Syntheses, Molecular Docking and Biological Evaluation of 2-(2- hydrazinyl)thiazoles as Potential Antioxidant, Anti-Inflammatory and Significant Anticancer Agents

Abstract

Background: Recently, researchers have worked on the development of new methods for the synthesis of bioactive heterocycles using polyethylene glycol as a green solvent. In this context, we report the synthesized 2-(2-hydrazinyl) thiazoles for their in vitro antioxidant, in vitro anti-inflammatory and in vitro anti-cancer activities.

Objective: The objective of the study was to develop novel antioxidant, anti-inflammatory and anti-cancer drugs.

Methods: At the outset, the condensation of substituted acetophenones 1, thiosemicarbazide 2, and α-haloketones 3 was carried out using PEG-400 (20 mL) in the presence of 5 mol% glacial acetic acid to afford thiosemicarbazones intermediate. Furthermore, these thiosemicarbazones were reacted with α-haloketones 3 to obtain appropriate 2-(2-hydrazinyl) thiazoles. The synthesized compounds were in vitro tested for their antioxidant, anti-inflammatory, and anti-cancer activity.

Results: In vitro evaluation report showed that nearly all molecules possessed potential antioxidant activity against 2,2-Diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR) and hydrogen peroxide (H₂O₂) radical scavenging activity. Most 2-(2-hydrazinyl) thiazoles derivatives have shown potential anti-inflammatory activity as compared to diclofenac sodium as a reference standard. 2-(2-Hydrazinyl) thiazoles derivatives showed significant anticancer activity for human leukemia cell line K-562 compared to adriamycin as a reference standard.

Conclusion: All tested compounds showed potential 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging activity. Among the tested series, 4b, 4d and 4e exhibited good hydrogen peroxide and 4b, 4e, 4f and 4g showed excellent superoxide radical scavenging activity. In addition, the 4b, 4e and 4g compounds revealed potent in vitro anti-inflammatory activity against standard diclofenac sodium drug. 2-(2-Hydrazinyl) thiazole derivatives, such as 4c and 4d, showed significant anticancer activity against human leukemia cell line K-562. Thus, these molecules provide an interesting template for the design and development of new antioxidant, anti-inflammatory, and anti-cancer agents.

Keywords: 2-(2- Hydrazinyl)thiazoles; Antioxidant activity; PEG-400; anti-inflammatory activity; anticancer activity; hydrazones.; molecular docking; multicomponent reaction.