Out

2024

AVANÇOS RECENTES NA SÍNTESE DE MOLÉCULAS PARA O TRATAMENTO DA DOENÇA DE PARKINSON

RECENT ADVANCES IN THE SYNTHESIS OF MOLECULES FOR THE TREATMENT OF PARKINSON'S DISEASE

AVANÇOS RECENTES NA SÍNTESE DE MOLÉCULAS.pdf

10.56161/sci.ed.202410288C2

Pedro César de Souza

Universidade Federal de Pernambuco

Orcid ID do autor (https://orcid.org/0009-0005-8701-9103)

Thaynara Paula Warren Bezerra

Universidade Federal de Pernambuco

Orcid ID do autor (https://orcid.org/0000-0002-4000-5047)

Isabella Luiza Ralph de Oliveira

Universidade Federal de Pernambuco

Orcid ID do autor (https://orcid.org/0000-0003-2854-4272)

Maria Isabela Ferreira de Araújo

Universidade Federal de Pernambuco

Orcid ID do autor (https://orcid.org/0000-0003-0908-4661)

Michelle Melgarejo da Rosa

Universidade Federal de Pernambuco

Orcid ID do autor (https://orcid.org/0000-0002-0163-3833)

RESUMO

A Doença de Parkinson (DP) continua sendo um dos maiores desafios na neurociência moderna, com suas consequências devastadoras na vida dos pacientes. Caracterizada pela perda progressiva de neurônios dopaminérgicos e pelos sintomas motores e não motores debilitantes, a DP exige terapias que vão além do alívio sintomático. Este estudo revisa a síntese e o impacto de novas moléculas neuroprotetoras, que prometem revolucionar o tratamento da DP. Dos 40 artigos revisados, publicados entre 2020 e 2024, 12 foram selecionados a partir das bases de dados mais relevantes, como PubMed, Scopus e Web of Science. Moléculas como PA96 e derivados de benzimidazol destacaram-se por sua eficácia em modelos pré-clínicos, superando tratamentos convencionais, como a levodopa, ao não só aliviar os sintomas, mas também retardar a neurodegeneração e reduzir a neuroinflamação. Este trabalho evidencia que essas novas moléculas não apenas oferecem melhoras motoras, mas também uma proteção neuronal vital, marcando um avanço significativo para pacientes com DP. Esses compostos emergem como alternativas terapêuticas promissoras, capazes de transformar o manejo da doença e melhorar a qualidade de vida dos pacientes.

PALAVRAS-CHAVE: Química medicinal; Derivados benzimidazol; Doenças de Parkinson.

REFERÊNCIAS

Blagov A, Postnov A, Sukhorukov V, Popov M, Uzokov J, Orekhov A. Significance of Mitochondrial Dysfunction in the Pathogenesis of Parkinson's Disease. Front Biosci (Landmark Ed). 2024;29(1):36. doi:10.31083/j.fbl2901036

Cabreira, V., & Massano, J. (2019). Parkinson's Disease: Clinical Review and Update. Acta Médica Portuguesa, 32(10), 661?670. https://doi.org/10.20344/amp.11978

CHOCHKOVA, Maya et al. Synthesis, Molecular Docking, and Neuroprotective Effect of 2-Methylcinnamic Acid Amide in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).An Induced Parkinson's Disease Model. Crystals, v. 12, n. 11, p. 1518, 2022.

Church FC. Treatment Options for Motor and Non-Motor Symptoms of Parkinson's Disease. Biomolecules. 2021; 11(4):612. https://doi.org/10.3390/biom11040612

DE YEBENES, Justo Garcia. Introduction: pramipexole: a novel dopamine agonist for the treatment of Parkinson's disease. European Journal of Neurology, v. 7, 2000.

