Baculiferins A-O, O-sulfated pyrrole alkaloids with anti-HIV-1 activity, from the Chinese marine sponge Iotrochota baculifera.
Fifteen new DOPA-derived pyrrole alkaloids, named baculiferins A-O (2-16), were isolated from the Chinese marine sponge Iotrochota baculifera, together with the known alkaloids purpurone (1) and ningalin A (17). Most of the new compounds contain one to three O-sulfate units. Their structures were determined by extensive spectroscopic analysis including (1)H and (13)C NMR (COSY, HMQC, HMBC) and ESIMS data. A possible pathway for the biosynthetic origin of the isolated alkaloids is proposed, in which DOPA is assumed to be a joint biogenetic precursor. Baculiferins C, E-H, and K-N (4, 6-9, 12-15) were found to be potent inhibitors against the HIV-1 IIIB virus in both, MT4 and MAGI cells. Additional bioassay revealed that baculiferins could dramatically bind to the HIV-1 target proteins Vif, APOBEC3G, and gp41, for which structure-activity relationships are discussed.
Fan
Guotao
G
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, People's Republic of China.
Li
Zelin
Z
Shen
Shi
S
Zeng
Yi
Y
Yang
Yishu
Y
Xu
Minjuang
M
Bruhn
Torsten
T
Bruhn
Heike
H
Morschhäuser
Joachim
J
Bringmann
Gerhard
G
Lin
Wenhan
W
D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D002681:China; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D011161:Porifera / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors / Q000378:metabolism
D000470:Alkaloids; D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D011758:Pyrroles; D013431:Sulfates; D014764:Viral Proteins; C514787:gp41 protein, Human immunodeficiency virus 1; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1