Novel Re(I) tricarbonyl coordination compounds based on 2-pyridyl-1,2,3-triazole derivatives bearing a 4-amino-substituted benzenesulfonamide arm: synthesis, crystal structure, computational studies and inhibitory activity against carbonic anhydrase I, II, and IX isoforms†

Yassine Aimene; Romain Eychenne; Sonia Mallet-Ladeira; Nathalie Saffon; Jean-Yves Winum; Alessio Nocentini; Claudiu T Supuran; Eric Benoist; Achour Seridi

doi:10.1080/14756366.2019.1585835

Novel Re(I) tricarbonyl coordination compounds based on 2-pyridyl-1,2,3-triazole derivatives bearing a 4-amino-substituted benzenesulfonamide arm: synthesis, crystal structure, computational studies and inhibitory activity against carbonic anhydrase I, II, and IX isoforms†

J Enzyme Inhib Med Chem. 2019 Dec;34(1):773-782. doi: 10.1080/14756366.2019.1585835.

Authors

Yassine Aimene^{1

2

3}, Romain Eychenne^{2

3}, Sonia Mallet-Ladeira⁴, Nathalie Saffon⁴, Jean-Yves Winum⁵, Alessio Nocentini⁶, Claudiu T Supuran⁶, Eric Benoist^{2

3}, Achour Seridi¹

Affiliations

¹ a Laboratoire de Chimie, physique Université du 8 Mai 1945 , Guelma , Algérie.
² b CNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, SPCMIB , Toulouse , France.
³ c Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, SPCMIB , Toulouse , France.
⁴ d Institut de Chimie de Toulouse (FR 2599) , Toulouse , France.
⁵ e Institut des Biomolécules Max Mousseron, ENSCM, Université de Montpellier , Montpellier , France.
⁶ f Neurofarba Department , Section of Pharmaceutical and Nutriceutical Sciences, Università degli Studi di Firenze , Florence , Italy.

Abstract

In this work, two bidentate 2-pyridyl-1,2,3-triazole ligands (3a and 3b) containing a 4-substituted benzenesulfonamide pharmacophore prepared by classical click chemistry procedures, as well as their corresponding rhenium complexes, 4a and 4b of general formula [ReCl(CO)₃(L)] (L = 3a or 3b) were prepared and fully characterised by spectroscopic methods (IR, NMR, MS, UV-Vis), elemental analysis, X-ray diffraction, and theoretical studies using DFT and TD-DFT methods. In particular, we showed that, in the solid state, the pyridine and the triazole rings of 3b adopted an uncommon cis configuration which stems from intermolecular hydrogen bonds. Preliminary assays demonstrated a promising nanomolar inhibitory activity against carbonic anhydrase isoform IX for both ligands and complexes with a strong affinity K_i of 2.8 nM for ligand 3a. More interestingly, complex 4b exhibited a pronounced selectivity against hCA IX over the off-targets hCA I and hCA II which makes this compound a promising potential anticancer drug candidate.

Keywords: Click chemistry; DFT calculations; carbonic anhydrase inhibitors; crystal structures; rhenium(I) complexes.

MeSH terms

Antigens, Neoplasm / metabolism
Benzenesulfonamides
Carbon Monoxide / chemistry
Carbon Monoxide / pharmacology
Carbonic Anhydrase I / antagonists & inhibitors*
Carbonic Anhydrase I / metabolism
Carbonic Anhydrase II / antagonists & inhibitors*
Carbonic Anhydrase II / metabolism
Carbonic Anhydrase IX / antagonists & inhibitors*
Carbonic Anhydrase IX / metabolism
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Crystallography, X-Ray
Density Functional Theory*
Dose-Response Relationship, Drug
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Models, Molecular
Molecular Structure
Rhenium / chemistry
Rhenium / pharmacology
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology
Triazoles / chemistry
Triazoles / pharmacology

Substances

Antigens, Neoplasm
Carbonic Anhydrase Inhibitors
Isoenzymes
Sulfonamides
Triazoles
Rhenium
Carbon Monoxide
Carbonic Anhydrase I
Carbonic Anhydrase II
CA2 protein, human
CA9 protein, human
Carbonic Anhydrase IX

Grants and funding

This research was supported in part by the Algerian Minister of High Education and Scientific Research through the National Programme Exceptional (PNE, Ph.D. fellowship A.Y.) and CNEPRUE project B00L01UN2401201400148.