80850-73-3Relevant articles and documents
Design, synthesis, and evaluation of novel mutual prodrugs (hybrid drugs) of all-trans-retinoic acid and histone deacetylase inhibitors with enhanced anticancer activities in breast and prostate cancer cells in vitro
Gediya, Lalji K.,Khandelwal, Aakanksha,Patel, Jyoti,Belosay, Aashvini,Sabnis, Gauri,Mehta, Jhalak,Purushottamachar, Puranik,Njar, Vincent C. O.
experimental part, p. 3895 - 3904 (2009/05/07)
Novel mutual prodrugs (MPs) of ATRA (all-trans-retinoic acid) and HDIs (histone deacetylase inhibitors) (10, 13, 17-19) connected via glycine acyloxyalkyl carbamate linker (AC linker) or through a benzyl ester linker (1,6-elimination linker) were rationally designed and synthesized. Most of our novel MPs were potent inhibitors of growth of several hormone-insensitive/drug resistant breast cancer cell lines and the hormone-insensitive PC-3 prostate cancer cell line. The novel MPs exhibited differential antiproliferative potencies in both MDA-MB-231 and PC-3 cell lines. Whereas 19 (VNLG/124) [4-(butanoyloxymethyl)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6, 6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoate] with a GI50 of 10 nM was the most potent MP versus the MDA-MB-231 cells, 13 (VNLG/66) [{N-[N-{2-[4-{[3-pyridylmethoxy)carbonyamino]-methyl}phenyl)carbonylamino] phenyl} carbamoylcarbamoyloxy}methyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6- trimethyl cyclohex-1-enyl)nona-2,4,6,8-tetraenoate] with a GI50 = 40 nM was the most potent versus the PC-3 cells. MP 19 exhibited the most benefit because its GI50 of 10 nM versus MDA-MB-231 cells was remarkably 1085-fold lower than that of parent ATRA and over 100000-fold lower than butyric acid (BA).
