Anticancer Activity of New 1,2,3-Triazole-Amino Acid Conjugates

Abstract

A multistep synthesis was developed to prepare new 1,2,3-triazole-amino acid conjugates (6 and 7). These compounds contain the diaryl ether moiety and were synthesized via SNAr reaction under mild condition and in good yield. Their structures were confirmed by spectroscopic analyses (HR-MS, NMR, IR). These compounds showed significant antiproliferative activity (>30%) toward the breast MCF7 and liver HepG2 cancer cells lines at <10 µM concentration.

Diarylether‐Amino Acid Conjugates as New Class of Anticancer Agents

“…The results showed that at 40 μM, except phenylalanine derivatives DE‐Phe‐OEt 4 c , DE‐Phe‐OH 5 c and DE‐Phe‐NHNH 2 7 c , other compounds showed unsignificant MCF‐7 inhibitory activity (<20 %). This suggests phenylalanine derivatives are more favorable for antiproliferation activity compared to other studied amino acid derivatives (Gly, Val, and Met) and in agreement with our previous study [9] . Among the phenylalanine derivatives 4 c , 5 c , and 7 c , at 40 μM, the least polar ethyl ester containing compound 4 c is the most potent with 54 % inhibitory activity while an equal activity of 36–37 % inhibitory activity was observed for carboxylic acid containing compound 5 c and hydrazide containing compound 7 c .…”

“…We hypothesized that the DE motif 1 prepared from vanillic acid and 1-fluoro-4-nitrobenzene in our previous study [9] (scheme 1) could be favourable for biological activity. In addition, we chose to conjugate this DE motif to four different natural amino acids 1) glycine for small achiral moiety, 2) valine with aliphatic hydrophobic group, 3) phenylalanine with aromaticity and 4) methionine with flexible chain contanining heteroatom.…”

“…This suggests phenylalanine derivatives are more favorable for antiproliferation activity compared to other studied amino acid derivatives (Gly, Val, and Met) and in agreement with our previous study. [9] Among the phenylalanine derivatives 4 c, 5 c, and 7 c, at 40 μM, the least polar ethyl ester containing compound 4 c is the most potent with 54 % inhibitory activity while an equal activity of 36-37 % inhibitory activity was observed for carboxylic acid containing compound 5 c and hydrazide containing compound 7 c. This suggests carboxylic acid moiety usually being negative charge under biological conditions in 5 c and additional three HBD of hydrazide moiety in 7 c are tolerated but these two compounds may have reduced cell permeability to reach intracellular target. Moreover, cell morphology and dose-response cell viability (Figure 2) of DE-Phe-OEt 4 c showed that, at low concentrations (5 μM), 4 c had no significant effect on MCF-7 cells in monolayer cultured condition (2D).…”

“…On the other hand, natural amino acid is a polar motif with increasing sp 3 fraction and aqueous solubility for oral formulation, [6,7] and specificity for target binding thanks to the unique chirality [8] . We previously synthesized two DE‐amino acid conjugates ( A , Figure 1) which contained 1,2,3‐triazole motif prepared by click chemistry and showed significant anticancer activity [9] . In this paper, we present the synthesis of a series of 13 new DE‐amino acid conjugates using amide coupling, a robust and most popular reaction in drug discovery, [10] as a key reaction and study their structure‐activity relationship (SAR) toward their anticancer activities as well as study of their mechanism of action using molecular docking.…”

Synthesis, Anticancer and Antibacterial Activity of Mannose-based bis-1,2,3-Triazole Derivatives

“…Cancer has life serious threats to global health that causes one out of six life losses in the world. 1 The triazoles derivatives revealed extensively antiproliferative potency against human prostate, 2 breast, 3 liver, 4 lung, 5 bladder 6 and other cancer cells, in drug discovery. Mimicking glycosides, Nerella and co-workers 7 built new1,2,3-triazoles based on carbohydrate molecule that have notable anticancer activity against breast and prostate cancer cell lines.…”