Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives

Faridah Faridah; Dian Ratih Laksmıtawatı; Partomuan Simanjuntak; Shirly Kumala; Intan Permata Sari; Eko Mugiyanto

doi:10.12991/jrespharm.1797754

Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives

Abstract

Natural compounds with anti-obesity properties offer promising therapeutic alternatives to synthetic drugs, given their potential for fewer side effects and broader accessibility. Among these compounds, chlorogenic acid (CGA), a polyphenolic compound found in coffee, fruits, and vegetables, has demonstrated significant benefits in weight management and metabolic regulation. This study explores the efficacy of penta-acetyl-chlorogenic acid, an acetylated derivative of chlorogenic acid, as a novel anti-obesity agent. Penta-acetyl-chlorogenic acid (PACA) was synthesized through the Hoffmann method and evaluated for its effects through both in vitro and in silico approaches. The compound demonstrated potent inhibitory effects in vitro via lipase inhibition, with an IC₅₀ of 45.63 μg/ml. The results indicate that acetylation enhances the bioactivity of chlorogenic acid, making PACA a promising candidate for obesity control. Furthermore, in silico docking studies were conducted targeting key proteins associated with obesity, lipase, with binding affinities of -99.50, kcal/mol. Docking results showed strong binding affinities of PACA to these targets, supporting its potential role in modulating lipid metabolism. In summary, this derivative represents a new perspective on the therapeutic potential of chlorogenic acid and its analogs. Further studies are warranted to assess the in vivo relevance of PACA in obesity therapy.

Keywords

References

[1] Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6-10. http://dx.doi.org/10.1016/j.metabol.2018.09.005.
[2] Pataky Z, Bobbioni-Harsch E, Golay A. Obesity: a complex growing challenge. Exp Clin Endocrinol Diabetes. 2010;118(7):427-433. http://dx.doi.org/10.1055/s-0029-1233448.
[3] Haththotuwa RN, Wijeyaratne CN, Senarath U. Worldwide epidemic of obesity. In: Obesity and Obstetrics, Elsevier, 2020, pp. 3–8. http://dx.doi.org/10.1016/B978-0-12-817921-5.00001-1.
[4] Hecker J, Freijer K, Hiligsmann M, Evers SMAA. Burden of disease study of overweight and obesity; the societal impact in terms of cost-of-illness and health-related quality of life. BMC Public Health. 2022;22(1):46. http://dx.doi.org/10.1186/s12889-021-12449-2.
[5] Tak YJ, Lee SY. Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review. World J Mens Health. 2021;39(2):208-221. http://dx.doi.org/10.5534/wjmh.200010.
[6] Tampubolon J, Ginting A, Nainggolan HL, Tarigan JR. Indonesian Coffee Development Path: Production and International Trade. Asian J Agric Extens Econ Sociol. 2023; 41(12): 316–328. http://dx.doi.org/10.9734/ajaees/2023/v41i122335.
[7] Muchtaridi M, Lestari D, Khairul Ikram NK, Gazzali AM, Hariono M, Wahab HA. Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound. Molecules. 2021;26(11):3402. http://dx.doi.org/10.3390/molecules26113402.
[8] Clifford MN, Jaganath IB, Ludwig IA, Crozier A. Chlorogenic acids and the acyl-quinic acids: discovery, biosynthesis, bioavailability and bioactivity. Nat Prod Rep. 2017;34(12):1391-1421. http://dx.doi.org/10.1039/C7NP00030H.

