Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid

  • Sci Rep. 2024 May 18;14(1):11410. doi: 10.1038/s41598-024-62034-x.
Hammad Khan  1 ,  Faheem Jan  2  3 ,  Abdul Shakoor  4 ,  Ajmal Khan  5 ,  Abdullah F AlAsmari  6 ,  Fawaz Alasmari  6 ,  Saeed Ullah  5 ,  Ahmed Al-Harrasi  7 ,  Momin Khan  8 ,  Shaukat Ali  9
Affiliations
  • 1. Organic Synthesis and Catalysis Research Laboratory, Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan.
  • 2. Shenyang National Laboratory for Materials Science, Institute of Metal Research Chinese Academy of Sciences, Shenyang, 110016, Liaoning, China.
  • 3. School of Materials Science and Engineering, University of Science and Technology of China, Shenyang, 110016, Liaoning, China.
  • 4. Department of Chemistry, Abdul Wali Khan University, Mardan, 23200, Pakistan.
  • 5. Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616, Birkat Al Mauz, Nizwa, Oman.
  • 6. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
  • 7. Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616, Birkat Al Mauz, Nizwa, Oman. [email protected].
  • 8. Department of Chemistry, Abdul Wali Khan University, Mardan, 23200, Pakistan. [email protected].
  • 9. Organic Synthesis and Catalysis Research Laboratory, Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. [email protected].
PMID: 38762658 DOI: 10.1038/s41598-024-62034-x
Abstract

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff Bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

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