title: Two new tryptophan derivatives from the seed kernels of Entada rheedei: effects on cell viability and HIV infectivity.
abstract: Two new tryptophan derivatives, N-sulfonyl-L-tryptophan (tryptorheedei A) (1) and 3-(N-sulfonylindolyl)-D-lactic acid (tryptorheedei B) (2) together with the known 5-O-β-D-glucopyranosyl-2-hydroxyphenylacetic acid (3), 1-O-methylglucopyranoside, entadamide A, homogentisic acid and 3-O-β-D-glucopyranosyl-β-sitosterol, were isolated from the seed kernels of Entada rheedei (Mimosaceae). Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry and by comparison with spectroscopic data reported in the literature. Compounds 1 and 2 showed no toxicity to TZM and Human PBMC cells. Both compounds 1 and 2 were found to promote early infection events in HIV, likely by inhibiting the enzyme indolamine 2,3-dioxygenase (IDO) and preventing tryptophan depletion. Inhibition of IDO acutely in HIV infection inhibits viral replication, but chronic activation of IDO leads to immune impairment in AIDS. IDO is also the gatekeeper enzyme for kynurenine metabolism, a pathway involved in serotonin and melatonin biosynthesis and the regulation of glutamate and dopamine levels in the brain. Therefore inhibition of IDO might explain both the reported medicinal and neuropsychiatric effects of E. rheedei.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
authors.forename: L K
authors.initials: LK
authors.lastname: Nzowa
authors.forename: R B
authors.initials: RB
authors.lastname: Teponno
authors.forename: L A
authors.initials: LA
authors.lastname: Tapondjou
authors.forename: L
authors.initials: L
authors.lastname: Verotta
authors.forename: Z
authors.initials: Z
authors.lastname: Liao
authors.forename: D
authors.initials: D
authors.lastname: Graham
authors.forename: M-C
authors.initials: MC
authors.lastname: Zink
authors.forename: L
authors.initials: L
authors.lastname: Barboni
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D007887:Fabaceae / Q000737:chemistry*; D018698:Glutamic Acid / Q000378:metabolism; D006678:HIV / Q000187:drug effects / Q000472:pathogenicity; D015658:HIV Infections / Q000201:enzymology / Q000821:virology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D007737:Kynurenine / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008550:Melatonin / Q000096:biosynthesis; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry; D012701:Serotonin / Q000096:biosynthesis; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010936:Plant Extracts; D011619:Psychotropic Drugs; C585628:tryptorheedei A; C585629:tryptorheedei B; D012701:Serotonin; D007737:Kynurenine; D018698:Glutamic Acid; D014364:Tryptophan; D008550:Melatonin; D004298:Dopamine
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