"Padwa A (ed). 1984. 1,3-Dipolar cycloaddition chemistry, vol 1 and 2. Wiley, New York, NY."},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1995-4882"},{"key":"e_1_3_3_55_2","first-page":"6433","article-title":"X=Y-ZH compounds as potential 1,3-dipoles. 28. The iminium ion route to azomethine ylides","volume":"46","author":"Ardill H","year":"1990","unstructured":"Ardill H, Dorrity MJR, Grigg R, Leon-Ling MS, Malone JF, Sridharan V, Thianpatanagul S. 1990. X=Y-ZH compounds as potential 1,3-dipoles. 28. The iminium ion route to azomethine ylides. Background and reaction of amines with bifunctional ketones Tetrahedron 46:6433\u20136448.","journal-title":"Background and reaction of amines with bifunctional ketones Tetrahedron"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2007.07.085"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5356.1534"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03395"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412417200"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010991200"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2003.12.007"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm669"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1977"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1615"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41552-9"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603678200"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2010.06.003"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1912"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00352-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00352-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T23:08:39Z","timestamp":1645484919000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00352-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":67,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1128\/AAC.00352-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.00352-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2016-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}