Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi
Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compou...
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paper:paper_09680896_v23_n15_p4804_GarciaLinares2023-06-08T15:58:57Z Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi García Liñares, Guadalupe E. Baldessari, Alicia Bile acids Chagas disease Lipase-catalyzed Molecular modeling acetic acid derivative bile acid chenodeoxycholic acid chenodeoxycholic acid 3,7 diacetate deoxycholic acid ethyl chenodeoxycholate 3 acetate lithocholic acid nucleophile unclassified drug antiprotozoal agent bile acid fungal protein lipase B, Candida antarctica solvent triacylglycerol lipase alcoholysis Article controlled study enzyme active site enzyme mechanism enzyme substrate enzyme synthesis esterification growth inhibition hydrophilicity hydrophobicity IC50 molecular model nonhuman nucleophilicity protein acetylation reaction analysis solvent effect structure activity relation structure analysis temperature measurement Trypanosoma cruzi acetylation binding site biocatalysis biosynthesis chemistry drug effects enzyme specificity growth, development and aging metabolism molecular docking preclinical study protein tertiary structure stereoisomerism temperature Trypanosoma cruzi Protozoa Trypanosoma cruzi Acetylation Antiprotozoal Agents Bile Acids and Salts Binding Sites Biocatalysis Drug Evaluation, Preclinical Esterification Fungal Proteins Lipase Molecular Docking Simulation Protein Structure, Tertiary Solvents Stereoisomerism Substrate Specificity Temperature Trypanosoma cruzi Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Trypanosoma cruzi growth inhibitors, obtaining the best results with ethyl chenodeoxycholate 3-acetate and chenodeoxycholic acid 3,7-diacetate, which showed IC50: 8.6 and 22.8 μM, respectively. In addition, in order to shed light to bile acids behavior in enzymatic reactions, molecular modeling was applied to some derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to synthesize these bile acid derivatives with application as potential antiparasitic agents. © 2015 Elsevier Ltd. All rights reserved. Fil:García Liñares, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Baldessari, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v23_n15_p4804_GarciaLinares http://hdl.handle.net/20.500.12110/paper_09680896_v23_n15_p4804_GarciaLinares |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Bile acids Chagas disease Lipase-catalyzed Molecular modeling acetic acid derivative bile acid chenodeoxycholic acid chenodeoxycholic acid 3,7 diacetate deoxycholic acid ethyl chenodeoxycholate 3 acetate lithocholic acid nucleophile unclassified drug antiprotozoal agent bile acid fungal protein lipase B, Candida antarctica solvent triacylglycerol lipase alcoholysis Article controlled study enzyme active site enzyme mechanism enzyme substrate enzyme synthesis esterification growth inhibition hydrophilicity hydrophobicity IC50 molecular model nonhuman nucleophilicity protein acetylation reaction analysis solvent effect structure activity relation structure analysis temperature measurement Trypanosoma cruzi acetylation binding site biocatalysis biosynthesis chemistry drug effects enzyme specificity growth, development and aging metabolism molecular docking preclinical study protein tertiary structure stereoisomerism temperature Trypanosoma cruzi Protozoa Trypanosoma cruzi Acetylation Antiprotozoal Agents Bile Acids and Salts Binding Sites Biocatalysis Drug Evaluation, Preclinical Esterification Fungal Proteins Lipase Molecular Docking Simulation Protein Structure, Tertiary Solvents Stereoisomerism Substrate Specificity Temperature Trypanosoma cruzi |
| spellingShingle |
