Synthesis and Anti-Colon Cancer Activity of 1,2,4-Triazole Derivatives with Aliphatic S-Substituents

Abstract

A series of new 3-mercapto-1,2,4-triazoles have been designed, synthesized and their structures were identified by nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectrophotometric techniques. The target compounds are designed as analogues for the anti-cancer agent Combretastatin A-4 with different aliphatic side substituents. The synthesized novel heterocyclic compounds were evaluated as anticancer molecules against colon cancer cell line (SW480) using the crystal violet cytotoxicity assay. The results revealed that these compounds have growth inhibitive effect on the cancer cells with different inhibition levels. Compound 5a with -SMe group was found to be the most active one with 77.4% cell growth inhibition and 10 µM IC50 value, it was also found to have relatively low cytotoxicity when tested against Madin-Darby Canine Kidney (MDCK) normal cells line. The levels of the antioxidant total capacity of the synthesized triazoles have been determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay against ascorbic acid as a reference antioxidant agent at 50 μM. Compound 4 showed highest antioxidant activity with DPPH radical scavenging capacity of 71%.

New Combretastatin Analogs as Anticancer Agents: Design, Synthesis, Microtubules Polymerization Inhibition, and Molecular Docking Studies

“…The overall process for synthesizing the desired 1,2,4 triazole CA‐4 analogs is depicted in Scheme 1. Compounds S1 and S2 were synthesized and characterized based on previous research [33] . Compound S2 (ester) was treated with hydrazine hydrate to produce the hydrazide derivative (compound 1 ) [34] .…”

“…Compounds S1 and S2 were synthesized according to previous reports. [33] The 1 H-NMR spectra were recorded on Bruker (BioSpin 400 MHz) spectrometer, chemical shift values δ (ppm) were reported to tetramethylsilane (TMS), as an internal reference, CD 2 Cl 2 and DMSO d6 were used as solvents. FT-IR spectra were measured on a Tensor II, Bruker-Optics FT-IR spectrophotometer, as KBr disc.…”

Synthesis and characterization of new 1,2,4-triazole anticancer scaffold derivatives: In Vitro study

“…S7, supporting information). Chowrasia et a.l [46] synthesized a series synthesized as series of fluorinated 3,6-diaryl- [1,2,4] [47] with IC50 for most compounds is >200 µM regarding HEPG2 and MCF-7. For MCF-7, only one compound showed IC50 less than our synthesized TB-NO2 and TB-OCH3 with IC50= 10.92 µM, and for HEPG2, three compounds were more potent than TB-NO2 and TB-OCH3.…”

“…The IC50 for compounds 5a-5d are higher than TB-NO2 and TB-OCH3, while compounds 1a-1d showed lower IC50. Kamel et al, [49] synthesized a series of new Nsubstituted-3-mercapto-1,2,4-triazoles (3a,b and 7ad), triazolo [1,3,4]thiadiazines (5a,b) and triazolo- [1,3,4]thiadiazoles (4a-d, 6 and 8a-d) and screened for their cytotoxicity against a variety of cancer cell lines. For N-substituted-3-mercapto-1,2,4-triazoles 3a,b and 7a-d, the IC50 values are 0.053, 0.089, 2.022, 1.299, 1.230, and 2.782 µM for HEPG2 respectively, while the IC50 values of MCF for the same compounds are 2.102, 1.092, 3.231, 1.672, 2.170, 1.592 µM respectively.…”

“…Cancer, which defined as uncontrolled proliferation, invasion, and metastasis of abnormal cells, is considered to be one of the most challenges in the medical world [1,2]. It represents the second lethal disease after cardiovascular diseases [3,4]. The development and discovering of new efficient anticancer drugs with highly selectivity considered a large challenge face the modern community.…”