Discovery of (E)-3-((Styrylsulfonyl) methyl) pyridine and (E)-2-((Styrylsulfonyl) methyl) pyridine Derivatives as Anticancer Agents: Synthesis, Structure–Activity Relationships, and Biological Activities

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dc.contributor.authorLu, T.
dc.contributor.authorGoh, A.W.
dc.contributor.authorYu, M.
dc.contributor.authorAdams, J.
dc.contributor.authorLam, F.
dc.contributor.authorTeo, T.
dc.contributor.authorLi, P.
dc.contributor.authorNoll, B.
dc.contributor.authorZhong, L.
dc.contributor.authorDiab, S.
dc.contributor.authorChahrour, O.
dc.contributor.authorHu, A.
dc.contributor.authorAbbas, A.
dc.contributor.authorLiu, X.
dc.contributor.authorHuang, S.
dc.contributor.authorSumby, C.
dc.contributor.authorMilne, R.
dc.contributor.authorMidgley, C.
dc.contributor.authorWang, S.
dc.date.issued2014
dc.description.abstractON01910.Na is a highly effective anticancer agent that induces mitotic arrest and apoptosis. Clinical studies with ON01910 in cancer patients have shown efficacy along with an impressive safety profile. While ON01910 is highly active against cancer cells, it has a low oral availability and requires continuous intravenous infusion or multiple gram doses to ensure sufficient drug exposure for biological activity in patients. We have identified two novel series of styrylsulfonyl-methylpyridines. Lead compounds 8, 9a, 18 and 19a are highly potent mitotic inhibitors and selectively cytotoxic to cancer cells. Impressively, these compounds possess excellent pharmaceutical properties and two lead drug candidates 9a and 18 demonstrated antitumor activities in animal models.
dc.description.statementofresponsibilityTiangong Lu, Aik Wye Goh, Mingfeng Yu, Julian Adams, Frankie Lam, Theodosia Teo, Peng Li, Ben Noll, Longjin Zhong, Sarah Diab, Osama Chahrour, Anran Hu, Abdullahi Y. Abbas, Xiangrui Liu, Shiliang Huang, Christopher J. Sumby, Robert Milne, Carol Midgley, and Shudong Wang
dc.identifier.citationJournal of Medicinal Chemistry, 2014; 57(6):2275-2291
dc.identifier.doi10.1021/jm4019614
dc.identifier.issn0022-2623
dc.identifier.issn1520-4804
dc.identifier.orcidSumby, C. [0000-0002-9713-9599]
dc.identifier.urihttp://hdl.handle.net/2440/81860
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.source.urihttps://doi.org/10.1021/jm4019614
dc.subjectCell Line, Tumor
dc.subjectMicrosomes, Liver
dc.subjectAnimals
dc.subjectMice
dc.subjectRats
dc.subjectSulfonamides
dc.subjectAminopyridines
dc.subjectStyrenes
dc.subjectSulfones
dc.subjectGlycine
dc.subjectAnnexin A5
dc.subjectAntineoplastic Agents
dc.subjectIndicators and Reagents
dc.subjectCrystallography, X-Ray
dc.subjectMagnetic Resonance Spectroscopy
dc.subjectArea Under Curve
dc.subjectXenograft Model Antitumor Assays
dc.subjectCell Cycle
dc.subjectApoptosis
dc.subjectCell Proliferation
dc.subjectStructure-Activity Relationship
dc.subjectBiological Availability
dc.subjectDrug Design
dc.subjectModels, Molecular
dc.subjectHalf-Life
dc.subjectMass Spectrometry
dc.subjectDrug Discovery
dc.subjectKaplan-Meier Estimate
dc.titleDiscovery of (E)-3-((Styrylsulfonyl) methyl) pyridine and (E)-2-((Styrylsulfonyl) methyl) pyridine Derivatives as Anticancer Agents: Synthesis, Structure–Activity Relationships, and Biological Activities
dc.typeJournal article
pubs.publication-statusPublished

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