{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:21:03Z","timestamp":1787772063367,"version":"build-2784847793"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>Isatin derivatives have excited attention due to their biological attractions, especially, anticancer properties. Isatin analogs such as semaxanib and sunitinib were exposed to tyrosine kinase inhibitory properties. N-substituted isatins were reported to show cytotoxic activity. On the other, the extension of impressive and cost-effective agents against leishmaniasis is necessary in third-world countries. The capability of isatin derivatives to create novel anticancer and anti-leishmanial compounds has been identified in medicinal chemistry research. The current study aimed to synthesize N-alkyl-isatin-3-imino aromatic amine compounds and evaluate their biological effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>Synthesis started with the formation of 2-chloro-N-phenylacetamide derivatives by the reaction of aniline derivatives with chloroacetyl chloride. N-alkylation of isatin was performed in the presence of K2CO3 in N, N-dimethylformamide. Final products were prepared via the condensation of N-alkyl isatin derivatives with aromatic amines. Cell viability was checked out by using the MTT assay against cancer cells. Final compounds were screened for anti-leishmanial activity. The molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase to define the possible interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings\/Results:<\/jats:title>\n                    <jats:p>\n                      Compounds 5c and 4d with IC\n                      <jats:sub>50<\/jats:sub>\n                      value of 50 \u03bc\u039c showed cytotoxic activity on the MCF-7 cell line. Compound 5b presented anti-leishmanial activity against promastigote form after 48 h (IC\n                      <jats:sub>50<\/jats:sub>\n                      :59 \u03bc\u039c) and 72 h (IC\n                      <jats:sub>50<\/jats:sub>\n                      : 41 \u03bc\u039c) incubations. The highest docking score was -7.33 kcal\/mol for compound 4d.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications:<\/jats:title>\n                    <jats:p>The nature of substitution in the N1 region of isatin seems to be able to influence the cytotoxic activity. Based on the obtained results of docking and cytotoxic tests, compound 4d seems to be a good compound for further investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/rps.rps_244_22","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T12:05:19Z","timestamp":1711973119000},"page":"238-250","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Molecular docking and synthesis of N-alkyl-isatin-3-imino aromatic amine derivatives and their antileishmanial and cytotoxic activities"],"prefix":"10.4103","volume":"19","author":[{"given":"Farshid","family":"Hassanzadeh","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Hossein","family":"Hejazi","sequence":"additional","affiliation":[{"name":"Skin Disease and Leishmaniasis Research Center, Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Jafari","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran"},{"name":"Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh Mohammadi","family":"fard","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojjat","family":"Sadeghi-aliabadi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"R1-20240909","doi-asserted-by":"crossref","first-page":"23","DOI":"10.25259\/CMAS_03_04_2021","article-title":"Screening technologies for cervical cancer: overview","volume":"19","author":"Banerjee","year":"2022","journal-title":"Cytojournal"},{"issue":"1","key":"R2-20240909","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/2211738507666190122111224","article-title":"Drug combinations in breast cancer therapy","volume":"7","author":"Fisusi","year":"2019","journal-title":"Pharm Nanotechnol"},{"issue":"10","key":"R3-20240909","doi-asserted-by":"crossref","first-page":"e10204","DOI":"10.1590\/1414-431x202010204","article-title":"Anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide in mice","volume":"53","author":"Dantas","year":"2020","journal-title":"Braz J Med Biol Res"},{"issue":"4","key":"R4-20240909","doi-asserted-by":"crossref","first-page":"248","DOI":"10.56808\/3027-7922.2498","article-title":"Synthesis and anti-inflammatory effects evaluation of 1, 3 substituted isatin derivatives","volume":"45","author":"Hassanzadeh","year":"2021","journal-title":"Thai J Pharm Sci"},{"issue":"3","key":"R5-20240909","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.ejmech.2009.12.010","article-title":"QSAR