Synthesis, anti-diabetic and in silico QSAR analysis of flavone hydrazide Schiff base derivatives

Abstract

This study reports synthesis of flavone hydrazide Schiff base derivatives with diverse functionalities for the cure of diabetic mellitus and their a-glucosidase inhibitor and in silico studies. In this regard, Flavone derivatives 1–20 has synthesized and characterized by various spectroscopic techniques. These compounds showed significant potential towards a-glucosidase enzyme inhibition activity and found to be many fold better active than the standard Acarbose (IC₅₀ = 39.45 ± 0.11 µM). The IC₅₀values ranges 1.02–38.1 µM. Among these, compounds 1(IC₅₀ = 4.6 ± 0.23 µM), 2(IC₅₀ = 1.02 ± 0.2 µM), 3(IC₅₀ = 7.1 ± 0.11 µM), 4(IC₅₀ = 8.3 ± 0.34 µM), 5(IC₅₀ = 7.4 ± 0.15 µM), 6(IC₅₀ = 8.5 ± 0.27 µM) and 18 (IC₅₀ = 1.09 ± 0.26 µM) showed highest activity. It was revealed that the analogues having –OH substitution have higher activity than their look likes. The molecular docking analysis revealed that these molecules have high potential to interact with the protein molecule and have high ability to bind with the enzyme. Furthermore, in silico pharmacokinetics, physicochemical studies were also performed for these derivatives. The bioavailability radar analysis explored that of all these compounds have excellent bioavailability for five (5) descriptors, however, the sixth descriptor of instauration is slightly increased in all compounds.

Communicated by Ramaswamy H. Sarma

Keywords:

• Anti-diabetic
• flavone hydrazide Schiff base
• in silico pharmacokinetics analysis
• bioavailability radar studies

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors are thankful to the Higher Education Commission (HEC) Pakistan, for their financial support to Research Project No. 6727 under National Research Program for Universities (NRPU).