{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:40:06Z","timestamp":1793497206026,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1016\/j.ejmech.2023.115524","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T08:57:49Z","timestamp":1685609869000},"page":"115524","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Discovery, SAR and mechanistic studies of quinazolinone-based acetamide derivatives in experimental visceral leishmaniasis"],"prefix":"10.1016","volume":"257","author":[{"given":"Alisha","family":"Ansari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Seth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukul","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tooba","family":"Qamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarita","family":"Katiyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind K.","family":"Jaiswal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Rani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetapadma","family":"Majhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabi S.","family":"Bhatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajdeep","family":"Guha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyan","family":"Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koneni V.","family":"Sashidhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9907-539X","authenticated-orcid":false,"given":"Susanta","family":"Kar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2023.115524_bib1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","volume":"392","author":"Burza","year":"2018","journal-title":"Leishmaniasis, Lancet"},{"key":"10.1016\/j.ejmech.2023.115524_bib2","series-title":"WHO. Leishmaniasis","year":"2020"},{"key":"10.1016\/j.ejmech.2023.115524_bib3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1017\/S0031182016002523","article-title":"Chemotherapy of leishmaniasis: present challenges","volume":"145","author":"Uliana","year":"2018","journal-title":"Parasitology"},{"key":"10.1016\/j.ejmech.2023.115524_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002914","article-title":"Immune regulation during chronic visceral leishmaniasis","volume":"8","author":"Faleiro","year":"2014","journal-title":"PLoS Neglected Trop. Dis."},{"key":"10.1016\/j.ejmech.2023.115524_bib5","doi-asserted-by":"crossref","first-page":"670","DOI":"10.3389\/fimmu.2019.00670","article-title":"Cytokines: key determinants of resistance or disease progression in visceral leishmaniasis: opportunities for novel diagnostics and immunotherapy","volume":"10","author":"Dayakar","year":"2019","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejmech.2023.115524_bib6","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1093\/jac\/dkw448","article-title":"Pharmacological inhibition of p110\u03b4 subunit of PI3K confers protection against experimental leishmaniasis","volume":"72","author":"Khadem","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.ejmech.2023.115524_bib7","doi-asserted-by":"crossref","first-page":"8951","DOI":"10.1021\/acs.jmedchem.1c00004","article-title":"Discovery, optimization, and evaluation of quinazolinone derivatives with novel linkers as orally efficacious phosphoinositide-3-kinase delta inhibitors for treatment of inflammatory diseases","volume":"64","author":"Liu","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115524_bib8","unstructured":"K. Hoegenauer, N. Soldermann, F. Stauffer, P. Furet, N. Graveleau, A.B. Smith, C. Hebach, G.J. Hollingworth, I. Lewis, S. Gutmann, G. Rummel, M. Knapp, R.M. Wolf, J. Blanz, R. Feifel, C. Burkhart, F. Z\u00e9cri, Discovery and Pharmacological Characterization of Novel Quinazoline-Based PI3K Delta-Selective Inhibitors."},{"key":"10.1016\/j.ejmech.2023.115524_bib9","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.4049\/jimmunol.0903177","article-title":"The p110 delta isoform of phosphatidylinositol 3-kinase controls the quality of secondary anti-Leishmania immunity by regulating expansion and effector function of memory T cell subsets","volume":"184","author":"Liu","year":"2010","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejmech.2023.115524_bib10","doi-asserted-by":"crossref","first-page":"9787","DOI":"10.1016\/j.tet.2006.07.098","article-title":"The chemistry of recently isolated naturally occurring quinazolinone alkaloids","volume":"62","author":"Mhaske","year":"2006","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2023.115524_bib11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/07391102.2015.1135298","article-title":"Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation","volume":"35","author":"Pandey","year":"2017","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.ejmech.2023.115524_bib12","doi-asserted-by":"crossref","first-page":"8900","DOI":"10.1073\/pnas.1913788117","article-title":"Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells","volume":"117","author":"Kim","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2023.115524_bib13","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1080\/21655979.2016.1149270","article-title":"The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment","volume":"7","author":"Saint-L\u00e9ger","year":"2016","journal-title":"Bioengineered"},{"key":"10.1016\/j.ejmech.2023.115524_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.molbiopara.2022.111510","article-title":"Aminoacyl-tRNA synthetase (AARS) as an attractive drug target in neglected tropical trypanosomatid diseases-Leishmaniasis, Human African Trypanosomiasis and Chagas disease","volume":"251","author":"Kushwaha","year":"2022","journal-title":"Mol. Biochem. Parasitol."