Flaherty Lab Publications
2024
40. Shrinidhi, A.; Dywer, T.S.; Scott, J.A.; Watts, V.J.; Flaherty, D.P.* Pyrazolo-Pyrimidinones with Improved Solubility and Selective Inhibition of Adenylyl Cyclase Type 1 Activity for Treatment of Inflammatory Pain. Journal of Medicinal Chemistry, 2024, 67, 18290 – 18316. https://doi.org/10.1021/acs.jmedchem.4c01645.
39. Youse, M. Y.; Abutaleb, N. S.; Nocentini, A.; Abdelsattar, A. S.; Ali, F.; Supuran, C. T.; Seleem, M. N.; Flaherty, D. P. Optimization of Ethoxzolamide Analogs with Improved Pharmacokinetic Properties for In vivo Efficacy against Neisseria gonorrhoeae. Journal of Medicinal Chemistry, 2024, Article ASAP, https://doi.org/10.1021/acs.jmedchem.4c01187.
38. Bonardi, A.; Nocentini, A.; Giovannuzzi, S.; Paoletti, N.; Ammara, A.; Bua, S.; Abutaleb, N. S.; Abdelsattar, A. S.; Capasso, C.; Gratteri, P.; Flaherty, D. P.; Seleem, M. N.; Supuran, C. T. Development of Penicillin-Based Carbonic Anhydrase Inhibitors Targeting Multidrug-Resistance Neisseria gonorrhoeae. 2024, Journal of Medicinal Chemistry, just accepted. doi: https://doi.org/10/1021/acs.jmedchem.4c00740.
37. Holly, K. J.; Kataria, A.; Flaherty, D. P.*; Groshong, A.* Unguarded liabilities: Borrelia burgdorferi’s complex amino acid dependence presents a unique target for inhibition. 2024, Frontiers in Antibiotics, 3, 1395425. doi: https://doi.org/10.3389/frabi.2024.1395425.
36. Camara, A.; Chugh, H.; George, A.; Dolidze, L.; Ryu, K.; Holly, K. J.; Flaherty, D. P.; Mattoo, S. Discovery and Validation of a Novel Inhibitor of HYPE-mediated AMPylation. 2024, Cell Stress and Chaperones. 29, 404 – 424. doi: https://doi.org/10.1016/j.cstres.2024.04.001.
35. Jena, B. C.; Flaherty, D. P.; O’Brien, V. P.; Watts, V. J. Biochemical Pharmacology of Adenylyl Cyclases in Cancer. Biochemical Pharmacology, 2024, in press. doi: https://doi.org/10.1016/j.bcp.2024.116160
34. Imhoff, R.; Patel, R.; Safdar, M. H.; Jones, H.; Pinto-Fernandez, A.; Vendrell, I.; Chen, H.; Muli, C.; Krabill, A.; Kessler, B.; Wendt, M. Das, C.; Flaherty, D. P.* Covalent Fragment Screening and Optimization Identifies Chloroacetohydrazide Scaffold as Inhibitors of Ubiquitin C-Terminal Hydrolase L1. Journal of Medicinal Chemistry, 2024, 67, 4496 - 4524. doi: https://doi.org/10.1021/acs.jmedchem.3c01661
33.Tang, H.; Gupta, A.; Morrisroe, S.; Bao, C.; Schwantes-An, T.-H.; Gupta, G.; Liang, S.; Sun, Y.; Chu, A.; Luo, A.; Elangovan, V.R.; Sangam, S.; Shi, Y.; Naidu, S.; Jheng, J.-R.; Ciftci-Yilmaz, S.; Warfel, N.; Hecker, L.; Mitra, S.; Coleman, A.; Lutz, K.; Pauciulo, M.; Lai, Y.-C.; Javaheri, A.; Dharmakumar, R.; Wu, W.-H.; Flaherty, D. P.; Karnes, J.; Breuils-Bonnet, S.; Boucherat, O.; Bonnet, S.; Yuan, J.; Jacobson, J.; Duarte, J.; Nichols, W.; Garcia, J.; Desai, A. Deficiency of the Deubiquitinase, UCHL1, Attenuates Pulmonary Hypertension. Circulation, 2024, just accepted
