Synthesis and structure-activity relationship studies of 4,11-diaminonaphtho[2,3-f]indole-5,10-diones

Bioorganic & Medicinal Chemistry
Andrey E ShchekotikhinMaria N Preobrazhenskaya

Abstract

We describe the synthesis of derivatives of 4,11-diaminonaphtho[2,3-f]indole-5,10-dione and their cytotoxicity for human tumor cells that express major determinants of altered anticancer drug response, the efflux pump P-glycoprotein, and non-functional p53. Nucleophilic substitution of methoxy groups in 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione with various ethylenediamines yielded the derivatives of 4,11-diaminonaphtho[2,3-f]indole-5,10-dione, the indole containing analogues of the antitumor agent ametantrone. The cytotoxicity of novel compounds for multidrug resistant, P-glycoprotein-expressing tumor cells is highly dependent on the N-substituent at the terminal amino group of the ethylenediamine moiety. Whereas p53 null colon carcinoma cells were less sensitive to the reference drug doxorubicin than their counterparts with wild type p53, the majority of novel naphthoindole derivatives were equally potent for both cell lines, regardless of the p53 status.

References

Nov 25, 2005·Current Drug Delivery·Hristos GlavinasBalázs Sarkadi

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Citations

Dec 2, 2008·Bulletin of Experimental Biology and Medicine·L G DezhenkovaA A Shtil
Feb 10, 2012·The Journal of Antibiotics·Lyudmila N LysenkovaMaria N Preobrazhenskaya
Feb 2, 2012·Journal of Biomolecular Structure & Dynamics·Shirlene Jackson Beckford, Dabney W Dixon
Dec 3, 2014·European Journal of Medicinal Chemistry·Gheorghe Roman
Jul 26, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Siti Mariam Mohd NorSiti Fadilah Juhan
Sep 23, 2014·European Journal of Medicinal Chemistry·Andrey E ShchekotikhinMaria N Preobrazhenskaya
Jun 7, 2007·Organic & Biomolecular Chemistry·Stephen G DaviesSteven M Toms
Dec 24, 2019·Current Topics in Medicinal Chemistry·Talita Odriane Custodio LeiteAnna Claudia Cunha

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