},{"key":"10.1016\/j.ejmech.2023.115524_bib15","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa3575","article-title":"The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs","volume":"7","author":"Herman","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejmech.2023.115524_bib16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nchembio.790","article-title":"Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase","volume":"8","author":"Keller","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2023.115524_bib17","first-page":"1495","article-title":"Targeting prolyl-tRNA synthetase to accelerate drug discovery against malaria","volume":"25","author":"Jain","year":"2017","journal-title":"Leishmaniasis, Toxoplasmosis, Cryptosporidiosis, and Coccidiosis, Structure"},{"key":"10.1016\/j.ejmech.2023.115524_bib18","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1021\/acsmedchemlett.1c00589","article-title":"Indole-containing pyrazino[2,1-b]quinazoline-3,6-diones active against Plasmodium and trypanosomatids","volume":"13","author":"Long","year":"2022","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2023.115524_bib19","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1021\/jm400053v","article-title":"Discovery of a new class of natural product-inspired quinazolinone hybrid as potent anti-leishmanial agents","volume":"56","author":"Sharma","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115524_bib20","doi-asserted-by":"crossref","first-page":"12290","DOI":"10.1021\/acs.jmedchem.0c00530","article-title":"Amide bond bioisosteres: strategies, synthesis, and successes","volume":"63","author":"Kumari","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115524_bib21","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1021\/jm5015742","article-title":"Novel 3-nitrotriazole-based amides and carbinols as bifunctional antichagasic agents","volume":"58","author":"Papadopoulou","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115524_bib22","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1021\/ml3001825","article-title":"Neuroprotective tri- and tetracyclic BChE inhibitors releasing reversible inhibitors upon carbamate transfer","volume":"3","author":"Darras","year":"2012","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2023.115524_bib23","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1055\/s-0033-1339466","article-title":"One-pot regioselective synthesis of imidazole and 2,3-dihydroquinazolinone derivatives \u2013 an easy access to \u2018nature-like molecules\u2019; Part XIII in the series: \u2018studies on novel synthetic methodologies\u2019","volume":"24","author":"Sashidhara","year":"2013","journal-title":"Synlett"},{"key":"10.1016\/j.ejmech.2023.115524_bib24","doi-asserted-by":"crossref","first-page":"62194","DOI":"10.1039\/C5RA11262A","article-title":"Metal-free one-pot synthesis of 1,3-diazaheterocyclic compounds via I2-mediated oxidative C\u2013N bond formation","volume":"5","author":"Tian","year":"2015","journal-title":"RSC Adv."},{"key":"10.1016\/j.ejmech.2023.115524_bib25","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.ejmech.2011.02.033","article-title":"Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease","volume":"46","author":"Ma","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115524_bib26","doi-asserted-by":"crossref","unstructured":"D.L. Sacks, P.C. Melby, Animal models for the analysis of immune responses to leishmaniasis (Chapter 19) Curr. Protoc. Im. (2001) Unit 19.2.doi: 10.1002\/0471142735.im1902s28.","DOI":"10.1002\/0471142735.im1902s28"},{"key":"10.1016\/j.ejmech.2023.115524_bib27","unstructured":"W. Nawrocka, M. Zimecki, Syntheses of Novel 3-Amino-2(1h)-Thioxo-4(3h)-Quinazolinones and Evaluation of Their Immunotropic Activity. Part III."},{"key":"10.1016\/j.ejmech.2023.115524_bib28","unstructured":"M. Sharma, R. Chauhan K Fau - Shivahare, P. Shivahare R Fau - Vishwakarma, M.K. Vishwakarma P Fau - Suthar, A. Suthar Mk Fau - Sharma, S. Sharma A Fau - Gupta, J.K. Gupta S Fau - Saxena, J. Saxena Jk Fau - Lal, P. Lal J Fau - Chandra, B. Chandra P Fau - Kumar, P.M.S. Kumar B Fau - Chauhan, P.M. Chauhan, Discovery of a New Class of Natural Product-Inspired Quinazolinone Hybrid as Potent Anti-leishmanial Agents."