1243216-26-3Relevant articles and documents
Efficient synthesis and biological evaluation of demethyl geranylgeranoic acid derivatives
Wada, Akimori,Wang, Fei,Suhara, Yoshitomo,Yamano, Yumiko,Okitsu, Takashi,Nakagawa, Kimie,Okano, Toshio
experimental part, p. 5795 - 5806 (2010/09/18)
Synthetic retinoids have generated in the fields of dermatology and oncology due to their potent anti-proliferative and differentiation activities. We efficiently synthesized different demethyl geranylgeranoic acid (GGA) analogs, and evaluated their biological activities. Among the demethyl analogs synthesized, 3-demethyl derivative exhibited the highest anti-proliferative activity in HL-60 cells. In addition, a 3-demethyl derivative induced apoptosis more potently than 9Z-retinoic acid. These activities were due to the high binding affinity of 3-demethyl derivative for retinoid receptors. We found that, in a conjugated polyene system combined with a methyl substituent, the position of the methyl played an important role in the regulation of gene transcription and apoptosis-inducing activity. These results provided useful information on the structure-activity relationships of GGA derivatives that function as acyclic retinoic acid analogs. This information is likely to be useful in the development of new anti-cancer drugs.