study of isatin analogues as in vitro anti-cancer agents","volume":"45","author":"Sabet","year":"2010","journal-title":"Eur J Med Chem"},{"issue":"6","key":"R6-20240909","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1016\/j.bmc.2007.12.026","article-title":"N-phenethyl and N-naphthylmethyl isatins and analogues as in vitro cytotoxic agents","volume":"16","author":"Matesic","year":"2008","journal-title":"Bioorg Med Chem"},{"issue":"10","key":"R7-20240909","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1007\/s12272-011-1005-3","article-title":"Synthesis of novel isatin-thiazoline and isatin-benzimidazole conjugates as anti-breast cancer agents","volume":"34","author":"Taher","year":"2011","journal-title":"Arch Pharm Res"},{"issue":"4","key":"R8-20240909","doi-asserted-by":"crossref","first-page":"243","DOI":"10.2174\/157018008784619915","article-title":"Schiff bases of istain: Potential anti-leishmanial agents","volume":"5","author":"Khan","year":"2008","journal-title":"Lett Drug Des Discov"},{"issue":"5","key":"R9-20240909","doi-asserted-by":"crossref","first-page":"628","DOI":"10.3109\/14756366.2013.836641","article-title":"5-Nitroisatin-derived thiosemicarbazones: potential antileishmanial agents","volume":"29","author":"Pervez","year":"2014","journal-title":"J Enzyme Inhib Med Chem"},{"issue":"5","key":"R10-20240909","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.jsps.2019.04.003","article-title":"Synthesis, anticancer, apoptosis-inducing activities and EGFR and VEGFR2 assay mechanistic studies of 5, 5-diphenylimidazolidine-2, 4-dione derivatives: molecular docking studies","volume":"27","author":"Alkahtani","year":"2019","journal-title":"Saudi Pharm J"},{"key":"R11-20240909","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.molstruc.2019.04.122","article-title":"Synthesis and evaluation of new isatin-aminorhodanine hybrids as PIM1 and CLK1 kinase inhibitors","volume":"1192","author":"Khaldoun","year":"2019","journal-title":"J Mol Struct"},{"issue":"2","key":"R12-20240909","first-page":"9","article-title":"Design, molecular docking, synthesis and evaluation of new isatin derivatives bearing pyridine moiety as potential tyrosine kinase inhibitors","volume":"65","author":"Ibrahim","year":"2022","journal-title":"Egypt J Chem"},{"issue":"9","key":"R13-20240909","first-page":"1","article-title":"Isatin-hydrazones with multiple receptor tyrosine kinases (RTKs) inhibitory activity and in-silico binding mechanism","volume":"11","author":"Al-Salem","year":"2021","journal-title":"Appl Sci (Basel)"},{"issue":"7","key":"R14-20240909","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1021\/jm0204183","article-title":"Discovery of 5-[5-fluoro-2-oxo-1, 2-dihydroindol-(3Z)-ylidenemethyl]-2, 4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl) amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase","volume":"46","author":"Sun","year":"2003","journal-title":"J Med Chem"},{"key":"R15-20240909","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ejmech.2018.10.068","article-title":"Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents","volume":"162","author":"Eldehna","year":"2019","journal-title":"Eur J Med Chem"},{"issue":"3","key":"R16-20240909","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1248\/bpb.b17-00674","article-title":"Synthesis of novel class of N-alkyl-isatin-3-iminobenzoic acid derivatives and their biological activity in zebrafish embryos and human cancer cell lines","volume":"41","author":"Farooq","year":"2018","journal-title":"Biol Pharm Bull"},{"issue":"4","key":"R17-20240909","doi-asserted-by":"crossref","first-page":"397","DOI":"10.2174\/1871520610909040397","article-title":"Cytotoxic and anticancer activities of isatin and its derivatives: a comprehensive review from 2000-2008","volume":"9","author":"Vine","year":"2009","journal-title":"Anticancer Agents Med Chem"},{"key":"R18-20240909","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00044-010-9361-y","article-title":"Design, synthesis, and QSAR study of novel 2-(2, 3-dioxo-2, 3-dihydro-1H-indol-1-yl)-N-phenylacetamide derivatives as cytotoxic agents","volume":"20","author":"Modi","year":"2011","journal-title":"Med Chem Res"},{"issue":"2","key":"R19-20240909","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1734-1140(13)71007-7","article-title":"Biochemical and pharmacological characterization of isatin and its derivatives: from structure to activity","volume":"65","author":"Pakravan","year":"2013","journal-title":"Pharmacol