},{"key":"10.1016\/j.ejmech.2023.115524_bib29","doi-asserted-by":"crossref","first-page":"367","DOI":"10.4049\/jimmunol.1100076","article-title":"Myeloid cell IL-10 production in response to leishmania involves inactivation of glycogen synthase kinase-3\u03b2 downstream of phosphatidylinositol-3 kinase","volume":"188","author":"Nandan","year":"2012","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejmech.2023.115524_bib30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.exppara.2008.12.010","article-title":"Activation of PI3K\/Akt signaling has a dominant negative effect on IL-12 production by macrophages infected with Leishmania amazonensis promastigotes","volume":"122","author":"Ruhland","year":"2009","journal-title":"Exp. Parasitol."},{"key":"10.1016\/j.ejmech.2023.115524_bib31","unstructured":"M.A. Hermida, J. Dinesh Kumar, N.R. Leslie, GSK3 and its Interactions with the PI3K\/AKT\/mTOR Signalling Network."},{"key":"10.1016\/j.ejmech.2023.115524_bib32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0156032","article-title":"A GCN2-like eIF2\u03b1 kinase (LdeK1) of leishmania donovani and its possible role in stress response","volume":"11","author":"Rao","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2023.115524_bib33","article-title":"Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis","author":"de Macedo-Silva","year":"2011","journal-title":"Mol Biol Int"},{"key":"10.1016\/j.ejmech.2023.115524_bib34","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/s41419-019-2038-7","article-title":"Leishmania donovani parasite requires Atg8 protein for infectivity and survival under stress","volume":"10","author":"Giri","year":"2019","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2023.115524_bib35","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1073\/pnas.0712145105","article-title":"A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy","volume":"105","author":"Lee","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2023.115524_bib36","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/sj.cdd.4401435","article-title":"Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani","volume":"11","author":"Sen","year":"2004","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.ejmech.2023.115524_bib37","doi-asserted-by":"crossref","first-page":"E575","DOI":"10.1073\/pnas.1213839110","article-title":"Antimony-resistant but not antimony-sensitive Leishmania donovani up-regulates host IL-10 to overexpress multidrug-resistant protein 1","volume":"110","author":"Mukherjee","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2023.115524_bib38","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/0002-9343(87)90948-X","article-title":"Visceral leishmaniasis in immunocompromised hosts","volume":"83","author":"Fern\u00e1ndez-Guerrero","year":"1987","journal-title":"Am. J. Med."},{"key":"10.1016\/j.ejmech.2023.115524_bib39","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1021\/acs.jmedchem.6b01447","article-title":"Anti-leishmanial activity of pyrazolopyridine derivatives and their potential as an adjunct therapy with miltefosine","volume":"60","author":"Anand","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115524_bib40","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0001-706X(93)90083-N","article-title":"A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites","volume":"55","author":"Huber","year":"1993","journal-title":"Acta Trop."},{"key":"10.1016\/j.ejmech.2023.115524_bib41","first-page":"1506","article-title":"Synthesis and in-vivo pharmacological evaluation of some novel 4 (3H)-quinazolinone derivatives as potential anti-malarial agents","volume":"4","author":"Bule","year":"2015","journal-title":"Int. J. Res. Dev. Pharm. Life Sci."},{"key":"10.1016\/j.ejmech.2023.115524_bib42","doi-asserted-by":"crossref","unstructured":"Y.S. Birhan, A.A. Bekhit, A. Hymete, In Vivo Antimalarial Evaluation of Some 2,3-Disubstituted-4(3h)-Quinazolinone Derivatives.","DOI":"10.1186\/s13588-014-0010-1"},{"key":"10.1016\/j.ejmech.2023.115524_bib43","doi-asserted-by":"crossref","first-page":"5655","DOI":"10.1021\/acs.jmedchem.9b00628","article-title":"Synthesis, biological evaluation, structure-activity relationship, and mechanism of action studies of quinoline-metronidazole derivatives against experimental visceral leishmaniasis","volume":"62","author":"Upadhyay","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115524_bib44","doi-asserted-by":"crossref","first-page":"5916","DOI":"10.1128\/AAC.02459-14","article-title":"Induction of mitochondrial dysfunction and oxidative stress in Leishmania donovani by orally active clerodane diterpene","volume":"58","author":"Kathuria","year":"2014","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423004907?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423004907?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T14:53:06Z","timestamp":1730991186000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423004907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":44,"alternative-id":["S0223523423004907"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115524","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery, SAR and mechanistic studies of quinazolinone-based acetamide derivatives in experimental visceral leishmaniasis","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115524","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115524"}}