2. Academic Validation
  3. Design, synthesis and biological evaluation of new 1,ω-Bis-(5-alkyl-3-tosyl-1,3,4,2-triazaphospholino)alkanes as in vitro α-amylase and lipase inhibitors

Design, synthesis and biological evaluation of new 1,ω-Bis-(5-alkyl-3-tosyl-1,3,4,2-triazaphospholino)alkanes as in vitro α-amylase and lipase inhibitors

  • Int J Biol Macromol. 2023 Dec 31;253(Pt 5):127195. doi: 10.1016/j.ijbiomac.2023.127195.
Salwa Hamzaoui 1,  Bochra Ben Salah 2,  Soumaya Bouguerra 3,  Khaled Hamden 4,  Othman A Alghamdi 5,  Nabil Miled 6,  Mohamed Kossentini 1
Affiliations

Affiliations

  • 1 Laboratory of Medicinal and Environnemental Chemistry, Higher Institute of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisia.
  • 2 Laboratory of Medicinal and Environnemental Chemistry, Higher Institute of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisia. Electronic address: [email protected].
  • 3 Laboratory of Electrochimistry and Environmental, Higher Institute of Ingenirous of Sfax, University of Sfax, 3038 Sfax, Tunisia.
  • 4 Laboratory of Bioresources: Integrative Biology and Exploiting, Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.
  • 5 University of Jeddah, College of Science, Department of Biological Sciences, Jeddah, Saudi Arabia.
  • 6 University of Jeddah, College of Science, Department of Biological Sciences, Jeddah, Saudi Arabia; Functional Genomics and Plant Physiology Unit, Higher Institute of Biotechnology of Sfax, 3038 Sfax, Tunisia.
PMID: 37793521 DOI: 10.1016/j.ijbiomac.2023.127195
Abstract

A series of new 1,ω-bis-(5-alkyl-3-tosyl-1,3,4,2-triazaphospholino)alkanes 2 and 3 were obtained in excellent yields by the condensation of 1,ω-bis-(1-tosylamidrazone)alkanes 1 with two equivalent molars of Lawesson's Reagent (LR) and trisdimethylaminophosphine, respectively. All synthesized compounds were characterized by various spectroscopic techniques including IR, 1H NMR, 13C NMR and 31P NMR and elemental analysis. The newly synthesized compounds were evaluated against key enzymes related to diabetes and obesity such as α-amylase and Lipase. This study showed that the compounds 3a and 2b are an excellent inhibitor of α-amylase (with IC50 = 18.8 mM) and Lipase (with IC50 = 19 mM) respectively, as compared with standard, orlistat (IC50 = 22 mM). Among this series, compounds 3a and 2b with the CH3 or C2H5 group at position 6 were identified as the most potent inhibitors against α-amylase, and Lipase enzymes. The remaining compounds were found to be moderately active. Further, molecular docking simulation studies were done to identify the interactions and binding mode of synthesized analogs at binding site of α-amylase and Lipase enzymes.

Keywords

1,ω-bis(1-tosylamidrazone)alkanes; 1,ω-bis(5-alkyl-3-tosyl-1,3,4,2-triazaphospholine-2-oxide)alkanes; Diabetes; Lawesson's reagent; Obesity; Trisdimethylaminophosphine.

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