Journal of Medicinal Chemistry p. 1900 - 1914 (2015)
Update date:2022-08-15
Topics:
Mbatia, Hannah W.
Ramalingam, Senthilmurugan
Ramamurthy, Vidya P.
Martin, Marlena S.
Kwegyir-Afful, Andrew K.
Njar, Vincent C. O.
The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most potent compounds against a variety of human breast and prostate cancer (BC/PC) cell lines were compounds 16 (VNHM-1-66), 20 (VNHM-1-81), and 22 (VNHM-1-73). In these cell lines, the compounds induce Mnk1/2 degradation to substantially suppress eIF4E phosphorylation. In PC cells, the compounds induce degradation of both full-length androgen receptor (fAR) and splice variant AR (AR-V7) to inhibit AR transcriptional activity. More importantly, VNHM-1-81 has strong in vivo antibreast and antiprostate cancer activities, while VNHM-1-73 exhibited strong in vivo antibreast cancer activity, with no apparent host toxicity. Clearly, these lead compounds are strong candidates for development for the treatments of human breast and prostate cancers.
View MoreZhejiang Chemicals Import & Export Corporation (ZHECHEM)
Contact:+86-571-87046953
Address:No. 37, Qingchun Road
Tianjin Anda North Industrial & Business Co.Ltd.
Contact:86-22-24999306
Address:No.11 Erwei Road,Dongli Development Area,Tianjin,China
JOY (TIANJIN) TECHNOLOGY AND DEVELOPMENT CO., LTD.
Contact:+86-22-66666666
Address:Tianjin
Dezhou Longteng Chemical Co., Ltd.
website:http://www.sodium-methoxide.cn/
Contact:0086-18866052283
Address:Xinhua Industrial Zone, Dezhou City, Shandong Province, China
Tianjin Ji Ping Jia Chemical Co., Ltd.
Contact:18622448868
Address:tianjin
Doi:10.1016/S0020-1693(00)00196-1
(2000)Doi:10.1246/cl.1982.587
(1982)Doi:10.1021/jo01318a017
(1979)Doi:10.1080/10426500108040598
(2001)Doi:10.1016/j.poly.2003.10.013
(2004)Doi:10.1016/S0022-328X(00)84978-5
(1973)