32. Kenny, S.; Lai, C-H.; Chiang, T-S.; Brown, K.; Hewitt, C. S.; Krabill, A. D.; Chang, H-T.; Wang, Y-S.; Flaherty, D. P.; Hsu, S-T.; Das, C. Altered protein dynamics and a more reactive catalytic cysteine in a neurodegeneration-associated UCHL1 mutant. Journal of Molecular Biology, 2024, 436, 168438. doi: https://doi.org/10.1016/j.jmb.2024.168438
2023
31. Giovannuzzi, S.; Marakpaka, A. K.; Abutaleb, N. S.; Carta, F.; Liang, H-W.; Nocentini, A.; Pisano, L.; Seleem, M. N.; Flaherty, D. P.; Supuran, C. T. Inhibition of pathogenic bacterial carbonic anhydrases by monothiocarbamates. Journal of Enzyme Inhibition and Medicinal Chemistry, 2023, 38, 2284119. doi: https://doi.org/10.1080/14756366.2023.2284119
30. Imhoff, R. D.; Rosenthal, M. R.; Ashraf, K.; Bhanot, P.; Ng, C. L.; Flaherty, D. P.* Identification of covalent fragment inhibitors for Plasmodium falciparum UCHL3 with anti-malarial efficacy. Bioorganic and Medicinal Chemistry Letters, 2023, 94, 129458, doi: https://doi.org/10.1016/j.bmcl.2023.129458
29. Young, M.; Chojnacki, M.; Blanchard, C.; Cao, X.; Johnson, W. L.; Flaherty, D. P.*; Dunman, P. D.* Genetic Determinants of Acinetobacter baumannii serum-associated adaptive efflux-mediated antibiotic resistance. Antibiotics. 2023, 12, 1173 – 1195.
28. Chilambi, G. S.; Wang, Y-H.; Wallace, N.; Obiwuma, C.; Evans, K.; Li, Y. Shalaby, M-A.; Flaherty, D. P.; Shields, R.; Doi, Y.; Van Tyne, D. Carbonic anhydrase inhibition as a target for antibiotic synergy in enterococci. Microbiology Spectrum, 2023, published online, e03963-22.
27. Abutaleb, N. S.; Shrinidhi, A.; Bandara, A. B.; Seleem, M. N.; Flaherty, D. P.* Evaluation of 1,3,4-thiadiazole carbonic anhydrase inhibitors for gut decolonization of vancomycin-resistant enterococci. ACS Medicinal Chemistry Letters, 2023, 14, 487 – 492
26. Marapaka, A. K.; Nocentini, A; Youse, M. S.; An, W.; Holly, K. J.; Das, C.; Yadav, R.; Seleem, M. N.; Supuran, C. T.; Flaherty, D. P.* Structural characterization of thiadiazolesulfonamide inhibitors bound to Neisseria gonorrhoeae a-carbonic anhydrase. ACS Medicinal Chemistry Letters, 2023, 14, 103 - 109.
2022
25. Dwyer, T.; O’Brien, J. B.; Ptak, C.; LaVigne, J. E.; Flaherty, D. P.; Watts, V. J.; Roman, D. L. Protein-protein interaction-based high throughput screening for adenylyl cyclase 1 inhibitors: design, implementation, and discovery of a novel chemotype. Frontiers Pharmacology, 2022, 13, 977742.
