Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors
Objective(s): 15-Lipoxygenases are one of the iron-containing proteins capable of performing peroxidation of unsaturated fatty acids in animals and plants. The critical role of enzymes in the formation of inflammations, sensitivities, and some cancers has been demonstrated in mammals. The importance...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2018-07-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | http://ijbms.mums.ac.ir/article_10763_b671f07c65669017ad8668ab9b1956a5.pdf |
| _version_ | 1818206695924432896 |
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| author | Hamid Sadeghian Seyed Mohammad Seyedi Zeinab Jafari |
| author_facet | Hamid Sadeghian Seyed Mohammad Seyedi Zeinab Jafari |
| author_sort | Hamid Sadeghian |
| collection | DOAJ |
| description | Objective(s): 15-Lipoxygenases are one of the iron-containing proteins capable of performing peroxidation of unsaturated fatty acids in animals and plants. The critical role of enzymes in the formation of inflammations, sensitivities, and some cancers has been demonstrated in mammals. The importance of enzymes has led to the development of mechanistic studies, product analysis, and synthesis of inhibitors. Materials and Methods: The inhibitory activity of all synthetic compounds against SLO (soybean 15-lipoxygenase: L1; EC 1,13,11,12) was determined using the peroxide formation method. In this method, the basis of evaluation of lipoxygenase activity is measuring the concentration of fatty acid peroxide. All measurements were compared with 4-methyl-2-(4-methylpiperazinyl)pyrimido[4,5-b]benzothiazine (4-MMPB) as one of the known lipoxygenase inhibitors. The radical scavenging ability of all synthetic compounds using stable free radicals (DPPH: 2,2-diphenyl-1-picrylhydrazyl) was measured for further investigation.Results: In this study, a series of esters from phenolic acids with terpenoid alcohols was synthesized and their inhibitory potency against soybean 15-lipoxygenase and their free radical scavenging properties were determined. Among the synthetic compounds, adamantyl protocatetuate 2j and bornyl protocatetuate 2o showed the most potent inhibitory activity with IC50 values of 0.95 and 0.78 μm, respectively.Conclusion: By changing the alcohol and acyl portions of stylosin, it was found that electronic properties play main role in lipoxygenase inhibition potency in contrast with steric features. Insertion of more reductive phenolic moiety such as catechuate and gallate lead to more lipoxygenase inhibition potency of the esters as observed in their radical scavenging activity. |
| first_indexed | 2024-12-12T04:17:07Z |
| format | Article |
| id | doaj.art-5f62d6e6a89a48f78a40ea07b9bf4066 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-12T04:17:07Z |
| publishDate | 2018-07-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-5f62d6e6a89a48f78a40ea07b9bf40662022-12-22T00:38:26ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742018-07-0121773874410.22038/ijbms.2018.27910.679410763Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitorsHamid Sadeghian0Seyed Mohammad Seyedi1Zeinab Jafari2Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran|Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, IranDepartment of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, IranObjective(s): 15-Lipoxygenases are one of the iron-containing proteins capable of performing peroxidation of unsaturated fatty acids in animals and plants. The critical role of enzymes in the formation of inflammations, sensitivities, and some cancers has been demonstrated in mammals. The importance of enzymes has led to the development of mechanistic studies, product analysis, and synthesis of inhibitors. Materials and Methods: The inhibitory activity of all synthetic compounds against SLO (soybean 15-lipoxygenase: L1; EC 1,13,11,12) was determined using the peroxide formation method. In this method, the basis of evaluation of lipoxygenase activity is measuring the concentration of fatty acid peroxide. All measurements were compared with 4-methyl-2-(4-methylpiperazinyl)pyrimido[4,5-b]benzothiazine (4-MMPB) as one of the known lipoxygenase inhibitors. The radical scavenging ability of all synthetic compounds using stable free radicals (DPPH: 2,2-diphenyl-1-picrylhydrazyl) was measured for further investigation.Results: In this study, a series of esters from phenolic acids with terpenoid alcohols was synthesized and their inhibitory potency against soybean 15-lipoxygenase and their free radical scavenging properties were determined. Among the synthetic compounds, adamantyl protocatetuate 2j and bornyl protocatetuate 2o showed the most potent inhibitory activity with IC50 values of 0.95 and 0.78 μm, respectively.Conclusion: By changing the alcohol and acyl portions of stylosin, it was found that electronic properties play main role in lipoxygenase inhibition potency in contrast with steric features. Insertion of more reductive phenolic moiety such as catechuate and gallate lead to more lipoxygenase inhibition potency of the esters as observed in their radical scavenging activity.http://ijbms.mums.ac.ir/article_10763_b671f07c65669017ad8668ab9b1956a5.pdfInhibitorsPhenolic acidRadical scavengingTerpenoids15-lipoxygenase |
| spellingShingle | Hamid Sadeghian Seyed Mohammad Seyedi Zeinab Jafari Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors Iranian Journal of Basic Medical Sciences Inhibitors Phenolic acid Radical scavenging Terpenoids 15-lipoxygenase |
| title | Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors |
| title_full | Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors |
| title_fullStr | Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors |
| title_full_unstemmed | Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors |
| title_short | Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors |
| title_sort | design and synthesis of new esters of terpenoid alcohols as 15 lipoxygenase inhibitors |
| topic | Inhibitors Phenolic acid Radical scavenging Terpenoids 15-lipoxygenase |
| url | http://ijbms.mums.ac.ir/article_10763_b671f07c65669017ad8668ab9b1956a5.pdf |
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