{"refrec":{"BRefID":257327,"RR":"<b>Frolova, L.; Magedov, I.; Romero, A.; Karki, M.; Otero, I.; Hayden, K.; Evdokimov, N.; Banuls, L.M.Y.; Rastogi, S.; Smith, W.; Lu, S.; Kiss, R.; Shuster, C.; Hamel, E.; Betancourt, T.; Rogelj, S.; Kornienko, A.</b> (2013). Exploring natural product chemistry and biology with multicomponent reactions. 5. Discovery of a novel tubulin-targeting scaffold derived from the rigidin family of marine alkaloids. <i>J. Med. Chem. 56(17)</i>: 6886-6900. <a href=\"https://dx.doi.org/10.1021/jm400711t\" target=\"_blank\">https://dx.doi.org/10.1021/jm400711t</a>","BEntID":249336,"PublicFlag":1,"CheckedFlag":1,"wosflag":1,"vabbflag":1,"RefStringPartII":". <i>J. Med. Chem. 56(17)</i>: 6886-6900. <a href=\"https://dx.doi.org/10.1021/jm400711t\" target=\"_blank\">https://dx.doi.org/10.1021/jm400711t</a>","DocTypID":8,"DocType":"Journal article","MarineFlag":1,"FreshFlag":0,"BrackishFlag":0,"TerrestrialFlag":0,"Authorstring":"Frolova, L.; Magedov, I.; Romero, A.; Karki, M.; Otero, I.; Hayden, K.; Evdokimov, N.; Banuls, L.M.Y.; Rastogi, S.; Smith, W.; Lu, S.; Kiss, R.; Shuster, C.; Hamel, E.; Betancourt, T.; Rogelj, S.; Kornienko, A.","OrigTitleTranslFlag":0,"Authorstringtrunc":"Frolova, L. <i>et al.</i>","Englishabstract":"We developed synthetic chemistry to access the marine alkaloid rigidins and over 40 synthetic analogues based on the 7-deazaxanthine, 7-deazaadenine, 7-deazapurine, and 7-deazahypoxanthine skeletons. Analogues based on the 7-deazahypoxanthine skeleton exhibited nanomolar potencies against cell lines representing cancers with dismal prognoses, tumor metastases, and multidrug resistant cells. Studies aimed at elucidating the mode(s) of action of the 7-deazahypoxanthines in cancer cells revealed that they inhibited in vitro tubulin polymerization and disorganized microtubules in live HeLa cells. Experiments evaluating the effects of the 7-deazahypoxanthines on the binding of [H-3]colchicine to tubulin identified the colchicine site on tubulin as the most likely target for these compounds in cancer cells. Because many microtubule-targeting compounds are successfully used to fight cancer in the clinic, we believe the new chemical class of antitubulin agents represented by the 7-deazahypoxanthine rigidin analogues have significant potential as new anticancer agents.","AbstractOtherLang":null,"BibLvlCode":"AS","StandardTitle":"Exploring natural product chemistry and biology with multicomponent reactions. 5. 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