Structure-Activity Relationship Study on the Ethyl  p -Methoxycinnamate as an Anti-Inflammatory Agent

Ismiarni Komala; Supandi Supandi; Nurhasni Nurhasni; Ofa Suzanti Betha; Eka Putri; Syarifatul Mufidah; Muhammad Fikry Awaludin; Mida Fahmi; Muhammad Reza; Nurkhayati Putri Indriyani

doi:10.22146/ijc.26162

Structure-Activity Relationship Study on the Ethyl p-Methoxycinnamate as an Anti-Inflammatory Agent

https://doi.org/10.22146/ijc.26162

Ismiarni Komala^(1*), Supandi Supandi⁽²⁾, Nurhasni Nurhasni⁽³⁾, Ofa Suzanti Betha⁽⁴⁾, Eka Putri⁽⁵⁾, Syarifatul Mufidah⁽⁶⁾, Muhammad Fikry Awaludin⁽⁷⁾, Mida Fahmi⁽⁸⁾, Muhammad Reza⁽⁹⁾, Nurkhayati Putri Indriyani⁽¹⁰⁾

(1) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(2) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(3) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(4) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(5) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(6) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(7) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(8) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(9) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(10) Department of Pharmacy, Faculty of Medicine and Health Sciences. Syarif Hidayatullah State Islamic University
(*) Corresponding Author

Abstract

Ethyl p-methoxycinnamate (EPMC) (1) has been isolated as a major compound from the rhizome of Kaempferia galanga together with the other compound ethyl cinnamate (2). As reported in the literature, EPMC (1) exhibited a significant in vitro and in vivo anti-inflammatory activity. In this research, we investigated the anti-inflammatory activity of compounds 1 and 2 by using anti-denaturation of heat bovine serum albumin (BSA) method. In order to analyze active sites that are responsible for the anti-inflammatory activity, therefore, it is necessary to conduct structural modification of EPMC (1). The structural modification was performed through re-esterification reaction by using conventional and assistance of the unmodified microwave oven. Evaluation of the results of the bioassay indicated that the ester and methoxy functional groups of EPMC (1) play an important role for the anti-inflammatory activity.

Keywords

Ethyl p-methoxycinnamate; anti-inflammatory; anti-denaturation; microwave oven assisted reaction; re-esterification

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References

[1] Umar, M.I., Asmawi, M.Z., Sadikun, A., Atangwho, I.J., Yam, M.F., Altaf, R., and Ahmed, A., 2012, Bioactivity-guided isolation of ethyl-p-methoxycinnamate, an anti-inflammatory constituent, from Kaempferia galanga L. extracts, Molecules, 17 (7), 8720–8734.

[2] Liu, X.C., Liang, Y., Shi, W.P., Liu, Q.Z., Zhou, L., and Liu, Z.L., 2014, Repellent and insecticidal effects of the essential oil of Kaempferia galanga rhizomes to Liposcelis bostrychophila (Psocoptera: Liposcelidae), J. Econ. Entomol.,107 (4), 1706–1712.

[3] Lakshmanan, D., Werngren, J., Jose, L., Suja, K.P., Nair, M.S., Varma, R.L., Mundayoor, S., Hoffner, S., and Kumar, R.A., 2011, Ethyl p-methoxycinnamate isolated from a traditional anti-tuberculosis medicinal herb inhibits drug-resistant strains of Mycobacterium tuberculosisin vitro, Fitoterapia, 82 (5), 757–761.

[4] Ali, M.S., Dash, P.R., and Nasrin, M., 2015, Study of sedative activity of different extracts of Kaempferia galanga in Swiss albino mice, BMC Complement. Altern. Med., 15, 158.

[5] He, Z.H., Yue, G.G., Lau, C.B., Ge, W., and But, P.P., 2012, Antiangiogenic effects and mechanisms of trans-ethyl p-methoxycinnamate from Kaempferia galanga L., J. Agric. Food Chem., 60 (45), 11309–11317.

[6] Umar, M.I., Asmawi, M.Z., Sadikun, A., Majid, A.M.S.A., Al-Suede, F.S.R., Hassan, L.E.A., Altaf, R., and Ahamed, M.B.K., 2014, Ethyl-p-methoxycinnamate isolated from Kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions, Clinics, 69 (2), 134–144.

[7] Ko, H.J., Kim, H.J., Kim, S.Y., Yun, H.Y., Baek, K.J., Kwon, N.S., Whang, W.K., Choi, H.R., Park, K.C., and Kim, D.S., 2014, Hypopigmentary effects of ethyl p-methoxycinnamate isolated from Kaempferia galanga, Phytother. Res., 28 (2), 274–279.

[8] Suzana, Irawati, N., and Budiati, T., 2011, Synthesis octyl p- methoxycinnamate as sunblock by transesterification reaction with the starting material ethyl p-methoxycinnamate, Indones. J. Cancer Chemoprevention, 2, 217–221.

[9] Ekowati, J., Tejo, B.A., Sasaki, S., Highasiyama, K., Sukardiman, Siswandono, and Budiati, T., 2012, Structure modification of ethyl p-methoxycinnamate and their bioassay as chemopreventive agent against mice’s fibrosarcoma, Int. J. Pharm. Pharm. Sci., 4 (Suppl. 3), 528–532.

[10] Komala, I., Supandi, Nurhasni, Betha, O.S., Yardi, Mufidah, S., Reza, M., Ali, M.S., Aulia, N.S., and Sutar, 2017, Microwave-assisted synthesis of p-methoxycinnamamides and p-methoxy-β-nitrosytrenes from ethyl p-methoxycinnamate and screening their anti-inflammatory activity, Nat. Prod. Commun., 12 (8), 1265–1268.

[11] Mahesh, M., Murphy, J.A., and Wessel, H.P., 2005, Novel deoxygenation reaction of epoxides by indium, J. Org. Chem., 70 (10), 4118–4123.

[12] Hatsuda, M., Kuroda, T., and Seki, M., 2003, An improved synthesis of (E)-cinnamic acid derivatives via the Claisen–Schmidt condensation, Synth. Commun., 33 (3), 427–434.

[13] Williams, L.A.D., O’Connar, A., Latore, L., Dennis, O., Ringer, S., Whittaker, J.A., Conrad, J., Vogler, B., Rosner, H., and Kraus, W., 2008, The in vitro anti-denaturation effects induced by natural products and non-steroidal compounds in heat treated (Immunogenic) bovine serum albumin is proposed as a screening assay for the detection of anti-inflammatory compounds, without the use of animals in the early stages of the drug discovery process, West Indian Med. J., 57 (4), 327–331.

[14] Komala, I., Azrifitria, Yardi, Suzanti, B.O., Muliati, F., and Ni’mah, M., 2015, Antioxidant and anti-inflammatory activity of the Indonesian ferns, Nephrolepisfalcata and Pyrrosia lanceolata, Int. J. Pharm. Pharm. Sci., 7 (12), 162–165.

DOI: https://doi.org/10.22146/ijc.26162