Halogenated analogs of 1'-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action.
In the course of search for the robust analogs of 1'-acetoxychavicol acetate (ACA, 1), the Rev-export inhibitor from the medicinal plant Alpinia galanga, we clarified formation of the quinone methide intermediate ii to be essential for exerting the inhibitory activity of 1. Based on this mechanism of action, the rational design from the MO calculation of the conclusive activation energy to ii resulted in the four halogenated analogs with more potent activity than ACA (1). In particular, the difluoroanalog 20d exhibited approximately four-fold potent activity as compared with 1.
Tamura
Satoru
S
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Shiomi
Atsushi
A
Kimura
Tominori
T
Murakami
Nobutoshi
N
D032429:Alpinia / Q000737:chemistry*; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D015757:Genes, rev / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D001592:Benzyl Alcohols; D006846:Hydrocarbons, Halogenated; D010936:Plant Extracts; C047948:1'-acetoxychavicol acetate