Four new tetrahydrofuran lignans,schpropinrins A-D(1-4),together with five known ones,were isolated from the leaves and stems of Schisandra propinqua var.sinensis.Their structures,including absolute configurations,wer...Four new tetrahydrofuran lignans,schpropinrins A-D(1-4),together with five known ones,were isolated from the leaves and stems of Schisandra propinqua var.sinensis.Their structures,including absolute configurations,were characterized by means of spectroscopic analysis and ECD calculation.Compounds 1-4 featured a ketal or hemiketal substructure at C-7 and all of the isolates were tested for their anti-HIV integrase activity.展开更多
Anti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type st...Anti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type steroids, named amotsterols A-D （1-4）, together with two known analogs. Among them, the most potent amotsterol D （4） exhibited anti-HIV activity against wild- type and some clinically relevant multidrug resistant HIV-I strains. Subsequent studies on its target identification through a proteomic approach found that compound 4 might target PKM2, a rate limiting enzyme ofglycolysis, in host cells to restrict HIV replication. The docking model of compound 4 to PKM2 showed that the two hydroxyl groups of 4 form hydrogen bonds with the two parallel Y390 in each subunit of PKM2 separately, and the ring C of 4 is sandwiched between the two parallel aromatic rings ofF26. The identified hit compound may have the potential to be further developed as a novel anti-HIVagent. These results demonstrated that an integrated approach, which combines new chemical structures and phenotypic screening with a proteomic approach, could not only identify novel HIV-1 inhibitors, but also elucidate the unknown targets of compound interactions in antiviral drug discovery.展开更多
基金the NSFC(No.20802082 and 30830115)the projects from the Chinese Academy of Sciences(KSCX2-EW-Q-10 and KSCX1-YW-R-24)+1 种基金the Major State Basic Research Development Program of China(No.2009CB522303 and 2009CB940900)the Natural Science Foundation of Yunnan Province(No.2012FB178)。
文摘Four new tetrahydrofuran lignans,schpropinrins A-D(1-4),together with five known ones,were isolated from the leaves and stems of Schisandra propinqua var.sinensis.Their structures,including absolute configurations,were characterized by means of spectroscopic analysis and ECD calculation.Compounds 1-4 featured a ketal or hemiketal substructure at C-7 and all of the isolates were tested for their anti-HIV integrase activity.
基金supported by the National Natural Science Foundation of China (21532007, U1302222)the "Personalized Medicines-Molecular Signature-based Drug Discovery and Development"+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12020321)the Canadian Institutes for Health Research (CIHR)
文摘Anti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type steroids, named amotsterols A-D （1-4）, together with two known analogs. Among them, the most potent amotsterol D （4） exhibited anti-HIV activity against wild- type and some clinically relevant multidrug resistant HIV-I strains. Subsequent studies on its target identification through a proteomic approach found that compound 4 might target PKM2, a rate limiting enzyme ofglycolysis, in host cells to restrict HIV replication. The docking model of compound 4 to PKM2 showed that the two hydroxyl groups of 4 form hydrogen bonds with the two parallel Y390 in each subunit of PKM2 separately, and the ring C of 4 is sandwiched between the two parallel aromatic rings ofF26. The identified hit compound may have the potential to be further developed as a novel anti-HIVagent. These results demonstrated that an integrated approach, which combines new chemical structures and phenotypic screening with a proteomic approach, could not only identify novel HIV-1 inhibitors, but also elucidate the unknown targets of compound interactions in antiviral drug discovery.