24. An, W.; Holly, K. J.; Nocentini, A.; Imhoff, R. D.; Hewitt, C. S.; Abutaleb, N. S.; Cao, X.; Seleem, M. N.; Supuran, C. T.; Flaherty, D. P.* Structure-activity relationship studies for inhibitors for vancomycin-resistant Enterococcus and human carbonic anhydrases. Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, 37, 1838-1844, DOI: 10.1080/14756366.2022.2092729
23. Scott, J. A.; Soto-Velasquez, M.; Hayes, M. P.; LaVigne, J. E.; Miller, H. R.; Kaur, J.; Ejendal, K. F. K.; Watts, V. J.*; Flaherty, D. P.* Optimization of a pyrimidinone series for selective inhibition of Ca2+/calmodulin-stimulated adenylyl cyclase 1 activity for treatment of chronic pain. Journal of Medicinal Chemistry, 2022, 65, 4667 - 4686. https://doi.org/10.1021/acs.jmedchem.1c01759
22. Giovannuzzi, S.; Hewitt, C. S.; Nocentini, A.; Capasso, C.; Costantino, G.; Flaherty, D. P.; Supuran, C. T. Inhibition studies of bacterial a-carbonic anhydrases with phenols. Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, 37, 666-671. https://doi.org/10.1080/14756366.2022.2038592
21. Murgia, M.V.; Sharan, S.; Kaur, J.; Austin, W.; Hagen, L.; Wu, L.; Chen, L.; Scott, J. A.; Flaherty, D. P.; Scharf, M. E.; Watts, V. J.; Hill, C. A. High-content phenotypic screening identifies novel chemistries that disrupt mosquito activity and development. Pesticide Biochemistry and Physiology, 2022, 182, 105037. https://doi.org/10.1016/j.pestbp.2022.105037
20. Hewitt, C. S.; Das, C.; Flaherty, D. P.* Rational development and characterization of a ubiquitin variant with selectivity for ubiquitin C-terminal hydrolase L3. Biomolecules, 2022, 12, 62. https://doi.org/10.3390/biom12010062
19. Giovannuzzi, S.; Hewitt, C. S.; Nocentini, A.; Capasso, C.; Flaherty, D. P.*; Supuran, C. T.* Coumarins effectively inhibit bacterial a-carbonic ahydrases. Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, 37, 333-338. https://doi.org/10.1080/14756366.2021.2012174
18. Abutaleb, N. S.; Elhassanny, A. E. M.; Nocentini, A.; Hewitt, C. S.; Elkashif, A.; Cooper, B. R.; Supuran, C. T.; Seleem, M. N.*, Flaherty, D. P.* Repurposing FDA-Approved sulfonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae. Journal of Enzyme Inhibition and Medicinal Chemistry, 2021, 37, 51-61. DOI: 10.1080/14756366.2021.1991336
17. Giovannuzzi, S.; Abutaleb, N. S.; Hewitt, C. S.; Carta, F.; Nocentini, A.; Seleem, M. N.; Flaherty, D. P.*; Supuran, C. T.* Dithiocarbamates effectively inhibit the alpha-carbonic anhydrase from Neisseria gonorrhoeae. Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, 37, 1-8. DOI: 10.1080/14756366.2021.2012174
2021
16. Flaherty, D. P.*; Seleem, M. N.; Supuran, C. T. Bacterial Carbonic Anhydrases: Underexploited antibacterial therapeutic targets. Future Medicinal Chemistry, 2021, 13, 1619 - 1622. DOI: 10.4155/fmc-2021-0207
15. Nocentini, A.; Hewitt, C. S.; Mastrolorenzo, M. D.; Flaherty, D. P.*; Supuran, C. T.* Anion inhibition studies of the alpha-carbonic anhydrase from Neisseria gonorrhoeae. Journal of Enzyme Inhibition and Medicinal Chemistry, 2021, 36, 1061 - 1066. DOI: 10.1080/14756366.2021.1929202
14. Hewitt, C.S; Abutaleb, N.S.; Elhassanny, A.E.M.; Nocentini, A.; Cao, X.; Amo, D.P.; Youse, M.S.; Holly, K.J.; Marapaka, Anil Kumar; An, W.; Kaur, J.; Krabill, A.D.; Elkashif, A.; Elgammal, Y.; Graboski, A.L.; Supuran, C.T.; Saleem, M.N.*, Flaherty, D.P.* Structure-activity relationship studies of acetazolamide-based inhibitors with activity against Neisseria gonorrhoeae. ACS Infectious Diseases, 2021, 7, 1969-1984. DOI: 10.1021/acsinfecdis.1c00055.