[9] Rojas-González A, Figueroa-Hernández CY, González-Rios O, Suárez-Quiroz ML, González-Amaro RM, Hernández-Estrada ZJ, Rayas-Duarte P. Coffee Chlorogenic Acids Incorporation for Bioactivity Enhancement of Foods: A Review. Molecules. 2022;27(11):3400. http://dx.doi.org/10.3390/molecules27113400.
[10] Bhandarkar NS, Brown L, Panchal SK. Chlorogenic acid attenuates high-carbohydrate, high-fat diet-induced cardiovascular, liver, and metabolic changes in rats. Nutr Res. 2019;62:78-88. http://dx.doi.org/10.1016/j.nutres.2018.11.002.
[11] Sondheimer E. Chlorogenic acids and related depsides. In: The Botanical Review. 1964; 30(4): 667–712. http://dx.doi.org/10.1007/BF02858654.
[12] Clifford MN, Kerimi A, Williamson G. Bioavailability and metabolism of chlorogenic acids (acyl-quinic acids) in humans. Compr Rev Food Sci Food Saf. 2020;19(4):1299-1352. http://dx.doi.org/10.1111/1541-4337.12518.
[13] Zhu S, Li Y, Li Z, Ma C, Lou Z, Yokoyama W, Wang H. Lipase-catalyzed synthesis of acetylated EGCG and antioxidant properties of the acetylated derivatives. Food Res Int. 2014; 56: 279–286. http://dx.doi.org/10.1016/j.foodres.2013.10.026.
[14] Perlovich GL, Bauer-Brandl A. The melting process of acetylsalicylic acid single crystals. J Therm Anal Calorim. 2001; 63(3): 653–661. http://dx.doi.org/10.1023/A:1010119532614.
[15] Isbell TA, Edgcomb MR, Lowery BA. Physical properties of estolides and their ester derivatives. Ind Crops Prod. 2001; 13(1): 11–20. https://doi.org/10.1016/S0926-6690(00)00045-5
[16] Floris B, Galloni P, Conte V, Sabuzi F. Tailored Functionalization of Natural Phenols to Improve Biological Activity. Biomolecules. 2021;11(9):1325. http://dx.doi.org/10.3390/biom11091325.
[17] Salhi A, Carriere F, Grundy MML, Aloulou A. Enzymes Involved in Lipid Digestion. In: Bioaccessibility and Digestibility of Lipids from Food. Cham: Springer International Publishing, 2021, pp. 3–28. http://dx.doi.org/10.1007/978-3-030-56909-9_1.
[18] Faridah F, Mumpuni E, Purnomo H, Laksmitawati DR, Simanjuntak P. Study of The Anti-Obesity Potential of Chlorogenic Acid Through Molecular Docking. J Soc Res.2024; 3(2). http://dx.doi.org/10.55324/josr.v3i2.1910.
[19] Ambigaipalan P, Oh WY, Shahidi F. Epigallocatechin (EGC) esters as potential sources of antioxidants. Food Chem. 2020;309:125609. http://dx.doi.org/10.1016/j.foodchem.2019.125609.
[20] van de Waterbeemd H, Karajiannis H, El Tayar N. Lipophilicity of amino acids. Amino Acids. 1994 ;7(2):129-145. https://doi.org/10.1007/bf00814156.
[21] Fragopoulou E, Nomikos T, Karantonis HC, Apostolakis C, Pliakis E, Samiotaki M, Panayotou G, Antonopoulou S. Biological activity of acetylated phenolic compounds. J Agric Food Chem. 2007;55(1):80-89. http://dx.doi.org/10.1021/jf0627221.
[22] Weber WW. acetylation of drugs. In: Metabolic Conjugation and Metabolic Hydrolysis, Elsevier, 1973, pp. 249–296. http://dx.doi.org/10.1016/B978-0-12-257603-4.50012-4.
[23] Su X, Wellen KE, Rabinowitz JD. Metabolic control of methylation and acetylation. Curr Opin Chem Biol. 2016;30:52-60. http://dx.doi.org/10.1016/j.cbpa.2015.10.030.
[24] Zhuang Y, Quan W, Wang X, Cheng Y, Jiao Y. Comprehensive Review of EGCG Modification: Esterification Methods and Their Impacts on Biological Activities. Foods. 2024;13(8):1232. http://dx.doi.org/10.3390/foods13081232.
[25] Liu TT, Liu XT, Chen QX, Shi Y. Lipase Inhibitors for Obesity: A Review. Biomed Pharmacother. 2020;128:110314. http://dx.doi.org/10.1016/j.biopha.2020.110314.
[26] Hevener KE, Zhao W, Ball DM, Babaoglu K, Qi J, White SW, Lee RE. Validation of molecular docking programs for virtual screening against dihydropteroate synthase. J Chem Inf Model. 2009;49(2):444-460. http://dx.doi.org/10.1021/ci800293n.
[27] Otache MA, Duru RU, Achugasim O, Abayeh OJ. Advances in the Modification of Starch via Esterification for Enhanced Properties. J Polym Environ. 2021; 29(5): 1365–1379. http://dx.doi.org/10.1007/s10924-020-02006-0.
[28] Shi J, Zhang L, Cheng Z. Design of Water-Tolerant Solid Acids: A Trade-Off Between Hydrophobicity and Acid Strength and their Catalytic Performance in Esterification. Catalysis Surveys from Asia. 202125(3): 279–300. http://dx.doi.org/10.1007/s10563-021-09334-8.
[29] Cui H, López M, Rahmouni K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol. 2017 ;13(6):338-351. http://dx.doi.org/10.1038/nrendo.2016.222.
[30] Ellrichmann M. Orlistat and the Influence on Appetite Signals. In: Handbook of Behavior, Food and Nutrition, New York, NY: Springer New York, 2011, pp. 1331–1350. http://dx.doi.org/10.1007/978-0-387-92271-3_86.
[31] Uehira Y, Ueno H, Miyamoto J, Kimura I, Ishizawa Y, Iijima H, Muroga S, Fujita T, Sakai S, Samukawa Y, Tanaka Y, Murayama S, Sakoda H, Nakazato M. Impact of the lipase inhibitor orlistat on the human gut microbiota. Obes Res Clin Pract. 2023;17(5):411-420. http://dx.doi.org/10.1016/j.orcp.2023.08.005.
[32] Drayer DE, Reidenberg MM. Clinical consequences of polymorphic acetylation of basic drugs. Clin Pharmacol Ther. 1977;22(3):251-258. http://dx.doi.org/10.1002/cpt1977223251.
[33] Patrono C. Aspirin: 1A @ 125. Eur Heart J. 2022;43(34):3194-3195. http://dx.doi.org/10.1093/eurheartj/ehac416.
[34] Sneader W. The discovery of aspirin: a reappraisal. BMJ. 2000;321(7276):1591-1594. http://dx.doi.org/10.1136/bmj.321.7276.1591.
[35] Yalkowsky SH, Alantary D. Estimation of Melting Points of Organics. J Pharm Sci. 2018;107(5):1211-1227. http://dx.doi.org/10.1016/j.xphs.2017.12.013.
[36] Lin SF, Chiou CM, Yeh CM, Tsai YC. Purification and partial characterization of an alkaline lipase from Pseudomonas pseudoalcaligenes F-111. Appl Environ Microbiol. 1996;62(3):1093-1095. http://dx.doi.org/10.1128/aem.62.3.1093-1095.1996.
[37] Exner T, Korb O, ten Brink T. New and improved features of the docking software PLANTS. Chem Cent J. 2009; 3(S1): P16. http://dx.doi.org/10.1186/1752-153X-3-S1-P16.
[38] Mugiyanto E, Fajriyah NN. Indonesia herbal medicine and its active compounds for anti-diabetic treatment: A systematic mini review. Moroccan J Chem. 2023; 11(04): 948–964. https://doi.org/10.48317/IMIST.PRSM/morjchem-v11i04.40481.

