- Combination anti-HIV therapy with the self-assemblies of an asymmetric bolaamphiphilic zidovudine/didanosine prodrug
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Combination anti-HIV therapy is important for AIDS treatment. A bolaamphiphilic prodrug, zidovudine-phosphoryl-deoxycholyl didanosine (ZPDD), was synthesized, combining zidovudine (AZT) and didanosine (ddI) in one molecule. As one lipid derivative of nucleosides, ZPDD showed special solubility with free soluble in chloroform and tetrahydrofuran but was slightly soluble in cyclohexane. The amphiphilicity of ZPDD was shown according to the monolayers at the air-water interface. ZPDD self-assembled to the spherical vesicles in water with 174 nm in size and -31.3 mV of zeta potential. The stability of assemblies depended on pH because the phosphoryl zidovudine group could release hydrogen ions. ZPDD was rapidly degraded to AZT in the plasma and tissues of mice. ZPDD self-assemblies had high anti-HIV activity in vitro with the half effective concentration (EC50) of 5 nM. ZPDD self-assemblies may be targeting macrophages since ZPDD was found in macrophage-rich tissues in vivo and rapidly released AZT in the targeted tissues after intravenous administration to mice. The bioavailability of ZPDD was 90.5% and 30.8% for the intraperitoneal and oral administrations compared with the venous route. The self-assemblies of bolaamphiphilic prodrugs could simultaneously deliver two types of drugs to targeted tissues and would become a promising nanomedicine.
- Jin, Yiguang,Xin, Rui,Tong, Li,Du, Lina,Li, Miao
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- Study on the bile salt from megamouth shark. I. The structures of a new bile alcohol, 7-deoxyscymnol, and its new sodium sulfates
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New sodium bile alcohol sulfates were obtained from the bile of megamouth shark by chromatography on silica gel and Sephadex LH-20, together with two sodium scymnol sulfates, (24R,25S)- and (24R,25R)- (+)3α,7α,12α,24,26-pentahydroxy-5β-cholestan-27-yl sodium sulfate (2 and 3). On hydrolysis in pyridine-dioxane, the new salts afforded a new bile alcohol (1), whose structure was determined to be (24R)-5β-cholestane- 3α,12α,24,26,27-pentol, based on chemical and spectral data. On the basis of the physicochemical data, the new salts were established as (24R,25S)- and (24R,25R)-(+)-3α,12α,24,26-tetrahydroxy-5β-cholestan-27-yl sodium sulfate.
- Ishida, Hitoshi,Miyamoto, Hidekazu,Kajino, Takako,Nakayasu, Hidetoshi,Nukaya, Haruo,Tsuji, Kuniro
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- Regioselective microbial oxidation of bile acids
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High regioselectivity in the microbial oxidation of C7, C3 and C12 hydroxyl groups of cholic, chenodeoxycholic, deoxycholic and hyocholic acids 1-4 is reported. The tested microrganisms have been isolated from 50 environmental samples withdrawed from an industry that extracts and purify bile acids.
