Insights from in silico exploration of major curcumin analogs targeting human dipeptidyl peptidase IV

Abstract

The goal of this work is to use a variety of in-silico techniques to identify anti-diabetic agents against DPP-IV enzyme from five main curcumin analogues. To produce the successful molecules, five main curcumin analogues were docked into the active site of DPP-IV enzyme. In comparison to the control molecule (Saxagliptin, −6.9 kcal/mol), all the compounds have the highest binding affinity (-7.6 to −7.7 kcal/mol) for the DPP-IV enzyme. These compounds underwent further testing for studies on drug-likeness, pharmacokinetics, and acute toxicity to see the efficacy and safety of compounds. To assess the stability of the docking complex and the binding posture identified during the docking experiment, our study got THC as the lead compound, which was then exposed to 200 ns of molecular dynamic simulation and PCA analysis. Additionally, DFT calculations were conducted to determine the thermodynamic, molecular orbital, and electrostatic potential characteristics of lead compound. Overall, the lead chemical has shown strong drug-like properties, is non-toxic, and has a sizable affinity for the DPP-IV enzyme.

Communicated by Ramaswamy H. Sarma

Keywords:

• Anti-diabetic
• curcumin
• in-silico
• docking
• MD simulation
• DFT

Acknowledgements

The authors would like to thank Universiti Malaysia Pahang Al-Sultan Abdullah for laboratory facilities.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

MR searched the Data, performed the experiments, and drafted the manuscript. AD, ARI, MNU and AT performed the experiments and drafted the manuscript. UG, AW and MFFMA reviewed and edited the manuscript. NBZ fund acquisition. MFFMA conceptualized, designed, and supervised the work.

Additional information

Funding

The authors would like to thank the Ministry of Higher Education for providing financial support under Fundamental Research Grant Scheme (FRGS) No. FRGS/1/2021/SKK06/UMP/01/1 (University reference RDU210140)