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Abstract

Synthesis, ADME/T, and Carbonic Anhydrase Binding of Hydroxycarboxamide Compounds †

1
Laboratory of Applied Organic Chemistry, Bioorganic Chemistry Group, Chemistry Department, Sciences Faculty, Badji-Mokhtar-Annaba University, Box 12, Annaba 23000, Algeria
2
Environment, Modeling and Climate Change Department, Environmental Research Center (CRE), Annaba 23000, Algeria
*
Author to whom correspondence should be addressed.
Presented at the 8th International Electronic Conference on Medicinal Chemistry, 1–30 November 2022; Available online: https://ecmc2022.sciforum.net/.
Med. Sci. Forum 2022, 14(1), 6; https://doi.org/10.3390/ECMC2022-13446
Published: 1 November 2022
(This article belongs to the Proceedings of The 8th International Electronic Conference on Medicinal Chemistry)

Abstract

:
The interconversion of carbon dioxide and the bicarbonate ion is carried out by carbonic anhydrases (CA), which are ubiquitous metalloenzymes with Zn in their active site. Disorder of CA enzymes can cause several diseases such as glaucoma, epilepsy, obesity, and cancer. Many existing drugs have shown effective inhibition of CAs including Acetazolamide, Dorzolamide, Methazolamide, and Valdecoxib. In order to conceive new agents inhibiting CAs, two small molecules were synthesized and characterized by the usual spectroscopic methods. The prepared compounds were obtained by the condensation of dimedone and cyclohexanedione with CSI (chlorosulfonyl isocyanate) in the presence of methanol as a proton donor. The synthesized derivatives contain a primary amide group (CONH2) bio-isostere of the sulfonamide group (SO2NH2) which is present in the quasi-totality of CAs inhibitors. The interactions between our new synthesized molecules and the active site of CAII were determined using docking simulation (PDB: 2AW1); the results showed great stability of these compounds inside the active site with the presence of metallic and hydrogen bonds similar to the ones present between CAII and the reference Valdecoxib. Pharmacokinetic properties and toxicity were predicted using in silico tool SwissADME and Molsoft.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/ECMC2022-13446/s1.

Author Contributions

Conceptualization, A.B.; methodology, A.B. and Y.O.B.; software, A.B.; validation, A.B., Y.O.B., R.M. and N.-E.A.; formal analysis, A.B.; investigation, A.B. and Y.O.B.; writing—original draft preparation, A.B.; writing—review and editing, A.B., Y.O.B., R.M., and N.-E.A. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Bouzina, A.; Bouone, Y.O.; Mansouri, R.; Aouf, N.-E. Synthesis, ADME/T, and Carbonic Anhydrase Binding of Hydroxycarboxamide Compounds. Med. Sci. Forum 2022, 14, 6. https://doi.org/10.3390/ECMC2022-13446

AMA Style

Bouzina A, Bouone YO, Mansouri R, Aouf N-E. Synthesis, ADME/T, and Carbonic Anhydrase Binding of Hydroxycarboxamide Compounds. Medical Sciences Forum. 2022; 14(1):6. https://doi.org/10.3390/ECMC2022-13446

Chicago/Turabian Style

Bouzina, Abdeslem, Yousra Ouafa Bouone, Rachida Mansouri, and Nour-Eddine Aouf. 2022. "Synthesis, ADME/T, and Carbonic Anhydrase Binding of Hydroxycarboxamide Compounds" Medical Sciences Forum 14, no. 1: 6. https://doi.org/10.3390/ECMC2022-13446

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