- Fantin, Giancarlo,Ferrarini, Sabina,Medici, Alessandro,Pedrini, Paola,Poli, Silvia
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- Short synthesis of orthogonally protected 3α,12α-diamino- 5β-cholan-24-oic acid, a dipodal steroid scaffold for combinatorial chemistry
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A short, practical, multigram-scale synthesis of C3α-NHAlloc, C12α-NHBoc-diamino-5β-cholan-24-oic acid 2 was developed, applying a new, straightforward synthetic strategy. Key features are the conservation of the carboxyl moiety at C24 during oxime reduction, the late differentiation between the C3 and C12 amino groups and the gradual separation of diastereomers during the synthesis. This orthogonally protected diarnino steroid derivative can be used as starting point for the generation of steroid based dipodal peptide and non-peptide combinatorial libraries. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Verzele, Dieter,Madder, Annemieke
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- Biotransformations of Bile Acids with Bacteria from Cayambe Slaughterhouse (Ecuador): Synthesis of Bendigoles
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The biotransformations of cholic acid (1a), deoxycholic acid (1b), and hyodeoxycholic acid (1c) to bendigoles and other metabolites with bacteria isolated from the rural slaughterhouse of Cayambe (Pichincha Province, Ecuador) were reported. The more active strains were characterized, and belong to the genera Pseudomonas and Rhodococcus. Various biotransformation products were obtained depending on bacteria and substrates. Cholic acid (1a) afforded the 3-oxo and 3-oxo-4-ene derivatives 2a and 3a (45% and 45%, resp.) with P.?mendocina ECS10, 3,12-dioxo-4-ene derivative 4a (60%) with Rh.?erythropolis ECS25, and 9,10-secosteroid 6 (15%) with Rh.?erythropolis ECS12. Bendigole F (5a) was obtained in 20% with P.?fragi ECS22. Deoxycholic acid (1b) gave 3-oxo derivative 2b with P.?prosekii ECS1 and Rh.?erythropolis ECS25 (20% and 61%, resp.), while 3-oxo-4-ene derivative 3b was obtained with P.?prosekii ECS1 and P.?mendocina ECS10 (22% and 95%, resp.). Moreover, P.?fragi ECS9 afforded bendigole A (8b; 80%). Finally, P.?mendocina ECS10 biotransformed hyodeoxycholic acid (1c) to 3-oxo derivative 2c (50%) and Rh.?erythropolis ECS12 to 6α-hydroxy-3-oxo-23,24-dinor-5β-cholan-22-oic acid (9c, 66%). Bendigole G (5c; 13%) with P.?prosekii ECS1 and bendigole H?(8c) with P.?prosekii ECS1 and Rh.?erythropolis ECS12 (20% and 16%, resp.) were obtained.
- Costa, Stefania,Maldonado Rodriguez, Maria Elena,Rugiero, Irene,De Bastiani, Morena,Medici, Alessandro,Tamburini, Elena,Pedrini, Paola
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p. 969 - 975
(2016/09/09)
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- Synthesis and evaluation of some 17-acetamidoandrostane and N,N-dimethyl-7-deoxycholic amide derivatives as cytotoxic agents: Structure/activity studies
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Using pregnenolone and 7-deoxycholic acid as starting materials, some 17-acetamidoandrostane and N,N-dimethyl-7-deoxycholic amide derivatives were synthesized. The cytotoxicity of the synthesized compounds was tested in vitro against two tumor cell lines: SGC 7901 (human gastric carcinoma) and Bel 7404 (human liver carcinoma). The result showed that the blockage of the interaction of the amide group with outside groups might cause a decrease of the cytotoxicity, and an O-benzyloximino group at the 3-position of N,N-dimethyl-7-deoxycholic amide could enhance the cytotoxic activity of the compound. The information obtained from the studies provides the structure-activity relationship for these compounds and may be useful for the design of novel chemotherapeutic drugs.
- Huang, Yanmin,Cui, Jianguo,Jia, Linyi,Gan, Chunfang,Song, Huacan,Zeng, Chun,Zhou, Aimin
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p. 7436 - 7447
(2013/08/23)
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- Improved enantioselectivity in the epoxidation of cinnamic acid derivatives with dioxiranes from keto bile acids
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The asymmetric epoxidation of substituted cinnamic acids has been obtained in the presence of different keto bile acid derivatives as optically active carbonyl inducers and Oxone as oxygen source. Predominant or almost exclusive formation of both enantiomeric epoxides is obtained (ee up to 95%) depending on the specific substitution at carbons C(7) and C(12) of the bile acid.
- Bortolini, Olga,Fantin, Giancarlo,Fogagnolo, Marco,Forlani, Roberto,Maietti, Silvia,Pedrini, Paola
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p. 5802 - 5806
(2007/10/03)
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