2. Academic Validation
  3. Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors

Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors

  • Sci Rep. 2022 Sep 27;12(1):16095. doi: 10.1038/s41598-022-19975-y.
Asif Rasool 1,  Zahra Batool 1,  Majid Khan 2,  Sobia Ahsan Halim 2,  Zahid Shafiq 3 4,  Ahmed Temirak 5,  Mohamed A Salem 6 7,  Tarik E Ali 8 9,  Ajmal Khan 10,  Ahmed Al-Harrasi 11
Affiliations

Affiliations

  • 1 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan.
  • 2 Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman.
  • 3 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan. zahidshafiq@bzu.edu.pk.
  • 4 Department of Pharmaceutical and Medicinal Chemistry, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany. zahidshafiq@bzu.edu.pk.
  • 5 National Research Centre, Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, Dokki, P.O. Box 12622, Cairo, Egypt.
  • 6 Department of Chemistry, Faculty of Science and Arts, King Khalid University, Muhayil, Assir, Saudi Arabia.
  • 7 Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt.
  • 8 Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia.
  • 9 Department of Chemistry, Faculty of Education, Ain Shams University, Cairo, Egypt.
  • 10 Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman. ajmalkhan@unizwa.edu.om.
  • 11 Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman. aharrasi@unizwa.edu.om.
PMID: 36167735 DOI: 10.1038/s41598-022-19975-y
Abstract

Here, we report the synthesis, carbonic anhydrase-II (CA-II) inhibition and structure-activity relationship studies of cinnamaldehyde-clubbed thiosemicarbazones derivatives. The derivatives showed potent activities in the range of 10.3 ± 0.62-46.6 ± 0.62 µM. Among all the synthesized derivatives, compound 3n (IC50 = 10.3 ± 0.62 µM), 3g (IC50 = 12.1 ± 1.01 µM), and 3h (IC50 = 13.4 ± 0.52 µM) showed higher inhibitory activity as compared to the standard inhibitor, acetazolamide. Furthermore, molecular docking of all the active compounds was carried out to predict their behavior of molecular binding. The docking results indicate that the most active hit (3n) specifically mediate ionic interaction with the Zn ion in the active site of CA-II. Furthermore, the The199 and Thr200 support the binding of thiosemicarbazide moiety of 3n, while Gln 92 supports the interactions of all the compounds by hydrogen bonding. In addition to Gln92, few Other residues including Asn62, Asn67, The199, and Thr200 play important role in the stabilization of these molecules in the active site by specifically providing H-bonds to the thiosemicarbazide moiety of compounds. The docking score of active hits are found in range of - 6.75 to - 4.42 kcal/mol, which indicates that the computational prediction correlates well with the in vitro results.

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