Bile acids Chagas disease Lipase-catalyzed Molecular modeling acetic acid derivative bile acid chenodeoxycholic acid chenodeoxycholic acid 3,7 diacetate deoxycholic acid ethyl chenodeoxycholate 3 acetate lithocholic acid nucleophile unclassified drug antiprotozoal agent bile acid fungal protein lipase B, Candida antarctica solvent triacylglycerol lipase alcoholysis Article controlled study enzyme active site enzyme mechanism enzyme substrate enzyme synthesis esterification growth inhibition hydrophilicity hydrophobicity IC50 molecular model nonhuman nucleophilicity protein acetylation reaction analysis solvent effect structure activity relation structure analysis temperature measurement Trypanosoma cruzi acetylation binding site biocatalysis biosynthesis chemistry drug effects enzyme specificity growth, development and aging metabolism molecular docking preclinical study protein tertiary structure stereoisomerism temperature Trypanosoma cruzi Protozoa Trypanosoma cruzi Acetylation Antiprotozoal Agents Bile Acids and Salts Binding Sites Biocatalysis Drug Evaluation, Preclinical Esterification Fungal Proteins Lipase Molecular Docking Simulation Protein Structure, Tertiary Solvents Stereoisomerism Substrate Specificity Temperature Trypanosoma cruzi García Liñares, Guadalupe E. Baldessari, Alicia Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
| topic_facet |
Bile acids Chagas disease Lipase-catalyzed Molecular modeling acetic acid derivative bile acid chenodeoxycholic acid chenodeoxycholic acid 3,7 diacetate deoxycholic acid ethyl chenodeoxycholate 3 acetate lithocholic acid nucleophile unclassified drug antiprotozoal agent bile acid fungal protein lipase B, Candida antarctica solvent triacylglycerol lipase alcoholysis Article controlled study enzyme active site enzyme mechanism enzyme substrate enzyme synthesis esterification growth inhibition hydrophilicity hydrophobicity IC50 molecular model nonhuman nucleophilicity protein acetylation reaction analysis solvent effect structure activity relation structure analysis temperature measurement Trypanosoma cruzi acetylation binding site biocatalysis biosynthesis chemistry drug effects enzyme specificity growth, development and aging metabolism molecular docking preclinical study protein tertiary structure stereoisomerism temperature Trypanosoma cruzi Protozoa Trypanosoma cruzi Acetylation Antiprotozoal Agents Bile Acids and Salts Binding Sites Biocatalysis Drug Evaluation, Preclinical Esterification Fungal Proteins Lipase Molecular Docking Simulation Protein Structure, Tertiary Solvents Stereoisomerism Substrate Specificity Temperature Trypanosoma cruzi |
| description |
Enzyme catalysis was applied to synthesize derivatives of three bile acids and their biological activity was evaluated as growth inhibitors of the protozoan Trypanosoma cruzi. Twelve mono-, diacetyl and ester derivatives of deoxycholic, chenodeoxycholic and lithocholic acid, seven of them new compounds, were obtained through lipase-catalyzed acetylation, esterification and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one-pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Trypanosoma cruzi growth inhibitors, obtaining the best results with ethyl chenodeoxycholate 3-acetate and chenodeoxycholic acid 3,7-diacetate, which showed IC50: 8.6 and 22.8 μM, respectively. In addition, in order to shed light to bile acids behavior in enzymatic reactions, molecular modeling was applied to some derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to synthesize these bile acid derivatives with application as potential antiparasitic agents. © 2015 Elsevier Ltd. All rights reserved. |
| author |
García Liñares, Guadalupe E. Baldessari, Alicia |
| author_facet |
García Liñares, Guadalupe E. Baldessari, Alicia |
| author_sort |
García Liñares, Guadalupe E. |
| title |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
| title_short |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
| title_full |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
| title_fullStr |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
| title_full_unstemmed |
Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi |
| title_sort |
enzymatic synthesis of bile acid derivatives and biological evaluation against trypanosoma cruzi |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v23_n15_p4804_GarciaLinares http://hdl.handle.net/20.500.12110/paper_09680896_v23_n15_p4804_GarciaLinares |
| work_keys_str_mv |
AT garcialinaresguadalupee enzymaticsynthesisofbileacidderivativesandbiologicalevaluationagainsttrypanosomacruzi AT baldessarialicia enzymaticsynthesisofbileacidderivativesandbiologicalevaluationagainsttrypanosomacruzi |
| _version_ |
1768544460743901184 |