Abstract

Jilly Octaria Tagore Chan¹, Ade Arsianti^2,3,Maurin Marcelia¹, Stevano Julio Wijoyo¹, Fadilah Fadilah^2,3,Rista Putrianingsih², Norma Nur Azizah³, Hiroki Tanimoto⁴ and Kiyomi Kakiuchi⁴

DOI : http://dx.doi.org/10.13005/ojc/340323

The natural phenolic gallic acid has demonstrated a significant inhibition of cell proliferation in a series of cancer cell lines, as well as induced apoptosis in  HCT-116 colon cancer cells. This research aims to synthesize six compounds of 3,4,5-trihydroxy-N-alkyl-benzamide derivatives of  gallic acid, and investigate its anticancer effect on colon carcinoma HCT-116 cells.Six compounds of 3,4,5-trihydroxy-N-alkyl-benzamide, namely 3,4,5-trihydroxy-N-methyl-benzamide (2); 3,4,5-trihydroxy-N-ethyl-benzamide (3); 3,4,5-trihydroxy-N-butyl-benzamide (4); 3,4,5-trihydroxy-N-sec-butyl-benzamide (5); 3,4,5-trihydroxy-N-tert-butyl-benzamide (6) and 3,4,5-trihydroxy-N-hexyl-benzamide (7), have been successfully synthesized by amidation of carboxyl group of gallic acid with six corresponding alkylamines, respectively. Furthermore, anticancer effect of these six synthesized derivatives on colon HCT-116 cells were examined by MTT assay. Data were analyzed by linear regression method to generate IC₅₀ value. The results will be compared with gallic acid as an original compound and doxorubicine as a positive control.Amidation of gallic acid with six corresponding alkylamines gave desired -N-methyl-, -N-ethyl-, -N-butyl-, -N-sec-butyl-, -N-ters-butyl-, and –N-hexyl benzamide with yield ranging from 18% to 84%. Compared to gallic acid (IC₅₀: 0.05 µM) and doxorubicine (IC₅₀: 0.001 µM), all these six synthesized derivatives showed a lower anticancer effect on colon HCT-116 cells. The strongest anticancer and inhibitory effect on HCT-116 cells has shown by 3,4,5-trihydroxy-N-hexyl benzamide (7) with IC₅₀ value of 0.07 µM. Our results suggested that 3,4,5-trihydroxy-N-hexyl benzamide (7) is a potential to be developed as a promising anti-colon cancer agent.

Synthesis; Anticancer; Gallic Acid; 3,4,5-trihydroxy-N-alkyl-benzamide; HCT-116 Cells

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