- Discovery, Total Synthesis, and SAR of Anaenamides A and B: Anticancer Cyanobacterial Depsipeptides with a Chlorinated Pharmacophore
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New modified depsipeptides and geometric isomers, termed anaenamides A (1a) and B (1b), along with the presumptive biosynthetic intermediate, anaenoic acid (2), were discovered from a marine cyanobacterium from Guam. Structures were confirmed by total synthesis. The alkylsalicylic acid fragment and the C-terminal α-chlorinated α,β-unsaturated ester are novelties in cyanobacterial natural products. Cancer cell viability assays indicated that the C-terminal unit serves as the pharmacophore and that the double-bond geometry impacts the cytotoxicity.
- Brumley, David A.,Chen, Qi-Yin,Gunasekera, Sarath P.,Luesch, Hendrik,Paul, Valerie J.
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supporting information
p. 4235 - 4239
(2020/06/27)
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- Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi
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Chagas' disease, a parasitic infection caused by the flagellate protozoan Trypanosoma cruzi, is a major public health problem affecting millions of individuals in Latin America. On the basis of the essential role in the life cycle of T. cruzi, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been considered an attractive target for the development of novel antitrypanosomatid agents. In the present work, we describe the inhibitory effects of a small library of natural and synthetic anacardic acid derivatives against the target enzyme. The most potent inhibitors, 6-n-pentadecyl- (1) and 6-n-dodecylsalicilic acids (10e), have IC50 values of 28 and 55 μM, respectively. The inhibition was not reversed or prevented by the addition of Triton X-100, indicating that aggregate-based inhibition did not occur. In addition, detailed mechanistic characterization of the effects of these compounds on the T. cruzi GAPDH-catalyzed reaction showed clear noncompetitive inhibition with respect to both substrate and cofactor.
- Pereira, Junia M.,Severino, Richele P.,Vieira, Paulo C.,Fernandes, Joao B.,da Silva, M. Fatima G.F.,Zottis, Aderson,Andricopulo, Adriano D.,Oliva, Glaucius,Correa, Arlene G.
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p. 8889 - 8895
(2008/12/23)
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- Synthetic studies of thiazoline and thiazolidine-containing natural products - 1. Phosphorus pentachloride-mediated thiazoline construction reaction
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Phosphorus pentachloride effectively mediates the cyclization of N- acylcysteamine derivatives giving rise to thiazoline rings. Using this method, sterically hindered thiazoline analogs could be constructed and thus segment A (the left half) of micacocidin, a unique antimycoplasma antibiotic, was synthesized efficiently.
- Ino, Akira,Murabayashi, Akira
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p. 10271 - 10282
(2007/10/03)
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- SYNTHESES OF ANACARDIC ACIDS AND GINKGOIC ACID
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Syntheses of two anacardic acids , inhibitors of prostaglandin synthetase and of the growth of certain insects, and ginkgoic acid via directive metallation is reported.
- Yamagiwa, Yoshiro,Ohashi, Kinji,Sakamoto, Yoshitaka,Hirakawa, Shinji,Kamikawa, Tadao,Kubo, Isao
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p. 3387 - 3394
(2007/10/02)
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- Prostaglandin Synthetase Inhibitors from the African Medicinal Plant
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Two prostaglandin synthetase inhibitory anacardic acids were isolated from O. mucronata.The structures of these inhibitors were established by spectroscopic means.Efficient syntheses of these two via directive metallation were reported.
- Kubo, Isao,Kim, Mujo,Komatsu, Sakae,Yamagiwa, Yoshiro,Ohashi, Kinji,et al.
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p. 1101 - 1104
(2007/10/02)
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- Synthesis of 1,2,3,4-Tetrahydroisoquinolines
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Several aspects of 1,2,3,4-tetrahydroisoquinoline synthesis have been examined.An improved synthesis of 2-(m-methoxyphenyl)ethylamine (4) is reported. m-Anisaldehyde (5) was treated with potassium cyanide and ethyl chloroformate to yield O-(ethoxycarbonyl)-3-methoxymandelonitrile (7).Hydrogenation afforded 2-(m-methoxyphenyl)ethylamine (4) in 87percent yield overall.Some observations have been made regarding the reduction of 3,4-dihydroisoquinolines derived from the Bischler-Napieralski reaction.Amides 3a and 3c were cyclized with phosphorus oxychloride, followed by reduction to the corresponding tetrahydroisoquinolines 1a and 1c.It was shown that 1a and 1c were contaminated with 4percent of 2a and 3percent of 2c, respectively.Both 2a and 2c were independently synthesized by routes with general applicability to 8-alkoxy-1,2,3,4-tetrahydroisoquinolines.
- Kashdan, David S.,Schwartz, John A.,Rapoport, Henry
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p. 2638 - 2643
(2007/10/02)
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