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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Perspective

Natural and Synthetic Phosphodiesterase Inhibitors in 2023: an Update on the Impact on Neurological and Psychiatric Conditions

Author(s): Giovanni Ribaudo* and Alessandra Gianoncelli

Volume 24, Issue 6, 2024

Published on: 04 October, 2023

Page: [568 - 570] Pages: 3

DOI: 10.2174/0113895575267412230926055026

Price: $65

Abstract

This Perspective provides an updated overview on the involvement of phosphodiesterase (PDE) isoforms and of the corresponding inhibitors in neurological disorders, including dementia, Parkinson’s disease, multiple sclerosis, neuropsychiatric conditions and cerebral ischemia. Particular attention has been dedicated to natural and semi-synthetic compounds. Translation into the clinic of preclinical results, toxicity profile and bioavailability represent the challenging aspects in the development of PDE inhibitors. With the aim of providing the latest updates to the reader, the 2023 contributions in the field were considered for the preparation of this Perspective.

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Graphical Abstract

[1]
Sadeghi, M.A.; Nassireslami, E.; Yousefi Zoshk, M.; Hosseini, Y.; Abbasian, K.; Chamanara, M. Phosphodiesterase inhibitors in psychiatric disorders. Psychopharmacology, 2023, 240, 1201-1219.
[http://dx.doi.org/10.1007/s00213-023-06361-3]
[2]
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[3]
Gomaa, A.A.; Farghaly, H.S.M.; Ahmed, A.M. Hemida, FK Intermittent treatment with Apremilast, a phosphodiesterase-4 inhibitor, ameliora-tes Alzheimer’s-like pathology and symptoms through multiple targeting actions in aged T2D rats. Int. Immunopharmacol., 2023, 117, 109927.
[http://dx.doi.org/10.1016/j.intimp.2023.109927]
[4]
Wang, Y.Z.; Wang, Y.L.; Che, H.J.; Jia, Y.H.; Wang, H.F.; Zuo, L.F.; Sappanone, A. A natural PDE4 inhibitor with dual anti-inflammatory and anti-oxidant activities from the heartwood of Caesalpinia sappan L. J. Ethnopharmacol., 2023, 304, 116020.
[http://dx.doi.org/10.1016/j.jep.2022.116020]
[5]
Nguyen, T.H.; Wang, S-L.; Nguyen, V.B. Microorganism-derived molecules as enzyme inhibitors to target alzheimer’s diseases pathways. Pharmaceuticals., 2023, 16(4), 580.
[6]
Liu, Z.; Li, A.; Ali, T.; He, K.; Gao, R. He, L Neuronal lack of PDE7a disrupted working memory, spatial learning, and memory but facilita-ted cued fear memory in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2023, 120, 110655.
[http://dx.doi.org/10.1016/j.pnpbp.2022.110655]
[7]
Huang, J-X.; Zhu, B-L.; Xu, J-P.; Zhou, Z-Z. Advances in the development of phosphodiesterase 7 inhibitors. Eur. J. Med. Chem., 2023, 250, 115194.
[http://dx.doi.org/10.1016/j.ejmech.2023.115194]
[8]
Justo, A.F.O.; Toscano, E.C.B.; Farias-Itao, D.S.; Suemoto, C.K. The action of phosphodiesterase-5 inhibitors on β-amyloid pathology and cognition in experimental Alzheimer’s disease: A systematic review. Life Sci., 2023, 320, 121570.
[http://dx.doi.org/10.1016/j.lfs.2023.121570] [PMID: 36921685]
[9]
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[PMID: 36173073]
[10]
Kobayashi, A.; Nakajima, M.; Noguchi, Y.; Morikawa, R.; Matsuo, Y.; Takasu, M. Molecular dynamics simulation of the complex of PDE5 and evodiamine. Life, 2023, 13(2), 578.
[http://dx.doi.org/10.3390/life13020578]
[11]
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[http://dx.doi.org/10.1186/s12868-023-00790-8]
[12]
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[13]
Roy, D.; Balasubramanian, S.; Krishnamurthy, P.T.; Sola, P.; Rymbai, E. Phosphodiesterase-4 inhibition in Parkinson’s disease: Molecular insights and therapeutic potential. Cell. Mol. Neurobiol., 2023, 43(6), 2713-2741.
[14]
Essam, R.M. Kandil, EA p-CREB and p-DARPP-32 orchestrating the modulatory role of cAMP/PKA signaling pathway enhanced by Ro-flumilast in rotenone-induced Parkinson’s disease in rats. Chem. Biol. Interact., 2023, 372, 110366.
[15]
Wei, X.; Yu, G.; Shen, H.; Luo, Y.; Shang, T. Shen, R Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement. Bioorg. Chem., 2023, 130, 106278.
[http://dx.doi.org/10.1016/j.bioorg.2022.106278]
[16]
Sharifian, A.; Varshosaz, J.; Aliomrani, M.; Kazemi, M. Nose to brain delivery of Ibudilast micelles for treatment of multiple sclerosis in an experimental autoimmune encephalomyelitis animal model. Int. J. Pharm., 2023, 638, 122936.
[http://dx.doi.org/10.1016/j.ijpharm.2023.122936]
[17]
Ashrafi, S.; Alam, S.; Sultana, A.; Raj, A.; Emon, N.U.; Richi, F.T. Papaverine: A miraculous alkaloid from opium and its multimedicinal appli-cation. Molecules, 2023, 28(7), 3149.
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[18]
Bonato, J.M.; De Mattos, B.A.; Oliveira, D.V.; Milani, H.; Prickaerts, J.; De Oliveira, R.M.W. Blood-brain barrier rescue by roflumilast after tran-sient global cerebral ischemia in rats. Neurotox. Res., 2023, 41(4), 311-323.
[http://dx.doi.org/10.1007/s12640-023-00639-2]

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