1,307
Views
9
CrossRef citations to date
0
Altmetric
Brief Report

Toxicity evaluation of sulfamides and coumarins that efficiently inhibit human carbonic anhydrases

, , , , ORCID Icon, ORCID Icon & ORCID Icon show all
Pages 1765-1772 | Received 03 Aug 2020, Accepted 06 Sep 2020, Published online: 17 Sep 2020

Figures & data

Figure 1. Chemical structures of compounds 1–9Citation26,Citation28.

Figure 1. Chemical structures of compounds 1–9Citation26,Citation28.

Table 1. Inhibition data of human CA isoforms hCA I, II, IV, VII, IX, and XII with the derivatives reported here and the standard sulphonamide inhibitor acetazolamide (AAZ) by a stopped-flow CO2 hydrase assayCitation30.

Figure 2. The LC50 values of the tested compounds. The upper part of the figure (compounds 14) shows the LC50 values for the four coumarins, and the lower part (compounds 59) shows the LC50 values for the sulfamides. The LC50 doses for the compounds were determined based on 50% mortality of the larvae at the end of 5 days after exposure of the embryos to different concentrations of any tested compound. LC50 doses were determined after three independent experiments with similar experimental conditions were performed (for each compound, n = 90).

Figure 2. The LC50 values of the tested compounds. The upper part of the figure (compounds 1–4) shows the LC50 values for the four coumarins, and the lower part (compounds 5–9) shows the LC50 values for the sulfamides. The LC50 doses for the compounds were determined based on 50% mortality of the larvae at the end of 5 days after exposure of the embryos to different concentrations of any tested compound. LC50 doses were determined after three independent experiments with similar experimental conditions were performed (for each compound, n = 90).

Figure 3. Images of zebrafish larvae in the control and coumarin/sulfamide derivative-treated groups. Representative images of 5 dpf zebrafish larvae exposed to different concentrations of CAIs 1–9 that are considered safe (below the LC50). No morphological changes were observed except for with compound 4, which showed a defect in swim bladder development (white arrow). Images of the control group larvae (not treated with inhibitor) and 1% DMSO-treated larvae showed normal development.

Figure 3. Images of zebrafish larvae in the control and coumarin/sulfamide derivative-treated groups. Representative images of 5 dpf zebrafish larvae exposed to different concentrations of CAIs 1–9 that are considered safe (below the LC50). No morphological changes were observed except for with compound 4, which showed a defect in swim bladder development (white arrow). Images of the control group larvae (not treated with inhibitor) and 1% DMSO-treated larvae showed normal development.

Table 2. Effects of CA inhibitors on the phenotypic parameters of 5 dpf zebrafish larvaea.

Figure 4. Histochemical analysis of coumarin- and sulfamide-treated 5 dpf zebrafish larvae. The images presented here are from the larvae treated with concentrations that showed no phenotypic defects (the concentration is shown in the top right corner of each image). The images presented here were selected from three independent groups of experiments. The H&E stained sections show no histomorphological abnormalities in the tissues of zebrafish larvae at the end of 5 days of exposure.

Figure 4. Histochemical analysis of coumarin- and sulfamide-treated 5 dpf zebrafish larvae. The images presented here are from the larvae treated with concentrations that showed no phenotypic defects (the concentration is shown in the top right corner of each image). The images presented here were selected from three independent groups of experiments. The H&E stained sections show no histomorphological abnormalities in the tissues of zebrafish larvae at the end of 5 days of exposure.