{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:57:10Z","timestamp":1785527830710,"version":"3.56.0"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1016\/j.bioorg.2020.103865","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T11:32:54Z","timestamp":1587382374000},"page":"103865","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Dispiropyrrolidine tethered piperidone heterocyclic hybrids with broad-spectrum antifungal activity against Candida albicans and Cryptococcus neoformans"],"prefix":"10.1016","volume":"100","author":[{"given":"Sarah","family":"Lawson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natarajan","family":"Arumugam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman I.","family":"Almansour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Suresh Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar","family":"Thangamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2020.103865_b0005","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3410\/M3-14","article-title":"Emerging fungal infections in immunocompromised patients","volume":"3","author":"Low","year":"2011","journal-title":"F1000 Med. Rep."},{"key":"10.1016\/j.bioorg.2020.103865_b0010","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-micro-091014-104330","article-title":"Candida albicans biofilms and human disease","volume":"69","author":"Nobile","year":"2015","journal-title":"Annu. Rev. Microbiol."},{"issue":"4","key":"10.1016\/j.bioorg.2020.103865_b0015","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1128\/JCM.42.4.1519-1527.2004","article-title":"Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program","volume":"42","author":"Hajjeh","year":"2004","journal-title":"J. Clin. Microbiol."},{"issue":"1","key":"10.1016\/j.bioorg.2020.103865_b0020","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1128\/CMR.00029-06","article-title":"Epidemiology of invasive candidiasis: a persistent public health problem","volume":"20","author":"Pfaller","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.bioorg.2020.103865_b0025","doi-asserted-by":"crossref","unstructured":"S. Tsay, S. Williams, Y. Mu, et al., National Burden of Candidemia, United States, 2017. Open Forum Infectious Diseases. 2018;5:S142\u2013S143.","DOI":"10.1093\/ofid\/ofy210.374"},{"issue":"3","key":"10.1016\/j.bioorg.2020.103865_b0030","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1086\/421946","article-title":"Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study","volume":"39","author":"Wisplinghoff","year":"2004","journal-title":"Clin. Infect. Diseases: Off. Publication Infect. Diseases Soc. Am."},{"issue":"7","key":"10.1016\/j.bioorg.2020.103865_b0035","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s10096-006-0159-2","article-title":"Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies","volume":"25","author":"Falagas","year":"2006","journal-title":"Eur. J. Clin. Microb. Infect. Diseases: Off. Publ. Eur. Soc. Clin. Microbiol."},{"issue":"5","key":"10.1016\/j.bioorg.2020.103865_b0040","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jmii.2010.08.010","article-title":"Candida albicans versus non-albicans bloodstream infections: the comparison of risk factors and outcome","volume":"44","author":"Chi","year":"2011","journal-title":"J. Microbiol. Immunol. Infect."},{"issue":"6","key":"10.1016\/j.bioorg.2020.103865_b0045","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1093\/clinids\/17.6.1018","article-title":"Fluconazole-resistant Candida albicans","volume":"17","author":"Boken","year":"1993","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.bioorg.2020.103865_b0050","doi-asserted-by":"crossref","unstructured":"S.R. Lockhart, N. Iqbal, A.A. Cleveland, et al., 2012. Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011. J Clin Microbiol. 50(11) (2012) 3435\u20133442.","DOI":"10.1128\/JCM.01283-12"},{"issue":"3","key":"10.1016\/j.bioorg.2020.103865_b0055","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s12275-016-5628-4","article-title":"The development of fluconazole resistance in Candida albicans - an example of microevolution of a fungal pathogen","volume":"54","author":"Morschhauser","year":"2016","journal-title":"J Microbiol."},{"key":"10.1016\/j.bioorg.2020.103865_b0060","first-page":"2173","article-title":"Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species","volume":"7","author":"Whaley","year":"2016","journal-title":"Front Microbiol."