Nitric Oxide Donors and Selective Carbonic Anhydrase Inhibitors: A Dual Pharmacological Approach for the Treatment of Glaucoma, Cancer and Osteoporosis
Abstract
:1. Introduction
2. Discussion
2.1. Ocular Diseases
Compound | Structure | Ki (nM) | ||
---|---|---|---|---|
hCA I | hCA II | hCA IV | ||
Dorzolamide | 50,000 | 3.2 | 43 | |
Isosorbide mononitrate | >100,000 | >100,000 | >100,000 | |
1 | 2950 | 14 | 4360 | |
2 | 470 | 71 | 46 | |
3 | 410 | 13 | 181 | |
4 | 705 | 76 | 339 | |
5 | 1520 | 63 | 3905 | |
6 | 189 | 18 | 44 | |
7 | 242 | 198 | 345 | |
8 | 15 | 10 | 47 | |
9 | 40 | 28 | 154 | |
10 | 137 | 33 | 225 | |
11 | 32 | 10 | 46 | |
12 | 43 | 14 | 38 | |
13 | 395 | 101 | 139 | |
14 | 587 | 88 | 148 | |
15 | 41 | 12 | 76 | |
16 | 950 | 71 | 89 | |
17 | >100,000 | >100,000 | nd | |
18 | >100,000 | >100,000 | nd | |
19 | >100,000 | >100,000 | nd | |
20 | >100,000 | >100,000 | nd | |
21 | >100,000 | >100,000 | nd | |
22 | >100,000 | >100,000 | nd | |
23 | >100,000 | >100,000 | nd | |
24 | >100,000 | >100,000 | nd | |
25 | >100,000 | >100,000 | nd | |
26 | >100,000 | >100,000 | nd | |
27 | >100,000 | >100,000 | nd | |
28 | >100,000 | >100,000 | nd | |
Dichlorophenamide | 1200 | 38 | 15,000 | |
Acetazolamide | 250 | 12 | 74 |
2.2. Cancer and Metastasis
Compound | Structure | Ki (nM) | |
---|---|---|---|
hCA IX | hCA XII | ||
Dorzolamide | 36 | 3.1 | |
6 | 165 | 30 | |
7 | 253 | 147 | |
8 | 11 | 19 | |
9 | 235 | 31 | |
10 | 177 | 42 | |
11 | 10 | 31 | |
12 | 11 | 43 | |
13 | 93 | 87 | |
14 | 83 | 83 | |
15 | 25 | 29 | |
16 | 85 | 116 | |
Acetazolamide | 25 | 5.7 |
2.3. Osteoporosis
3. Biological Evaluation in vivo
Compound * | IOP Lowering Effect | ||||
---|---|---|---|---|---|
Basal IOP (mmHg) | After Carbomer (mmHg) | Post-Treatment IOP (mmHg) # | ΔΔIOP (mmHg) ** | Tmax (min) *** | |
1 | 19.8 ± 0.7 | - | 15.9 ± 0.7 | −4.7 ± 0.7 | 60 |
3 | 19.2 ± 0.5 | - | 16.5 ± 0.4 | −3.7 ± 0.3 | 120 |
6 | 18.2 ± 0.7 | 32.4 ± 1.4 | 20.6 ± 1.8 | −15.7 ± 1.8 | 60 |
Vehicle | 17.9 ± 0.3 | 32.4 ± 1.3 | 31.8 ± 1.9 | 0 ± 09 | - |
Isosorbide mononitrate | 16.8 ± 0.3 | 35.3 ± 1.2 | 28.4 ± 1.6 | −6.8 ± 0.5 | 30 |
Dorzolamide | 14.7 ± 0.9 | 35.4 ± 0.8 | 16.7 ± 0.8 | −7.4 ± 1.9 | 60 |
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Carradori, S.; Mollica, A.; De Monte, C.; Granese, A.; Supuran, C.T. Nitric Oxide Donors and Selective Carbonic Anhydrase Inhibitors: A Dual Pharmacological Approach for the Treatment of Glaucoma, Cancer and Osteoporosis. Molecules 2015, 20, 5667-5679. https://doi.org/10.3390/molecules20045667
Carradori S, Mollica A, De Monte C, Granese A, Supuran CT. Nitric Oxide Donors and Selective Carbonic Anhydrase Inhibitors: A Dual Pharmacological Approach for the Treatment of Glaucoma, Cancer and Osteoporosis. Molecules. 2015; 20(4):5667-5679. https://doi.org/10.3390/molecules20045667
Chicago/Turabian StyleCarradori, Simone, Adriano Mollica, Celeste De Monte, Arianna Granese, and Claudiu T. Supuran. 2015. "Nitric Oxide Donors and Selective Carbonic Anhydrase Inhibitors: A Dual Pharmacological Approach for the Treatment of Glaucoma, Cancer and Osteoporosis" Molecules 20, no. 4: 5667-5679. https://doi.org/10.3390/molecules20045667