Exploration of newly synthesized azo-thiohydantoins as the potential alkaline phosphatase inhibitors via advanced biochemical characterization and molecular modeling approaches

Hafiz Muhammad Attaullah; Syeda Abida Ejaz; Pervaiz Ali Channar; Aamer Saeed; Rabail Ujan; Seema Zargar; Sajid Ali Channar; Reshma Sahito; Tanveer A Wani; Qamar Abbas

doi:10.1186/s13065-024-01149-8

Exploration of newly synthesized azo-thiohydantoins as the potential alkaline phosphatase inhibitors via advanced biochemical characterization and molecular modeling approaches

BMC Chem. 2024 Mar 6;18(1):47. doi: 10.1186/s13065-024-01149-8.

Authors

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan. abida.ejaz@iub.edu.pk.
³ Department of Basic Sciences and Humanities, Faculty of Information Science and Humanities, Dawood University of Engineering and Technology, Karachi, 74800, Pakistan. pervaiz.ali@duet.edu.pk.
⁴ Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan. aamersaeed@yahoo.com.
⁵ Dr. M. A. Kazi Institute of Chemistry, University of Sindh, Jamshoro, Pakistan.
⁶ Department of Biochemistry, College of Science, King Saud University, P.O.Box 22452, Riyadh, 11451, Saudi Arabia.
⁷ Department of Zoology, University of Sindh, Jamshoro, Pakistan.
⁸ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O.Box 2457, Riyadh, 11451, Saudi Arabia.
⁹ Department of Biology, College of Science, University of Bahrain, Sakhir, 32038, Kingdom of Bahrain.
¹⁰ College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju, 32588, Republic of Korea.

Abstract

In the current study, Azo-Thiohydantoins derivatives were synthesized and characterized by using various spectroscopic techniques including FTIR, ¹H-NMR, ¹³C-NMR, elemental and HRMS analysis. The compounds were evaluated for alkaline phosphatase activity and it was observed that among all the synthesized compounds, derivative 7e exhibited substantial inhibitory activity (IC₅₀ = 0.308 ± 0.065 µM), surpassing the standard inhibitor (L-Phenyl alanine, IC₅₀ = 80.2 ± 1.1 µM). Along with this, these derivatives were comprehensively examined regarding the electronic properties and reactivity of the synthesized compounds using Density Functional Theory (DFT) calculations, where the results were found very promising and the synthesized compound were found stable. After that, SwissADME evaluations highlighted compounds for their favorable physicochemical properties, including solubility and drug-likeness. Molecular docking exhibited the strong binding affinities of 7f and 7e derivatives with intestinal alkaline phosphatase (IAP), further supported by Molecular Dynamics (MD) simulations. This comprehensive integration of experimental and computational approaches sheds the light on the potential therapeutic applications of the synthesized compounds. By providing a detailed investigation of these aspects, this research opens the avenues for the development of novel pharmacologically active compounds with diverse applications.

Keywords: Alkaline phosphatase; Azo; Azo-thiohydantoins; MD simulations; Molecular docking.