Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents

Nagwa M Abdelazeem; Wael M Aboulthana; Ashraf S Hassan; Abdulrahman A Almehizia; Ahmed M Naglah; Hamad M Alkahtani

doi:10.1016/j.jsps.2024.102025

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents

Saudi Pharm J. 2024 May;32(5):102025. doi: 10.1016/j.jsps.2024.102025. Epub 2024 Mar 12.

Authors

Nagwa M Abdelazeem¹, Wael M Aboulthana², Ashraf S Hassan¹, Abdulrahman A Almehizia³, Ahmed M Naglah³, Hamad M Alkahtani⁴

Affiliations

¹ Organometallic and Organometalloid Chemistry Department, National Research Centre, Dokki 12622, Cairo, Egypt.
² Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki 12622, Cairo, Egypt.
³ Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7-9, 11-13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (¹H and ¹³C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure-activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays.

Keywords: Anti-diabetic and anti-Alzheimer's agent; Computational studies; Pyrazole and pyridine moieties; Structure–activity relationship study; Sulfonamide derivatives; α-Amylase and α-glucosidase enzymes.