2. Academic Validation
  3. Synthesis of novel 1,2,3-triazole-tethered N-acyl hydrazones as a new class of carbonic anhydrase II inhibitors: In vitro and in silico potentials

Synthesis of novel 1,2,3-triazole-tethered N-acyl hydrazones as a new class of carbonic anhydrase II inhibitors: In vitro and in silico potentials

  • Bioorg Chem. 2024 Dec:153:107822. doi: 10.1016/j.bioorg.2024.107822.
Noor Fatima 1,  Aamer Saeed 2,  Saeed Ullah 3,  Sobia Ahsan Halim 3,  Ajmal Khan 4,  Muhammad Yaseen 5,  Amara Mumtaz 6,  Muhammad Zaffar Hashmi 7,  Hesham R El-Seedi 8,  Jalal Uddin 9,  Ahmed Al-Harrasi 10
Affiliations

Affiliations

  • 1 Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
  • 2 Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: asaeed@qau.edu.pk.
  • 3 Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman.
  • 4 Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman; Department of Chemical and Biological Engineering, College of Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
  • 5 Institute of Chemical Sciences, University of Swat, Charbagh, Swat 19130, Pakistan.
  • 6 Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
  • 7 Department of Environmental Health and Management, Health Services Academy Islamabad, Pakistan.
  • 8 Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
  • 9 Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
  • 10 Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman. Electronic address: aharrasi@unizwa.edu.om.
PMID: 39305609 DOI: 10.1016/j.bioorg.2024.107822
Abstract

Carbonic Anhydrase II (CA II) is crucial for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance. It is a pivotal druggable target which is implicated in glaucoma, renal, gastric, and pancreatic carcinomas, as well as in malignant brain tumours. Therefore, to identify new CA II (bovine) inhibitors, the current study was designed to synthesize a library of 20 new triazole-linked hydrazones (6a-t). All compounds were characterized by using spectroscopic techniques such as NMR and mass spectrometry. The in-vitro evaluation resulted in impressive inhibitory capability against CA II with IC50 values ranging from 9.10 ± 0.26-48.26 ± 1.30 µM. Among all derivatives, compounds 6a, 6b, 6d, 6k-6m, 6q, 6s and 6t exhibited potent inhibitory potential with 6t deemed as the most active inhibitor. Additionally, kinetic study of the hybrid 6t revealed concentration dependent type of inhibition with Ki value 7.24 ± 0.0086 µM. Furthermore, molecular docking of 6t correlates well with the kinetic analysis. The in-silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development.

Keywords

1,2,3-Triazole-tethered N-acyl hydrazones; Carbonic anhydrase II inhibitors; Molecular docking.

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