Evaluation of synthesized methoxy chalcones for therapeutic potential through in vitro and in silico methods

Abstract

Chalcones are the precursors of flavonoids and have a wide range of biological activities. A series of methoxy chalcones (1-12) were synthesized using the Claisen-Schmidt method and identified by NMR analyses. Enzyme inhibition, antimicrobial, and antioxidant activities of all compounds were investigated. The enzyme kinetics and ADMET profile of the compounds were evaluated by in silico methods. The highest inhibition activities for lipase, AChE, BChE, tyrosinase, α-amylase, and α-glucosidase were observed at the following IC50 values (μg/mL): 7 (39.83±1.1216), 2 (60.39±1.24), 1 (39.79±1.29), 2 (40.40±1.01), 1 (98.61±3.17), and 2 (55.91±1.78), respectively. Compounds 1 and 4 exhibited the highest antioxidant activity against FRAP and CUPRAC tests, while 1 and 3 were the most effective in the DPPH method. All compounds showed the best activity against gram (-) bacteria. The top docking scores were compound 1 against α-amylase and BChE, 2 against α-glucosidase, AChE, and tyrosinase, and 7 against lipase. All compounds met the drug-likeness criteria using the SwissADME. All compounds have high bioavailability with lower toxicity profiles using SwissADME and pkCSM. According to the AMES test, compounds 3, 6, 9, and 10 were predicted to be mutagenic. ProTox (v.3.0) predicts that all compounds have an oral LD50 value of 2100 mg/kg bw and are classified as GHS Category V, indicating relatively low acute toxicity. Overall, the study results indicate that compounds 1 and 2 show promise for animal studies targeting Alzheimer's disease and diabetes, while 7 appears promising for obesity.

Keywords

• Chalcones
• Molecular docking
• ADMET
• Enzyme inhibition
• Antimicrobial
• Antioxidant

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