Synthesis, DPPH Radical Scavenging, Cytotoxic Activity, and Apoptosis Induction Efficacy of Novel Thiazoles and Bis-thiazoles

Amr Negm; Yasair S Al-Faiyz; Sayed Riyadh; Abdelwahed R Sayed

doi:10.2174/0115701794264504231017113027

Synthesis, DPPH Radical Scavenging, Cytotoxic Activity, and Apoptosis Induction Efficacy of Novel Thiazoles and Bis-thiazoles

Curr Org Synth. 2023 Nov 2. doi: 10.2174/0115701794264504231017113027. Online ahead of print.

Authors

Amr Negm^{1

2}, Yasair S Al-Faiyz¹, Sayed Riyadh^{3

4}, Abdelwahed R Sayed⁵

Affiliations

¹ Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
² Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt.
³ Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
⁴ Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Almunawrah 30002, Saudi Arabia.
⁵ Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-suef 62514, Egypt.

PMID: 37936471
DOI: 10.2174/0115701794264504231017113027

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, invitro anti-proliferative, 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, invitro 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.

Keywords: Hydrazonoyl; anti-cancer; anti-proliferative agents; antioxidant; apoptosis; thiazole.