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. 2023 Dec;38(1):2194573.
doi: 10.1080/14756366.2023.2194573.

Inhibitory effects of sulfenimides on human and bovine carbonic anhydrase enzymes

Hasan Yakan  1 , Gürkan Bilir  2 , Şükriye Çakmak  3 , Ömer Taş  2 , Nalan Türköz Karakullukçu  4 , Ercan Soydan  2 , Halil Kütük  5 , Coşkun Güçlü  6 , Murat Şentürk  7 , Tayfun Arslan  8 , Seyhan Öztürk  5 , Ercüment Aksakal  9 , Deniz Ekinci  2
Affiliations

Inhibitory effects of sulfenimides on human and bovine carbonic anhydrase enzymes

Hasan Yakan et al. J Enzyme Inhib Med Chem. 2023 Dec.

Abstract

A series of sulfenimide derivatives (1a-i) were investigated as inhibitors of human (hCA-I, hCA-II) and bovine (bCA) carbonic anhydrase enzymes. The compounds were synthesised by the reaction of substituted thiophenols with phthalimide by means of an effective, simple and eco-friendly method and the structures were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. All derivatives except for the methyl derivative (1b) exhibited effective inhibitory action at low micromolar concentrations on human isoforms, but only four derivatives (1e, 1f, 1h, 1i) inhibited the bovine enzyme. The bromo derivative (1f) was found to be strongest inhibitor of all three enzymes with KI values of 0.023, 0.044 and 20.57 µM for hCA-I, hCA-II and bCA, respectively. Results of our study will make valuable contributions to carbonic anhydrase inhibition studies for further investigations since inhibitors of this enzyme are important molecules for medicinal chemistry.

Keywords: Carbonic anhydrase; inhibitor; phthalimide; sulfenimide; thiophenol.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Structures of tested compounds.
Figure 2.
Figure 2.
Activity %-[C14H8BrNO2S (µM) (1f)] regression analysis graph for hCA-I in the presence of five different concentrations.
Figure 3.
Figure 3.
Activity %-[C14H8BrNO2S (µM) (1f)] regression analysis graph for hCA-II in the presence of five different concentrations.
Figure 4.
Figure 4.
Activity %-[C14H8BrNO2S (µM) (1f)] regression analysis graph for bCA in the presence of five different concentrations.
Figure 5.
Figure 5.
The BOILED-Egg predictive model for sulfenimide derivatives. The white region is the physicochemical space of molecules with highest probability of being absorbed by the gastrointestinal tract, and the yellow region is the physicochemical space of molecules with highest probability to permeate to the brain. Yolk and white areas are not mutually exclusive.
See this image and copyright information in PMC

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