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dc.contributor.authorDasaria, Ramesh ( )
dc.contributor.authorBlauz, Andrzej ( Orcid Icon 0000-0002-8037-0268 )
dc.contributor.authorMedellin, Derek C. ( )
dc.contributor.authorKassim, Roaa M. ( )
dc.contributor.authorViera, Carlos ( )
dc.contributor.authorSantarosa, Maximo ( )
dc.contributor.authorTurner, Danielle ( )
dc.contributor.authorvan der Westhuyzen, Alet E. ( )
dc.contributor.authorvan Otterlo, Willem ( Orcid Icon 0000-0002-3300-6463 )
dc.contributor.authorOlivas, Taryn ( Orcid Icon 0000-0003-0965-2139 )
dc.contributor.authorYildiz, Tugba ( Orcid Icon 0000-0002-9253-0919 )
dc.contributor.authorBetancourt, Tania ( )
dc.contributor.authorShuster, Charles B. ( )
dc.contributor.authorRogelj, Snezna ( )
dc.contributor.authorRychlik, Blazej ( Orcid Icon 0000-0001-8928-5900 )
dc.contributor.authorHudnall, Todd W. ( Orcid Icon 0000-0002-9260-2986 )
dc.contributor.authorFrolova, Liliya V. ( )
dc.contributor.authorKornienko, Alexander ( )
dc.date.accessioned2020-03-13T14:32:40Z
dc.date.available2020-03-13T14:32:40Z
dc.date.issued2019-02-05
dc.identifier.citationDasari, R., Blauz, A., Medellin, D. C., Kassim, R. M., Viera, C., Santarosa, M., Turner, D., van der Westhuyzen, A. E., van Otterlo, W. A. L., Olivas, T., Yildiz, T., Betancourt, T., Shuster, C. B., Rogelj, S., Rychlik, B., Hudnall, T., Frolova, L. V., Kornienko, A. (2019). Microtubule-targeting 7-deazahypoxanthines derived from marine alkaloid rigidins: Exploration of the N3 and N9 positions and interaction with multidrug-resistance proteins. ChemMedChem, 14(3), pp. 322–333.en_US
dc.identifier.issn1860-7187
dc.identifier.urihttps://digital.library.txstate.edu/handle/10877/9442
dc.description.abstractOur laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure-activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents.en_US
dc.formatText
dc.format.extent25 pages
dc.format.medium1 file (.pdf)
dc.language.isoen
dc.publisherJohn Wiley and Sons Ltden_US
dc.sourceChemMedChem, 2019, Vol. 14, No. 3, pp. 322–333.
dc.subject7-deazapurinesen_US
dc.subjectAlkaloids
dc.subjectAntitumor agents
dc.subjectDrug discovery
dc.subjectPyrrolo[2,3-d]pyrimidines
dc.titleMicrotubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins: Exploration of the N3 and N9 Positions and Interaction with Multi-Drug Resistance Proteinsen_US
txstate.documenttypeArticle
dc.description.versionThis is the accepted manuscript version of an article published in ChemMedChem.
dc.identifier.doihttps://doi.org/10.1002/cmdc.201800658
txstate.departmentChemistry and Biochemistry


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