Molecular docking, derivatization, characterization and biological assays of amantadine

Abstract

Background: Derivatization has been tremendously utilized in the field of drug discovery for optimizing the pharmacological properties and improving safety, efficacy and selectivity. Methodology: Schiff’s bases (AD1–AD11) are synthesized through amantadine condensation with different aldehydes and ketones. Fourier transform infrared, ¹H NMR, ¹³C NMR, TLC, liquid chromatography mass spectrometry analysis, in silico studies, molecular docking and antiviral activity through hemagglutinin test were performed for evaluation of new compounds. Results: AD2, 3 and 9–11 showed greater antiviral activity than the parent drug. Among all derivatives, AD2 and AD3 exhibited good potential against α-amylase while AD7 and AD10 showed stronger inhibition against α-glucosidase. Conclusion: So, it is concluded that the most potent derivatives can be used as lead compounds in novel drug design of antiviral antidiabetic agents.

GRAPHICAL ABSTRACT

Article highlights

Introduction

• Literature survey of amantadine derivatives having antidiabetic and antiviral activity and objective of research.

Materials & methods

• Chemicals and instrumentation.

• General procedure for the synthesis of Schiff base derivatives of amantadine (AD1–AD11).

• Biological evaluation through in vitro studies.

• Antiviral assay.

• Hemagglutination test.

• α-amylase enzyme inhibition assay.

• Molecular docking studies.

Results

• Physical and chemical characterization.

• Derivatives with excellent antiviral, α-amylase and α-glucosidase inhibition potential synthesized compounds as good candidates against both enzymes molecular docking studies.

Conclusion

• Utilization of new compounds against hepatitis A virus, Parkinson’s disease, as well as for other hyperglycemic disorders lead compound for diabetes as well as for viral infections.

Keywords: :

• α-amylase
• α-glucosidase
• antiviral
• Schiff’s bases

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17568919.2024.2385294

Author contributions

Managing research and investigation procedures, primarily synthesizing the new derivatives, or data collection was done by Z Yasmeen. MA Khan ideally formulated and supervised the research passionately. IA provided the relevant study materials, laboratory samples, reagents, laboratory samples and instrumentation. F Ullah did the programing and software development, designing of computer programs and implementation of the computer code. Management activities to annotate (produce metadata) and scrub data was done by Breena. MT Akram maintained the research data (including software code, where it is necessary for interpreting the data itself) for initial use and later re-use. MR Khan did the overall management and proof reading. All authors have read and agreed to the published version of the manuscript.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Data availability statement

Data can be provided on demand from corresponding author.