Studies On The Anti-HIV Leading Compounds From Torreya Grandis Cv. Merrilli And Structure Modifications

Human Immunodeficiency Virus(HIV), which is severely harmful to humanhealth, occurs frequently and is widely seen around the world. There are more than 42million HIV carriers all over the world, and more than 1 million ones in our country.At present, the lack of effective anti-HIV drugs is still a severe problem in clinicalpractice because of the HIV variation. The development of new drugs and novel leadcompounds from nature plants enables a promising future in the chemotherapy of thediseases. Torreya grandis cv. Merrilli, a kind of plant that belongs to the genus of Torreya,is native to and found only in Zhuji, Zhejiang province. In the previous study, elevencompounds from the plant were obtained and identified with modernchromotographicandspectroscopic techniques, i.e. Two novel compounds according to the best of ourknowledge: 12 – deoxyl - 18 - carboxyl-nimbidiol ( TG – 08 ), ( 7, 8 - cis - 8, 8' -trans )- 2', 4' - dihydroxyl - 3, 5- dimethoxy - lariciresinol ( TG – 10 ). Sixcompounds are first reported from the species: 18-oxoferruginol ( TG – 02 ), 18 -hydroxylferruginol ( TG – 03 ), hinokiol ( TG – 04 ) , 4-epiagathadial ( TG – 05 ) ,18 – carboxyl - 16, l7 - pimaradien ( TG – 06 ), pinonesinol ( TG – 09 ),dihydrodehydrodiconiferylalcohol ( TG – 11 ). Torreyagrandate was found to presentinhibition of replication of human immunodeficiency virus in vitro, and its structurewas novel compared with clinical using drugs. In order to study the relationshipbetween the structures of TG-01 and its derivatives, and to find new compounds withanti-HIV effect, nineteen torreyagrandate analogues with 12-ether and 18-polargroups were designed and synthesized. The structures of all compounds weredeveloped by MS, HNMR, 1 13CNMR, etc. All of the title compounds are firstreported. Preliminary screening of TGM-1~19 and TG-06 by HIV-1 IN, HIV-1 PR andHIV-1 RT bioassay methods, four compounds showed HIV protease inhibition i.e.TGM-16,17,18 and TG-06. The possible relationship between structures and their 4第二军医大学 香榧中抗艾滋病病毒先导化合物的研究和结构修饰anti-HIV activities was analyzed.