PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes

Article


Jian, J., Mazzacuva, F., Crocetti, L., Giovannoni, M. P. and Cilibrizzi, A. 2023. PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes. International Journal of Molecular Sciences. 24 (14), p. 11518. https://doi.org/10.3390/ijms241411518
AuthorsJian, J., Mazzacuva, F., Crocetti, L., Giovannoni, M. P. and Cilibrizzi, A.
Abstract

Cyclic nucleotide phosphodiesterases 4 (PDE4) are a family of enzymes which specifically promote the hydrolysis and degradation of cAMP. The inhibition of PDE4 enzymes has been widely investigated as a possible alternative strategy for the treatment of a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma, as well as psoriasis and other autoimmune disorders. In this context, the identification of new molecules as PDE4 inhibitors continues to be an active field of investigation within drug discovery. This review summarizes the medicinal chemistry journey in the design and development of effective PDE4 inhibitors, analyzed through chemical classes and taking into consideration structural aspects and binding properties, as well as inhibitory efficacy, PDE4 selectivity and the potential as therapeutic agents.

JournalInternational Journal of Molecular Sciences
Journal citation24 (14), p. 11518
ISSN1422-0067
Year2023
PublisherMDPI
Publisher's version
License
File Access Level
Anyone
Digital Object Identifier (DOI)https://doi.org/10.3390/ijms241411518
Publication dates
Online15 Jul 2023
Publication process dates
Accepted13 Jul 2023
Deposited22 Feb 2024
Copyright holder© 2023, The Authors
Permalink -

https://repository.uel.ac.uk/item/8x548

Download files


Publisher's version
ijms-24-11518-with-cover.pdf
License: CC BY 4.0
File access level: Anyone

  • 73
    total views
  • 31
    total downloads
  • 6
    views this month
  • 2
    downloads this month

Export as

Related outputs

Optimization of 4-amino-pyridazin-3(2H)-one as a valid core scaffold for FABP4 inhibitors
Floresta, G., Crocetti, L., Rodrigues de Oliveria Silva, R., Patamia, V., Mazzacuva, F., Chen, Y. C. S., Vergelli, C. and Cilibrizzi, A. 2023. Optimization of 4-amino-pyridazin-3(2H)-one as a valid core scaffold for FABP4 inhibitors. Archiv der Pharmazie. 356 (10), p. 2300314. https://doi.org/10.1002/ardp.202300314
Evaluating thermogravimetric analysis for the measurement of drug loading in mesoporous silica nanoparticles (MSNs)
Almaghrabi, M., Alqurshi, A., Jadhav, S. A., Mazzacuva, F., Cilibrizzi, A., Raimi-Abraham, B. and Royall, P. G. 2023. Evaluating thermogravimetric analysis for the measurement of drug loading in mesoporous silica nanoparticles (MSNs). Thermochimica Acta. 730 (Art. 179616). https://doi.org/10.1016/j.tca.2023.179616
OCT2013, an ischaemia-activated antiarrhythmic prodrug, devoid of the systemic side effects of lidocaine
Hesketh, L. M., Sikkel, M. B., Mahoney-Sanchez, L., Mazzacuva, F., Chowdury, R. A., Tzortzis, K. N., Firth, J., MacLeod, K. T., Ogrodzinski, S., Wilder, C. D. E., Pattersone, L. H., Peters, N. S. and Curtis, M. J. 2022. OCT2013, an ischaemia-activated antiarrhythmic prodrug, devoid of the systemic side effects of lidocaine. British Journal of Pharmacology. 179 (9), pp. 2037-2053. https://doi.org/10.1111/bph.15764
The surfactant co-formulant POEA in the glyphosate-based herbicide RangerPro but not glyphosate alone causes necrosis in Caco-2 and HepG2 human cell lines and ER stress in the ToxTracker assay
Mesnage, R., Gerguson, S., Brandsma, I., Moelijker, N., Zhang, G., Mazzacuva, F., Caldwell, A., Halket, J. and Antoniou, M. N. 2022. The surfactant co-formulant POEA in the glyphosate-based herbicide RangerPro but not glyphosate alone causes necrosis in Caco-2 and HepG2 human cell lines and ER stress in the ToxTracker assay. Food and Chemical Toxicology. 168 (Art. 113380). https://doi.org/10.1016/j.fct.2022.113380
Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition
Crocetti, L., Floresta, G., Zagni, C., Merugu, D., Mazzacuva, F., Rodrigues de Oliveira Silva, R., Vergelli, C., Giovannoni, M. P. and Cilibrizzi, A. 2022. Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition. Pharmaceuticals. 15 (11), p. 1335. https://doi.org/10.3390/ph15111335
Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation
Khalil, Y., Carrino, S., Lin, F., Ferlin, A., Lad, H. V., Mazzacuva, F., Falcone, S., Rivers, N., Banks, G., Concas, D., Aguilar, C., Haynes, A. R., Blease, A., Nicol, T., Al-Shawi, R., Heywood, W., Potter, P., Mills, K., Gale, D. P. and Clayton, P. T. 2022. Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation. International Journal of Molecular Sciences. 23 (Art. 987). https://doi.org/10.3390/ijms23020987
Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats
Mesnage, R., Teixeira, M., Mandrioli, D., Falcioni, L., Zwittink, D., Mazzacuva, F., Caldwell, A., Halket, J., Amiel, C., Panoff, J-M., Belpoggi, F. and Antoniou, M. N. 2021. Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats. Environmental Health Perspectives. 129 (1). https://doi.org/10.1289/EHP6990
Urinary excretion of herbicide co-formulants after oral exposure to roundup MON 52276 in rats
Mesnage, R., Mazzacuva, F., Caldwell, A., Halket, J. and Antoniou, M. N. 2021. Urinary excretion of herbicide co-formulants after oral exposure to roundup MON 52276 in rats. International Journal of Environmental Research and Public Health. 197 (Art. 111103). https://doi.org/10.1016/j.envres.2021.111103