},{"issue":"6","key":"10.1016\/j.bioorg.2020.103865_b0065","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1128\/AAC.46.6.1704-1713.2002","article-title":"Resistance mechanisms in clinical isolates of Candida albicans","volume":"46","author":"White","year":"2002","journal-title":"Antimicrob Agents Chemother."},{"issue":"11","key":"10.1016\/j.bioorg.2020.103865_b0070","first-page":"B4698","article-title":"Candida and candidaemia. Susceptibility and epidemiology","volume":"60","author":"Arendrup","year":"2013","journal-title":"Dan. Med. J."},{"issue":"4","key":"10.1016\/j.bioorg.2020.103865_b0075","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.diagmicrobio.2012.10.003","article-title":"Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance(R)) registry, 2004\u20132008","volume":"74","author":"Pfaller","year":"2012","journal-title":"Diagn Microbiol Infect Dis."},{"key":"10.1016\/j.bioorg.2020.103865_b0080","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.ejmech.2014.06.056","article-title":"Spirooxindoles: promising scaffolds for anticancer agents","volume":"97","author":"Yu","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103865_b0085","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bmcl.2014.10.099","article-title":"Facile and diastereoselective synthesis of 3,2\u2032-spiropyrrolidine-oxindoles derivatives, their molecular docking and antiproliferative activities","volume":"25","author":"Kathirvelan","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2020.103865_b0090","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejmech.2013.12.027","article-title":"Novel spirooxindole-pyrrolidine compounds: synthesis, anticancer and molecular docking studies","volume":"74","author":"Arun","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103865_b0095","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1039\/c0md00239a","article-title":"Antimycobacterial activity of spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrids obtained by a three-component regio- and stereoselective 1,3-dipolar cycloaddition","volume":"2","author":"Rajesh","year":"2011","journal-title":"Med. Chem. Commun."},{"key":"10.1016\/j.bioorg.2020.103865_b0100","doi-asserted-by":"crossref","unstructured":"G. Bhaskar, Y. Arun, C. Balachandran, C. Saikumar, P.T. Synthesis of novel spirooxindole derivatives by one pot multicomponent reaction and their antimicrobial activity, Eur. J. Med. Chem. 51 (2012) 79\u201391.","DOI":"10.1016\/j.ejmech.2012.02.024"},{"key":"10.1016\/j.bioorg.2020.103865_b0105","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.1016\/j.bmcl.2013.04.053","article-title":"A facile synthesis, anti-inflammatory and analgesic activity of isoxazolyl-2,3-dihydrospiro[benzo[f]isoindole-1,3'-indoline]-2',4,9-triones","volume":"23","author":"Rajanarendar","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2020.103865_b0110","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1021\/jm00229a007","article-title":"Oxindole-3-spiropyrrolidines and -piperidines. Synthesis and local anesthetic activity","volume":"19","author":"Kornet","year":"1976","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103865_b0115","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1016\/j.bmc.2019.03.058","article-title":"Dispiropyrrolidinyl-piperidone embedded indeno[1,2-b]quinoxaline heterocyclic hybrids: Synthesis, cholinesterase inhibitory activity and their molecular docking simulation","volume":"27","author":"Arumugam","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103865_b0120","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.bmcl.2014.02.019","article-title":"Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors","volume":"24","author":"Kia","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2020.103865_b0125","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1016\/j.bmcl.2013.03.027","article-title":"A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole\u2013pyrrolizine\u2013piperidine hybrids","volume":"23","author":"Kia","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2020.103865_b0130","unstructured":"A.I. Almansour, N. Arumugam, et al., Anticancer agents. In: US 9,873,699B1; US patent 2018."},{"key":"10.1016\/j.bioorg.2020.103865_b0135","unstructured":"A.I. Almansour, N. Arumugam, R. Suresh Kumar, et al. Anticancer agents. In: US patent US 9,486,444 B1 US patent 2016."