Wound healing activity of pyrazole-thiazole derivatives of curcumin through the docking, pharmacokinetics, MD simulation and MM/GBSA approaches

Md, Shaekh Forid and Miah, Roney and Uddin, Md. Nazim and A.K.M, Moyeenul Huq and Mohd Nasir, Mohd Hamzah and Mohd Aluwi, Mohd Fadhlizil Fasihi and Azuri, Muhammad Saupi and Wan Ishak, Wan Maznah (2024) Wound healing activity of pyrazole-thiazole derivatives of curcumin through the docking, pharmacokinetics, MD simulation and MM/GBSA approaches. International Journal of Chemical and Biochemical Sciences, 25 (18). pp. 83-109. ISSN 2226-9614

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Abstract

Matrix metalloproteinase (MMP-2 and MMP-8) have been found to be promising targets for the discovery and development for of novel wound healing drugs candidate. However, there are currently no MMP-2 or MMP-8 inhibitors that are therapeutically helpful for treating wound healing. Therefore, the goal of this study was to investigate the wound healing potential of novel pyrazole-thiazole derivatives of curcumin using a series of computational studies. We first utilized the physicochemical and ADMET to screen the eight curcumin analogs and the outcomes from showed that compound C2 is potential favorable compound for further exploration. The docking analysis showed that compound C2 has strong binding affinity with the MMP-2 and MMP-8 compared to reference drug. Furthermore, MD simulation result indicated C2/MMP-2 complex is more stable than C2/MMP-8 complex. Likewise, MM/GBSA results suggest that binding stability of C2/MMP-2 complex is more stable as they showed most negative binding free energy (ΔGbind -24.434 kcal/mol) compared to C2/MMP-8 complex (ΔGbind -12.347). Furthermore, PCA and FEL analysis revealed that C2/MMP-2 complex displayed stable complex formation compared to C2/MMP-8 complex in 100 ns molecular dynamics simulation trajectory. Hence, C2 could be considered a potent MMP-2 inhibitor and could be experimentally verified as a lead compound for the search for MMP-2 inhibitors for the treatment of wound healing.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Curcumin, wound healing, matrix metalloproteinases, molecular docking, MD simulation.
Subjects:	Q Science > Q Science (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science > Department of Biotechnology Kulliyyah of Science
Depositing User:	Dr Mohd Hamzah Mohd Nasir
Date Deposited:	22 Apr 2024 11:56
Last Modified:	22 Apr 2024 11:59
URI:	http://irep.iium.edu.my/id/eprint/111034

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