Rep"},{"issue":"2","key":"R20-20240909","first-page":"151","article-title":"Biological targets for isatin and its analogues: implications for therapy","volume":"1","author":"Medvedev","year":"2007","journal-title":"Biologics"},{"issue":"20","key":"R21-20240909","doi-asserted-by":"crossref","first-page":"6006","DOI":"10.1016\/j.bmc.2011.08.044","article-title":"Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway","volume":"19","author":"Krishnegowda","year":"2011","journal-title":"Bioorg Med Chem"},{"issue":"3","key":"R22-20240909","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.neuint.2005.02.011","article-title":"Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells","volume":"47","author":"Igosheva","year":"2005","journal-title":"Neurochem Int"},{"issue":"19","key":"R23-20240909","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/molecules25194400","article-title":"A series of isatin-hydrazones with cytotoxic activity and CDK2 kinase inhibitory activity: a potential type II ATP competitive inhibitor","volume":"25","author":"Al-Salem","year":"2020","journal-title":"Molecules"},{"key":"R24-20240909","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00044-017-1781-5","article-title":"Design, synthesis and molecular docking of novel structural hybrids of substituted isatin based pyrazoline and thiadiazoline as antitumor agents","volume":"26","author":"Gangarapu","year":"2017","journal-title":"Med Chem Res"},{"key":"R25-20240909","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4103\/jrptps.JRPTPS_3_20","article-title":"Synthesis and evaluation of thiadiazole-based antileishmanial agents","volume":"9","author":"Hassanzadeh","year":"2020","journal-title":"J Rep Pharma Sci"},{"issue":"3","key":"R26-20240909","first-page":"171","article-title":"Synthesis and antioxidant evaluation of some novel ortho- hydroxypyridine-4-one iron chelators","volume":"7","author":"Mohammadpour","year":"2012","journal-title":"Res Pharm Sci"},{"issue":"5","key":"R27-20240909","doi-asserted-by":"crossref","first-page":"454","DOI":"10.4103\/1735-5362.297848","article-title":"Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds","volume":"15","author":"Hassanzadeh","year":"2020","journal-title":"Res Pharm Sci"},{"issue":"5","key":"R28-20240909","doi-asserted-by":"crossref","first-page":"408","DOI":"10.4103\/1735-5362.268201","article-title":"Synthesis and cytotoxic evaluation of some quinazolinone-5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates","volume":"14","author":"Hassanzadeh","year":"2019","journal-title":"Res Pharm Sci"},{"issue":"3","key":"R29-20240909","first-page":"51","article-title":"In vitro antileishmanial activity and apoptosis induction of Pleurotus ostreatus alcoholic extract on Leishmania major","volume":"4","author":"Ramezani","year":"2017","journal-title":"Res J Pharmacogn"},{"issue":"4","key":"R30-20240909","first-page":"228","article-title":"Synthesis, cytotoxic effect assessment and molecular docking studies of disubstituted thiadiazole including oxadiazole as hybrid component","volume":"42","author":"Hassanzadeh","year":"2022","journal-title":"Hacet Univ J Fac Pharm"},{"issue":"1","key":"R31-20240909","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1134\/S1070363218010085","article-title":"A study on hydrolytic stability of isatin N-Mannich bases","volume":"88","author":"Orlova","year":"2018","journal-title":"Russ J Gen Chem"},{"issue":"21","key":"R32-20240909","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1021\/jm0704189","article-title":"An investigation into the cytotoxicity and mode of action of some novel N-alky l-substituted isatins","volume":"50","author":"Vine","year":"2007","journal-title":"J Med Chem"},{"issue":"8","key":"R33-20240909","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4172\/2161-0444.1000194","article-title":"Molecular docking studies and ADME prediction of novel isatin analogs with potent anti-EGFR activity","volume":"4","author":"Ganguly","year":"2014","journal-title":"Med Chem (Los Angeles)"}],"container-title":["Research in Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/RPS.RPS_244_22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:28:48Z","timestamp":1787768928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/RPS.RPS_244_22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/rps.rps_244_22","relation":{},"ISSN":["1735-5362","1735-9414"],"issn-type":[{"value":"1735-5362","type":"print"},{"value":"1735-9414","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2022-12-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-17","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}