Synthesis of Fluorinated Hydrazinylthiazole Derivatives: A Virtual and Experimental Approach to Diabetes Management

Mehmood, Hasnain; Akhtar, Tashfeen; Haroon, Muhammad; Khalid, Muhammad; Woodward, Simon; Asghar, Muhammad Adnan; Baby, Rabia; Orfali, Raha; Perveen, Shagufta

Abstract

A novel series of fluorophenyl-based thiazoles was synthesized following the Hanztsch method. All of the compounds were initially verified with physical parameters (color, melting point, retardation factor (Rf)), which were further confirmed by several spectroscopic methods, including ultraviolet-visible (UV-visible), Fourier-transform infrared (FTIR), 1H, 13C, 19F NMR, and high-resolution mass spectrometry (HRMS). The binding interactions of all compounds were studied using a molecular docking simulation approach. Furthermore, each compound was evaluated for its alpha(α)-amylase, antiglycation, and antioxidant potentials. The biocompatibility of all compounds was checked with an in vitro hemolytic assay. All synthesized scaffolds were found biocompatible with minimal lysis of human erythrocytes as compared to the standard Triton X-100. Among the tested compounds, the analogue 3h (IC50 = 5.14 ± 0.03 μM) was found to be a highly potent candidate against α-amylase as compared to the standard (acarbose, IC50 = 5.55 ± 0.06 μM). The compounds 3d, 3f, 3i, and 3k exhibited excellent antiglycation inhibition potential with their IC50 values far less than the standard amino guanidine (IC50 = 0.403 ± 0.001 mg/mL). The antidiabetic potential was further supported by docking studies. Docking studies revealed that all synthesized compounds exhibited various interactions along enzyme active sites (pi-pi, H-bonding, van der Waals) with varied binding energies.

Citation

Mehmood, H., Akhtar, T., Haroon, M., Khalid, M., Woodward, S., Asghar, M. A., Baby, R., Orfali, R., & Perveen, S. (2023). Synthesis of Fluorinated Hydrazinylthiazole Derivatives: A Virtual and Experimental Approach to Diabetes Management. ACS Omega, 8(12), 11433-11446. https://doi.org/10.1021/acsomega.3c00265

• Journal Article Type: Article
• Acceptance Date: Mar 7, 2023
• Online Publication Date: Mar 17, 2023
• Publication Date: Mar 28, 2023
• Deposit Date: Apr 4, 2023
• Publicly Available Date: Apr 4, 2023
• Journal: ACS Omega
• Electronic ISSN: 2470-1343
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 12
• Pages: 11433-11446
• DOI: https://doi.org/10.1021/acsomega.3c00265
• Keywords: Binding energy, Inhibition, Ligands, Monomers, Peptides and proteins
• Public URL: https://nottingham-repository.worktribe.com/output/18817701
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsomega.3c00265