Advantages:
- 2-Aminothiazole scaffold compounds are synthesized in aqueous condition, a practical and green approach.
- 3-component one-pot synthesis route with high reaction yield, shorter reaction time, and mild reaction conditions.
- Compounds are non-cytotoxic Nampt activators effective in promoting in vitro wound closure.
- Potential treatment for wound healing, heart disease, and skeletal muscle regeneration.
Summary:
2-Aminothiazole is a prominent structure in drug development, serving as a core component of many potential drug candidates due to its diverse biological activities, such as anticancer, antioxidant, antimicrobial, and anti-inflammatory properties. Thiazole is present in various natural products, including vitamin B1 or thiamine. However, the synthesis process of 2-aminothiazole is challenging due to its complex reaction mechanisms, high synthesis costs, limited tolerance for certain functional groups, and potential issues with low yield. Some synthesis methods may also pose environmental and safety hazards and result in unwanted by-products.
The researcher designed new 2-aminothiazole derivatives with a wide range of substitutions on the aniline aromatic ring and evaluated their potential against the Nampt enzymatic assay in vitro. Nampt (Nicotinamide Phosphoribosyltransferase) is a crucial enzyme in the biosynthesis of NAD+ and plays an important role in cryoprotection via numerous metabolic processes, including energy production, angiogenesis, DNA repair, and regulation of oxidative stress. Molecular docking was performed to fit compounds JG-49, JG-62, and KBA-18 against the Nampt enzyme, and an increase in Nampt enzymatic activity was found in vitro. These new compounds were also found to be cytoprotective and demonstrated beneficial effects on wound closure, heart disease, and skeletal muscle regeneration in an in vitro mouse model.
The researcher also discovered a three-component one-pot synthesis route using resorcinarene cavitand glycoconjugates (RCGs) under aqueous conditions. This synthesis route has several advantages such as high reaction yield, shorter reaction time, and mild reaction conditions.
Fig. 1. Nampt enzymatic activity of the 2-Aminothiazole substituted derivatives, JG49, JG62, and KBA18 at 1.0 and 10.0 µM concentrations with (+) and without (-) the recombinant Nampt enzyme. The Nampt activity was assessed by measuring the optical density at 450nm for every 5 minutes up to 30 minutes and represented as the Nampt activity per minute. The data are represented as mean ± SEM of duplicate samples/group; where, *p<0.05.
Desired Partnerships:
- License
- Sponsored Research
- Co-Development