New antiinfective and human 5-HT2 receptor binding natural and semisynthetic compounds from the Jamaican sponge Smenospongia aurea.
In addition to the sesquiterpene-phenol aureols (1), 6'-chloroaureol (2), and aureol acetate (3), eight indole alkaloids including the new N-3'-ethylaplysinopsin (9) have been isolated from the Jamaican sponge Smenospongia aurea. Makaluvamine O (10), a new member of the pyrroloiminoquinone class, was also isolated. The structures were characterized by spectroscopic methods, and two new derivatives of aureol were prepared to optimize the biological activity. Aureol N,N-dimethyl thiocarbamate (1a) and 6-bromoaplysinopsin (7) exhibit significant antimalarial and antimycobacterial activity in vitro. Compound 6 showed activity against the Plasmodium enzyme plasmepsin II. The 6-bromo-2'-de-N-methylaplysinopsin (6), 6-bromoaplysinopsin (7), and N-3'-ethylaplysinopsin (9) displaced high-affinity [(3)H]antagonist ligands from cloned human serotonin 5-HT(2) receptor subtypes, whereas the other compounds tested did not. Remarkably, the 6-bromo-2'-de-N-methylaplysinopsin (6) showed a > 40-fold selectivity for the 5-HT(2C) subtype over the 5-HT(2A) subtype.
Hu
Jin-Feng
JF
Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, USA.
Schetz
John A
JA
Kelly
Michelle
M
Peng
Jiang-Nan
JN
Ang
Kenny K H
KK
Flotow
Horst
H
Leong
Chung Yan
CY
Ng
Siew Bee
SB
Buss
Antony D
AD
Wilkins
Scott P
SP
Hamann
Mark T
MT
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007563:Jamaica; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D015800:Protozoan Proteins; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
C455541:6'-chloroaureol; C455545:6-bromo-2'-de-N-methylaplysinopsin; D000890:Anti-Infective Agents; D000962:Antimalarials; D026121:Indole Alkaloids; C455543:N-3'-ethylaplysinopsin; D015800:Protozoan Proteins; D011758:Pyrroles; D011809:Quinones; D011985:Receptors, Serotonin; D012717:Sesquiterpenes; C455540:aureol; C455542:aureol acetate; C455544:makaluvamine O; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II