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Faridah Faridah
0009-0008-7083-2722
Indonesia

Dian Ratih Laksmıtawatı ^*
0000-0001-8484-0290
Indonesia

Partomuan Simanjuntak
0000-0002-8501-908X
Indonesia

Shirly Kumala
Indonesia

Intan Permata Sari This is me
0000-0001-6558-7736
Indonesia

Eko Mugiyanto This is me
0000-0001-9777-4800
Indonesia

Publication Date

November 2, 2025

Submission Date

December 22, 2024

Acceptance Date

February 15, 2025

Published in Issue

Year 2025 Volume: 29 Number: 6

DOI

https://doi.org/10.12991/jrespharm.1797754

IZ

https://izlik.org/JA47FG86SR

Cite

RIS / Bibtex

APA

Faridah, F., Laksmıtawatı, D. R., Simanjuntak, P., Kumala, S., Sari, I. P., & Mugiyanto, E. (2025). Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives. Journal of Research in Pharmacy, 29(6), 2267-2277. https://doi.org/10.12991/jrespharm.1797754

AMA

1.Faridah F, Laksmıtawatı DR, Simanjuntak P, Kumala S, Sari IP, Mugiyanto E. Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives. J. Res. Pharm. 2025;29(6):2267-2277. doi:10.12991/jrespharm.1797754

Chicago

Faridah, Faridah, Dian Ratih Laksmıtawatı, Partomuan Simanjuntak, Shirly Kumala, Intan Permata Sari, and Eko Mugiyanto. 2025. “Penta-Acetylchlorogenic Acıd for Obesity Control: A New Perspective on Chlorogenic Acid Derivatives”. Journal of Research in Pharmacy 29 (6): 2267-77. https://doi.org/10.12991/jrespharm.1797754.

EndNote

Faridah F, Laksmıtawatı DR, Simanjuntak P, Kumala S, Sari IP, Mugiyanto E (November 1, 2025) Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives. Journal of Research in Pharmacy 29 6 2267–2277.

IEEE

[1]F. Faridah, D. R. Laksmıtawatı, P. Simanjuntak, S. Kumala, I. P. Sari, and E. Mugiyanto, “Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives”, J. Res. Pharm., vol. 29, no. 6, pp. 2267–2277, Nov. 2025, doi: 10.12991/jrespharm.1797754.

ISNAD

Faridah, Faridah - Laksmıtawatı, Dian Ratih - Simanjuntak, Partomuan - Kumala, Shirly - Sari, Intan Permata - Mugiyanto, Eko. “Penta-Acetylchlorogenic Acıd for Obesity Control: A New Perspective on Chlorogenic Acid Derivatives”. Journal of Research in Pharmacy 29/6 (November 1, 2025): 2267-2277. https://doi.org/10.12991/jrespharm.1797754.

JAMA

1.Faridah F, Laksmıtawatı DR, Simanjuntak P, Kumala S, Sari IP, Mugiyanto E. Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives. J. Res. Pharm. 2025;29:2267–2277.

MLA

Faridah, Faridah, et al. “Penta-Acetylchlorogenic Acıd for Obesity Control: A New Perspective on Chlorogenic Acid Derivatives”. Journal of Research in Pharmacy, vol. 29, no. 6, Nov. 2025, pp. 2267-7, doi:10.12991/jrespharm.1797754.

Vancouver

1.Faridah Faridah, Dian Ratih Laksmıtawatı, Partomuan Simanjuntak, Shirly Kumala, Intan Permata Sari, Eko Mugiyanto. Penta-acetylchlorogenic acıd for obesity control: A new perspective on chlorogenic acid derivatives. J. Res. Pharm. 2025 Nov. 1;29(6):2267-7. doi:10.12991/jrespharm.1797754