},{"key":"10.1016\/j.bioorg.2020.103865_b0140","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1021\/jm0002580","volume":"44","author":"Dimmock","year":"2001","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103865_b0145","unstructured":"Crystallographic data (including structure factors) for spiropyrrolidine 6i in this article have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1007382. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk]."},{"issue":"10","key":"10.1016\/j.bioorg.2020.103865_b0150","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.3390\/molecules24101962","article-title":"Domino multicomponent approach for the synthesis of functionalized spiro-indeno[1,2-b]quinoxalineeterocyclic hybrids and their antimicrobial activity, synergistic effect and molecular docking simulation","volume":"24","author":"Almansour","year":"2019","journal-title":"Molecules"},{"issue":"3","key":"10.1016\/j.bioorg.2020.103865_b0155","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/fty038","article-title":"Secondary bile acids inhibit Candida albicans growth and morphogenesis","volume":"76","author":"Guinan","year":"2018","journal-title":"Pathog Dis."},{"issue":"5","key":"10.1016\/j.bioorg.2020.103865_b0160","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.bmcl.2019.01.006","article-title":"Benzimidazole tethered pyrrolo[3,4-b]quinoline with broad-spectrum activity against fungal pathogens","volume":"29","author":"Villa","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"1","key":"10.1016\/j.bioorg.2020.103865_b0165","article-title":"Candida albicans Hyphae: from growth initiation to invasion","volume":"4","author":"Desai","year":"2018","journal-title":"J. Fungi. (Basel)"},{"issue":"2","key":"10.1016\/j.bioorg.2020.103865_b0170","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1080\/21505594.2016.1197444","article-title":"Targeting Candida albicans filamentation for antifungal drug development","volume":"8","author":"Vila","year":"2017","journal-title":"Virulence"},{"issue":"1","key":"10.1016\/j.bioorg.2020.103865_b0175","first-page":"8872","article-title":"Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids correlate with increased gastrointestinal colonization of Candida albicans","volume":"9","author":"Guinan","year":"2019","journal-title":"SciRep."},{"issue":"3","key":"10.1016\/j.bioorg.2020.103865_b0180","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1439-0507.2011.02076.x","article-title":"Antifungal susceptibility of Candida albicans in biofilms","volume":"55","author":"Tobudic","year":"2012","journal-title":"Mycoses"},{"issue":"4","key":"10.1016\/j.bioorg.2020.103865_b0185","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.MB-0020-2015","article-title":"Candida biofilms: development, architecture, and resistance","volume":"3","author":"Chandra","year":"2015","journal-title":"Microbiol Spectr."},{"issue":"4","key":"10.1016\/j.bioorg.2020.103865_b0190","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00294-013-0400-3","article-title":"Recent insights into Candida albicans biofilm resistance mechanisms","volume":"59","author":"Mathe","year":"2013","journal-title":"Curr. Genet."},{"key":"10.1016\/j.bioorg.2020.103865_b0200","doi-asserted-by":"crossref","unstructured":"S. Thangamani, H.E. Eldesouky, H. Mohammad, et al., Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells, Biochim Biophys Acta Gen Subj. 1861(1 Pt A) (2017) 3002\u20133010.","DOI":"10.1016\/j.bbagen.2016.09.029"},{"key":"10.1016\/j.bioorg.2020.103865_b0205","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fcimb.2017.00004","article-title":"Repurposing approach identifies auranofin with broad spectrum antifungal activity that targets Mia40-Erv1 pathway","volume":"7","author":"Thangamani","year":"2017","journal-title":"Front Cell Infect Microbiol."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206820300511?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206820300511?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T07:59:14Z","timestamp":1758614354000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206820300511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":40,"alternative-id":["S0045206820300511"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.103865","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dispiropyrrolidine tethered piperidone heterocyclic hybrids with broad-spectrum antifungal activity against Candida albicans and Cryptococcus neoformans","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.103865","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"103865"}}