In Silico Identification and Biological Evaluation of Antioxidant Food Components Endowed with Human Carbonic Anhydrase IX and XII Inhibition
Abstract
:1. Introduction
2. Materials and Methods
2.1. Molecular Modeling Studies
2.2. Carbonic Anhydrase Inhibition Assay
2.3. Inhibition Growth Assay
3. Results
3.1. Structure-Based Virtual Screening (SBVS)
3.2. Carbonic Anhydrase Inhibition Assay
- (i)
- As for compound 14, the data reported in Table 1 clearly showed the tumor-associated hCA XII isoform was 3.5-fold more potently inhibited when compared to the hCA IX (KIs of 0.092 and 0.32 µM, respectively) with a selectivity index (SI; KI hCA IX/KI hCA XII) of 3.5.
- (ii)
- The same kinetic profile was also recovered for 6, although enhanced enzymatic SIs were observed. The tumor-associated hCA XII resulted inhibited 27.0-fold more potently when compared to the IX (KIs of 0.096 and 2.59 µM, respectively).
- (iii)
- Compound 12 was already investigated as a potential inhibitor hCA on the widely expressed hCAs, I and II, and on the tumor-associated IX and XII from some authors of this manuscript and the data reported in Table 1 were in good agreement [28]. It is worth considering that an impressive hCA XII selective inhibition was obtained from such a substance, thus being the most potent and selective against such a tumor-associated isoform (KIs of 0.31 and 0.0048 µM for the hCA IX and XII, respectively).
3.3. Docking Pose and Thermodynamic Analysis of the Best Hits
3.4. Cell Viability Assay
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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KI (µM) * | |||||
---|---|---|---|---|---|
2D Chemical Structure | Hit | hCA I | hCA II | hCA IX | hCA XII |
6 | >100 | >100 | 2.59 | 0.096 | |
12 | >100 [28] | >100 [28] | 0.31 | 0.0048 [28] | |
14 | >100 | >100 | 0.32 | 0.092 | |
AAZ | 0.250 | 0.012 | 0.026 | 0.0057 |
hCA IX | hCA XII | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Hit | HB | SB | GC | S | C | HB | SB | GC | S | C |
6 | 3 | 0 | 179 | 0 | 0 | 4 | 0 | 222 | 0 | 0 |
12 | 8 | 0 | 167 | 1 | 0 | 7 | 2 | 291 | 0 | 1 |
14 | 3 | 0 | 224 | 0 | 0 | 4 | 0 | 222 | 0 | 0 |
hCA IX | hCA XII | ||||||||
---|---|---|---|---|---|---|---|---|---|
Hit | FooDB ID | ΔE | ΔEElec | ΔEvdW | ΔESolv | ΔE | ΔEElec | ΔEvdW | ΔESolv |
6 | FDB021188 | −37.89 | −71.80 | −17.28 | 46.18 | −43.75 | −110.89 | −25.64 | 81.26 |
12 | FDB006174 | −23.42 | −59.74 | −12.72 | 37.79 | −31.83 | −227.57 | −28.01 | 206.77 |
14 | FDB011657 | −31.22 | −36.62 | −22.44 | 26.06 | −43.81 | −105.69 | −22.33 | 73.05 |
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Costa, G.; Maruca, A.; Rocca, R.; Ambrosio, F.A.; Berrino, E.; Carta, F.; Mesiti, F.; Salatino, A.; Lanzillotta, D.; Trapasso, F.; et al. In Silico Identification and Biological Evaluation of Antioxidant Food Components Endowed with Human Carbonic Anhydrase IX and XII Inhibition. Antioxidants 2020, 9, 775. https://doi.org/10.3390/antiox9090775
Costa G, Maruca A, Rocca R, Ambrosio FA, Berrino E, Carta F, Mesiti F, Salatino A, Lanzillotta D, Trapasso F, et al. In Silico Identification and Biological Evaluation of Antioxidant Food Components Endowed with Human Carbonic Anhydrase IX and XII Inhibition. Antioxidants. 2020; 9(9):775. https://doi.org/10.3390/antiox9090775
Chicago/Turabian StyleCosta, Giosuè, Annalisa Maruca, Roberta Rocca, Francesca Alessandra Ambrosio, Emanuela Berrino, Fabrizio Carta, Francesco Mesiti, Alessandro Salatino, Delia Lanzillotta, Francesco Trapasso, and et al. 2020. "In Silico Identification and Biological Evaluation of Antioxidant Food Components Endowed with Human Carbonic Anhydrase IX and XII Inhibition" Antioxidants 9, no. 9: 775. https://doi.org/10.3390/antiox9090775