Title:Synthesis, DPPH Radical Scavenging, Cytotoxic Activity, and Apoptosis
Induction Efficacy of Novel Thiazoles and Bis-thiazoles
Volume: 21
Issue: 8
Author(s): Amr Negm, Yasair S. Al-Faiyz, Sayed M. Riyadh and Abdelwahed R. Sayed*
Affiliation:
- Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-suef, 62514, Egypt
Keywords:
Hydrazonoyl, thiazole, antioxidant, anti-cancer, anti-proliferative agents, apoptosis.
Abstract:
Background: Heterocyclic materials-containing thiazoles exhibited incredible importance
in pharmaceutical chemistry and drug design due to their extensive biological properties.
Methods: Synthesis of thiazoles and bis-thiazoles from the reaction of 2-((6-Nitrobenzo[
d][1,3]dioxol-5-yl)methylene)hydrazine-1-carbothioamide with hydrazonoyl chlorides in
dioxane and in the existence of triethylamine as basic catalyst. The antioxidant, in vitro antiproliferative,
and cytotoxicity efficacy of thiazoles and bis-thiazoles were measured.
Results: In this work, novel series of 5-methyl-2-(2-(-(6-nitrobenzo[d][1,3]dioxol-5-yl)methylene)
hydrazinyl)-4-(aryldiazenyl)thiazoles (4a-f) were prepared via the reaction of hydrazonoyl
chlorides 2a-f with 2-((6-nitrobenzo[d][1,3]dioxol-5-yl)methylene)hydrazine-1-carbothioamide
(1) in dioxane and employing triethylamine as basic catalyst. Following the same procedure, bisthiazoles
(6, 8, and 10) have been synthesized by utilizing bis-hydrazonoyl chlorides (5, 7, and 9)
and carbothioamide 1 in a molar ratio (1:2), respectively. The distinctive features in the structure
of isolated products were elucidated by spectroscopic tools and elemental analyses. The antioxidant,
in vitro anti-proliferative, cytotoxicity, and anti-cancer efficacy of thiazoles and bis-thiazoles
were evaluated. Compounds 4d and 4f were the most potent antioxidant agents. Gene expression
of apoptosis markers and fragmentation assay of DNA were assessed to explore the biochemical
mechanism of synthesized products. Thiazoles significantly inhibited cell growth and
proliferation more than bis-thiazoles. They induced apoptosis through induction of apoptotic gene
expression P53 and downregulation of antiapoptotic gene expression Bcl-2. Moreover, they induced
fragmentation of DNA in cancer cells, indicating that they could be employed as anticancer
agents by inhibiting tumor growth and progression and can be considered effective compounds
in the strategy of anti-cancer agents’ discovery.
Conclusion: Synthesis, DPPH Radical Scavenging, Cytotoxic activity, and Apoptosis Induction
Efficacy based on Novel Thiazoles and Bis-thiazoles.
