Sains Malaysiana 51(4)(2022): 1085-1097

http://doi.org/10.17576/jsm-2022-5104-11

Phenethyl p-coumarate and N-phenethyl-p-coumaramide: Synthesis, Characterization, Docking Studies and Anticancer Activity through P388 Cell

(Fenetil p-kumarat dan N-fenetil-p-kumaramida: Sintesis, Pencirian, Kajian Mengedok dan Aktiviti Antikanser melalui Sel P388)

FIRDAUS^1,*, NUNUK HARIANI SOEKAMTO¹, SENIWATI¹, SYADZA FIRDAUSIAH¹, HERLINA RASYID¹, BAHJA² & MUHAMMAD FAJAR ISLAM¹

¹Department of Chemistry, Faculty of Mathematics and Sciences, Hasanuddin University Makassar, 90245, Indonesia

²Department of Nutrition, State Health Polytechnic of Palu, Palu 94148, Indonesia

Received: 30 April 2021/Accepted: 1 September 2021

ABSTRACT

Most p-coumaric acid derivatives and molecules containing phenethyl moiety have a potential in anticancer activity. Thus, combining a p-coumaroyl group and a phenethyl moiety in one compound will increase anticancer activity. The principal objective of this research was to incorporate p-coumaroyl and phenethyl moieties to form an ester, phenethyl p-coumarate (5), and an amide, N-phenethyl-p-coumaramide (6), then tested their anticancer activity using P388 leukemia murine cells. The characterization by FTIR method, compound 5 gave a strong absorption band of alkyl C-O bond that appears at 1165,00 cm^-1, and compound 6 gave a sharp and medium absorption band of N-H bond that appears at 3396.64 cm^-1. Docking studies of both compounds showed a hydrogen bond with Ile839 residue, and an additional hydrogen bond appeared between compound 6 and Ser991 residue. Based on their activity against P388 leukemia murine cells, these compounds are more active than their analog compounds of N-feruloylpiperidine and N-feruloylmorpholine, which have been synthesized previously.  Compounds 5 and 6 have a high potential to be used as anticancer drugs.

Keywords: Anticancer; docking; N-phenethyl-p-coumaramide; p-coumaric acid; phenethyl p-coumarate

ABSTRAK

Sebilangan besar molekul dan terbitan asid p-kumarat yang mengandungi fenetil fenil mempunyai potensi aktiviti antikanser. Oleh itu, menggabungkan kumpulan p-koumaroyl dan gugus fenil dalam satu sebatian akan meningkatkan aktiviti antikanser. Objektif utama penyelidikan ini adalah untuk menggabungkan bahagian p-koumaroyl dan fenetil untuk membentuk ester, fenetil p-kumarat (5) dan amida, N-fenetil-p-kumaramida (6), kemudian menguji aktiviti antikanser menggunakan sel P388 leukemia murin. Pencirian dengan kaedah FTIR, sebatian 5 memberikan jalur penyerapan yang kuat di ikatan alkil C-O yang muncul pada 1165,00 cm^-1 dan sebatian 6 memberikan jalur penyerapan ikatan N-H yang tajam dan sederhana yang muncul pada 3396.64 cm^-1. Kajian mengedok untuk kedua-dua sebatian menunjukkan ikatan hidrogen dengan residu Ile839 dan ikatan hidrogen tambahan muncul antara sebatian 6 dan residu Ser991. Berdasarkan aktiviti mereka terhadap sel P388 leukemia murin, sebatian ini adalah lebih aktif daripada sebatian analog N-feruloylpiperidina dan N-feruloylmorfolina, yang telah disintesis sebelumnya. Sebatian 5 dan 6 berpotensi tinggi untuk digunakan sebagai ubat antikanser.

Kata kunci: Antikanser; asid p-kumarat; fenetil p-kumarat; kajian dok; N-fenetil-p-kumaramida

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^*Corresponding author; email: firdaus@unhas.ac.id