| 1. |
- Grigorjeva, Liene, et al.
(författare)
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Semisynthesis of Libiguin A and Its Analogues by Trans-Lactonization of Phragmalin
- 2014
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 79:9, s. 4148-4153
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Tidskriftsartikel (refereegranskat)abstract
- Libiguins are limonoids with highly potent sexual activity enhancing effects, originally isolated from the Madagascarian Meliaceae species Neobeguea mahafalensis, where they exist in only minute quantities. Their low natural abundance has hampered mapping of their biological effects. Here we describe an approach to the semisynthesis of libiguin A and its close analogues 1-3 starting from phragmalin, which is a limonoid present in high amounts in a commercially cultivated Meliaceae species, Chukrasia tabularis, allowing the preparation of libiguins in appreciable quantities.
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| 2. |
- Mutulis, Felikss, et al.
(författare)
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N-alkylated dipeptide amides and related structures as imitations of the melanocortins' active core
- 2005
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 26:10, s. 1997-2016
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-three low molecular mass structures combining both peptide and peptoid features were prepared and tested on human melanocortin receptors MC1,3-5R. Most of them displayed low micromolar activity with preference for diamines, guanidino and 2-naphthyl derivatives compared to monoacetylated, amino and 3-indolyl counterparts. Some contained L- or D-histidine residues, but the change did not influence affinity. QSAR modelling yielded excellent models for the MC3-5 receptors explaining R2Y=0.89-0.91 and predicting Q2=0.77-0.80 of the affinity variations. One compound displayed MC1R selectivity (13-fold and more). An NMR study of showed that it exists as a mixture of four rotamers at its tertiary amide bonds. Comparisons with earlier data for melanocortin core tetrapeptide analogues indicate that the novel peptide-peptoids interact with the melanocortin receptors in a different way.
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| 3. |
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| 4. |
- Mutulis, Felikss, et al.
(författare)
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Oligomerization of indole derivatives with incorporation of thiols
- 2008
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 13:8, s. 1846-63
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Tidskriftsartikel (refereegranskat)abstract
- Two molecules of indole derivative, e.g. indole-5-carboxylic acid, reacted with one molecule of thiol, e.g. 1,2-ethanedithiol, in the presence of trifluoroacetic acid to yield adducts such as 3-[2-(2-amino-5-carboxyphenyl)-1-(2-mercaptoethylthio)ethyl]-1Hindole-5-carboxylic acid. Parallel formation of dimers, such as 2,3-dihydro-1H,1'H-2,3'-biindole-5,5'-dicarboxylic acid and trimers, such as 3,3'-[2-(2-amino-5-carboxyphenyl) ethane-1,1-diyl]bis(1H-indole-5-carboxylic acid) of the indole derivatives was also observed. Reaction of a mixture of indole and indole-5-carboxylic acid with 2-phenylethanethiol proceeded in a regioselective way, affording 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H-indole-5-carboxylic acid. An additional product of this reaction was 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-2,3-dihydro-1H,1'H-2,3'-biindole-5'-carboxylic acid, which upon standing in DMSO-d6 solution gave 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H,1'H-2,3'-biindole-5'-carboxylic acid. Structures of all compounds were elucidated by NMR, and a mechanism for their formation was suggested.
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| 5. |
- Razafimahefa, Solofoniaina, et al.
(författare)
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Libiguins A and B : Novel Phragmalin Limonoids Isolated from Neobeguea mahafalensis Causing Profound Enhancement of Sexual Activity
- 2014
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Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 80:4, s. 306-314
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Tidskriftsartikel (refereegranskat)abstract
- In a screening programme directed towards the discovery of drugs that could enhance sexual activity, we found that a decoction of the root bark of Neobeguea mahafalensis displayed an extraordinarily high potency and remarkably long duration in augmenting sexual activity in male rodents. Bioassay-guided fractionation led to the isolation of two pharmacoactive constituents, which turned out to be novel 1,8,9-orthoacetate phragmalin limonoids that we named libiguins A and B, each with a C-16/30 -lactone ring. Chemical structures were established by the interpretation of their 1D and 2DNMR data. In vivo pharmacological tests showed that starting with a treatment from 0.004-0.4mg/kg/day for three consecutive days, over a 3-h sampling period, these limonoids induced a long-lasting augmentation of frequency and sustainment of mounting behaviour in male rodents, with an effect lasting for up to 11 days post-treatment. Libiguin A proved to be markedly more potent than libiguin B. This report is the first of limonoids having such an effect, and the findings could lead to novel therapies for the treatment of sexual dysfunction. Moreover, the results can serve as an opening to elucidate the central physiological control of mating behaviour, which is still not well mapped out.
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