2. Academic Validation
  3. 1-Phenyl-β-carboline-3-carboxamide-1,2,3-triazole-N-phenylacetamide hybrids as new α-glucosidase inhibitors

1-Phenyl-β-carboline-3-carboxamide-1,2,3-triazole-N-phenylacetamide hybrids as new α-glucosidase inhibitors

  • Sci Rep. 2025 May 20;15(1):17418. doi: 10.1038/s41598-025-99807-x.
Elham Safaie # 1,  Mohammad Hosein Sayahi # 2,  Navid Dastyafteh 1,  Mohammad Halimi 3,  Milad Noori 1,  Maryam Mohammadi-Khanaposhtani 4,  Afsaneh Zonouzi 5,  Roghieh Mirzazadeh 6,  Azadeh Tajmir-Riahi 5,  Somayeh Mojtabavi 7,  Mohammad Ali Faramarzi 7,  Bagher Larijani 1,  Mehdi Asadi 8 9,  Mohammad Mahdavi 1
Affiliations

Affiliations

  • 1 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Department of Chemistry, Payame Noor University, Tehran, Iran.
  • 3 Department of Biology, Babol Branch, Islamic Azad University, Babol, Iran.
  • 4 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 5 School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
  • 6 Biochemistry Department, Pasteur Institute of Iran, Tehran, Iran.
  • 7 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 8 Razi Drug Research Center, University of Medical Sciences, Tehran, Iran. asadi.meh@iums.ac.ir.
  • 9 Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran. asadi.meh@iums.ac.ir.
  • # Contributed equally.
PMID: 40394178 DOI: 10.1038/s41598-025-99807-x
Abstract

In this work, 1-phenyl-β-carboline-3-carboxamide-1,2,3-triazole-N-phenylacetamide skeleton as a novel scaffold was designed based on hybridization of moieties that were found in the potent α-glucosidase inhibitors. Fourteen derivatives 14a-n of this scaffold were synthesized by the efficient chemical reactions. In vitro anti-α-glucosidase assay demonstrated that all the new fourteen derivatives with IC50 values ranging from 64.0 to 661.4 µM were more potent than positive control acarbose with IC50 value of 750.0 and in vitro kinetic study revealed that the most potent compound among them, compound 14b, was an uncompetitive α-glucosidase inhibitor. Moreover, determination of the circular dichroism (CD) spectra demonstrated that compound 14b altered the secondary structure of α-glucosidase. Prediction of the pharmacokinetics and toxicity of the most potent compound 14b showed that our new compound had good toxicity profile as an oral drug candidate. Based on these findings, compound 14b can be considered as a promising candidate for the development of a new α-glucosidase inhibitor.

Keywords

1,2,3-Triazole; α-Glucosidase; β-Carboline.

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