Preferential inhibition of α-amylase by cinnamaldehyde-based hydrazones: A comparative study
Chanchal Vashisth1, Neera Raghav1
1Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136119, India.
Abstract:
The escalating issue of obesity and related health conditions, including diabetes mellitus and coronary heart disease, necessitates the development of digestive enzyme inhibitors. Targeting pancreatic lipase to inhibit fatty acid generation to attain reduced lipid absorption is a promising approach for identifying effective agents. Orlistat, the only clinically approved pancreatic lipase inhibitor, is associated with gastrointestinal side effects like oily stools, spotting, and flatulence. Concurrently, α-amylase inhibitors can mitigate rapid spikes in blood sugar levels. With the growing significance of natural products in pharmaceutical research, cinnamaldehyde has been recognized as a potential enzyme inhibitor. This study explores the effects of cinnamaldehyde-derived hydrazone Schiff bases on lipase and α-amylase through in vitro experiments. The synthesized compounds exhibited IC50 value for lipase in the same range ((0.41-12.58) × 10-8 M) as exhibited by the commercial drug orlistat (5.76 × 10-8 M). However, for α-amylase inhibition, the compounds (IC50 value = 0.37-9.54 × 10-9 M) were found effective inhibitors of acarbose (IC50 value = 6.76 × 10-6 M) and curcumin (IC50 value = 467 × 10-9 M). In silico DFT studies, molecular docking, drug likeliness, bioactivity score, ADME, and toxicity are also investigated for these compounds.
Insights
New cinnamaldehyde-derived compounds show promise as digestive enzyme inhibitors for obesity and diabetes management. These agents effectively inhibit pancreatic lipase and alpha-amylase, offering potential alternatives to existing drugs with fewer side effects.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Biochemistry
Background:
- Obesity and related conditions like diabetes mellitus and coronary heart disease are significant global health concerns.
- Current treatments, such as Orlistat for pancreatic lipase inhibition, have limitations including gastrointestinal side effects.
- Natural products are increasingly explored for pharmaceutical applications, with cinnamaldehyde identified as a potential enzyme inhibitor.
Purpose of the Study:
- To synthesize and evaluate cinnamaldehyde-derived hydrazone Schiff bases as inhibitors of pancreatic lipase and alpha-amylase.
- To compare the inhibitory potential of these novel compounds with clinically used drugs like Orlistat, acarbose, and curcumin.
- To investigate the in silico properties including drug likeness, ADME, and toxicity of the synthesized compounds.
Main Methods:
- Synthesis of novel cinnamaldehyde-derived hydrazone Schiff bases.
- In vitro enzyme inhibition assays for pancreatic lipase and alpha-amylase.
- In silico studies including DFT, molecular docking, drug likeness, ADME, and toxicity assessments.
Main Results:
- The synthesized compounds demonstrated potent inhibition of pancreatic lipase, with IC50 values comparable to Orlistat.
- These compounds also exhibited significant alpha-amylase inhibitory activity, outperforming acarbose and curcumin.
- In silico analyses supported the potential therapeutic applicability of these novel enzyme inhibitors.
Conclusions:
- Cinnamaldehyde-derived hydrazone Schiff bases represent a promising class of compounds for the development of new anti-obesity and anti-diabetic agents.
- These compounds offer a potential therapeutic strategy by inhibiting key digestive enzymes involved in lipid and carbohydrate metabolism.
- Further research and development are warranted to explore their full therapeutic potential and safety profile.
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