Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity.
Several new phorbol derivatives having ethereal substituents at the 12-position were synthesized and subjected to biological evaluation to find new candidates of an anti-HIV agent. Among them, 12-O-(methoxymethyl)phorbol 13-decanoate showed potent inhibitory activity against infection of HIV-1 in MT-4 cells (EC50: 1.3 ng/mL) and relatively low cytotoxicity (CC50: 8.3 microg/mL). This compound was also found to have sufficient stability in mouse plasma compared with the corresponding 12-acetate derivative, which was an equipotent HIV-1 inhibitor, but with an activity that decreased considerably after plasma treatment.
Matsuya
Yuji
Y
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0914, Japan.
Yu
Zhong
Z
Yamamoto
Naoki
N
Mori
Masao
M
Saito
Haruo
H
Takeuchi
Makoto
M
Ito
Mamiko
M
Nemoto
Hideo
H
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010704:Phorbols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D019380:Anti-HIV Agents; D010704:Phorbols