New manzamine alkaloids with activity against infectious and tropical parasitic diseases from an Indonesian sponge.
Eleven manzamine type alkaloids, two beta-carbolines, and five nucleosides have been isolated from an Indonesian sponge. Among these are the previously characterized 12,34-oxamanzamine A, 12,34-oxamanzamine E, manzamine A (1), 8-hydroxymanzamine A, 6-deoxymanzamine X, manzamine E (2), manzamine X, manzamine F (4), norharman, thymine, 2',3'-didehydro-2',3'-dideoxyuridine, uracil, thymidine, and 2'-deoxyuridine. The structures for the five new compounds have been assigned as 32,33-dihydro-31-hydroxymanzamine A (3), 32,33-dihydro-6-hydroxymanzamine A-35-one (5), des-N-methylxestomanzamine A (6), 32,33-dihydro-6,31-dihydroxymanzamine A (7), and 1,2,3,4-tetrahydronorharman-1-one (8), on the basis of NMR and X-ray data. The bioactivity and SAR of the manzamines against malaria, TB, and leishmania are also presented. The structural revision of two previously reported pyrazoles as uracil and thymine is also discussed.
Rao
Karumanchi V
KV
The Department of Pharmacognosy and National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Santarsiero
Bernard D
BD
Mesecar
Andrew D
AD
Schinazi
Raymond F
RF
Tekwani
Babu L
BL
Hamann
Mark T
MT
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002227:Carbazoles; D002243:Carbolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018360:Crystallography, X-Ray; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007214:Indonesia; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009705:Nucleosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism
D000470:Alkaloids; D019380:Anti-HIV Agents; D000981:Antiprotozoal Agents; D002227:Carbazoles; D002243:Carbolines; D007211:Indoles; D009705:Nucleosides; D011758:Pyrroles; C078290:manzamine A