13. Chojnacki, M.; Cao, X.; Flaherty, D.P.* and Dunman, P.D.* Optimization of 2-acylaminocycloalkythiophene derivatives for activity against Staphylococcus aureus. Antibiotics, 2021, 10, 369
12. Krabill, A.D.; Chen, H.; Hussain, S.; Hewitt, C.S.; Imhoff, R.D.; Muli, C.S.; Das, C.; Galardy, P.J.; Wendt, M.K.; Flaherty, D.P.; Optimization and Anti-Cancer Properties of Fluoromethylketones as Covalent Inhibitors for Ubiquitin C-Terminal Hydrolase L1. Molecules, 2021, 26(5), p.1227.
11. Sheedlo, M. J.; Kenny, S.; Podkoytov, I. S.; Brown, K.; Ma, J.; Iyer, S.; Hewitt, C. S.; Arbough, T.; Mikhailovskii, O.; Flaherty D. P.; Wilson, M. A.; Skrynnikov, N. R.; Das, C. Insights into Ubiquitin Product Release in Hydrolysis Catalyzed by the Bacterial Deubiquitinase SdeA. Biochemistry,2021, just accepted, DOI:10.1021/acs.biochem.0c00760
10. Abutaleb, N. S.; Elhassanny, A. E. M.; Flaherty, D. P.; Seleem, M. N. In vitro and in vivo activities of carbonic anhydrase inhibitor, dorzolamide, against vancomycin-resistant enterococci. PeerJ, 2021, 9, e11059
9. Abutaleb, N. S.; Elkashif, A.; Flaherty, D. P.; Seleem, M. N. In vivo antibacterial activity of acetazolamide. Antimicrobial Agents and Chemotherapy, 2021, 65, e01715-20. DOI: 10.1128/AAC.01715-20
2020
8. Hewitt, C. S.; Krabill, A. D.; Das, C.; Flaherty, D. P. Development of Ubiquitin Variants with Selectivity for Ubiquitin C-Terminal Hydrolase Deubiquitinase. Biochemistry, 2020, 59 (37), 3447 – 3462
7. Kaur, J.; Cao, X.; Abutaleb, N. S.; Elkashif, A.; Graboski, A. L.; Krabill, A. D.; AbdelKhalek, A. H.; An, W.; Bhardwaj, A.; Seleem, M. N.; Flaherty, D. P. Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant Enterococcus. Journal of Medicinal Chemistry, 2020, 63(17), 9540-9562. DOI:10.1021/acs.jmedchem.0c00734.
6. Chojnacki, M.; Cao, X.; Young, M.; Fritz, R.; Dunman, P. M.; Flaherty, D. P. Optimization of 4-substituted Benzensulfonamide Scaffold to Reverse Acinetobacter baumannii Serum-Adaptive Efflux Associated Antibiotic Tolerance. ChemMedChem, 2020, 15 (18), 1731-1740. DOI: 10.1002/cmdc/202000328.
5. Saboo S.; Kestur, U.S.; Flaherty, D.P., Taylor, L.S. Congruent Release of Drug and Polymer from Amorphous Solid Dispersions: Insights into the Role of Drug-Polymer Hydrogen Bonding, Surface Crystallization, and Glass Transition. Molecular Pharmaceutics, 2020, 17(4), 1261-1275.
4. Krabill, A.D., Chen, H., Hussain, S., Feng, C., Abdullah, A., Hewitt, C.S.; Das, C., Aryal, U.K., Post, C.B., Wendt, M.K., Galardy, P.J. and Flaherty, D.P.Ubiquitin C-terminal hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor. ChemBioChem, 2020, 21, 712-722.