Synthesis and anticancer effect of 3,4,5-n-alkyl-benzamides on colon carcinoma HCT- 116 cells

Abstract

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.