Ellis TD, Colón-Semenza C, DeAngelis TR, et al. Evidence for Early and Regular Physical Therapy and Exercise in Parkinson's Disease. Semin Neurol. 2021;41(2):189-205. doi:10.1055/s-0041-1725133

Elsworth JD. Parkinson's disease treatment: past, present, and future. J Neural Transm (Vienna). 2020;127(5):785-791. doi:10.1007/s00702-020-02167-1

Feng T, Zheng H, Zhang Z, Fan P, Yang X. Mechanism and therapeutic targets of the involvement of a novel lysosomal proton channel TMEM175 in Parkinson's disease. Ageing Res Rev. Published online July 2, 2024. doi:10.1016/j.arr.2024.102373

HAN, Y. et al. Small molecule chaperones for the treatment of Gaucher disease and GBA1-associated Parkinson disease. Journal of Molecular Biology, v. 432, p. 4671-4690, 2020. DOI: 10.1016/j.jmb.2020.05.009.

HUANG, Guang et al. Discovery of fast-acting dual-stage antimalarial agents by profiling pyridylvinylquinoline chemical space via copper catalyzed azide-alkyne cycloadditions. European journal of medicinal chemistry, v. 209, p. 112889, 2021.

Kalinderi K, Papaliagkas V, Fidani L. GLP-1 Receptor Agonists: A New Treatment in Parkinson's Disease. International Journal of Molecular Sciences. 2024; 25(7):3812. https://doi.org/10.3390/ijms25073812

KIM, S. et al. Synthesis and biological evaluation of novel quinoline derivatives as neuroprotective agents for Parkinson's disease. Bioorganic & Medicinal Chemistry Letters, v. 31, p. 5672-5679, 2021. DOI: 10.1016/j.bmcl.2020.127856.

Li Y, Yu C, Jiang X, Fu J, Sun N, Zhang D. The mechanistic view of non-coding RNAs as a regulator of inflammatory pathogenesis of Parkinson's disease. Pathol Res Pract. 2024;258:155349. doi:10.1016/j.prp.2024.155349

LI, Xin et al. Chemical conversion of nicotinamide into type I positive allosteric modulator of ?7 nAChRs. Bioorganic & Medicinal Chemistry Letters, v. 29, n. 15, p. 1928-1933, 2019.

Makarious MB, Lake J, Pitz V, et al. Large-scale rare variant burden testing in Parkinson's disease. Brain. 2023;146(11):4622-4632. doi:10.1093/brain/awad214

MATUCCI, Rosanna et al. Carbachol dimers with primary carbamate groups as homobivalent modulators of muscarinic receptors. European Journal of Pharmacology, v. 883, p. 173183, 2020.

MU?LLER, Thomas et al. Efficacy of Tolcapon on Parkinson's Disease Associated Non Motor Symptoms: The TANIMOS Study (P01. 066). 2013.

Pajares M, I. Rojo A, Manda G, Boscá L, Cuadrado A. Inflammation in Parkinson's Disease: Mechanisms and Therapeutic Implications. Cells. 2020; 9(7):1687. https://doi.org/10.3390/cells9071687

PATEL, M. et al. Synthesis and pharmacological evaluation of new thiazolidinone derivatives for Parkinson's disease. Bioorganic & Medicinal Chemistry, v. 39, p. 567-578, 2021. DOI: 10.1016/j.bmc.2020.116258.

PINDER, Roger M. Editorial Foreword: Drugs for Parkinson's disease: Levodopa is still the gold standard. Neuropsychiatric Disease and Treatment, v. 4, n. 1, p. 0, 2008.

Qi R, Sammler E, Gonzalez-Hunt CP, et al. A blood-based marker of mitochondrial DNA damage in Parkinson's disease. Sci Transl Med. 2023;15(711):eabo1557. doi:10.1126/scitranslmed.abo1557

RÍSQUEZ-CUADRO, Rocío et al. Pharmacological Chaperones for the Treatment of ?-Mannosidosis. Journal of Medicinal Chemistry, v. 62, n. 12, p. 5832-5843, 2019.

ROBINSON, Gina. Prescribing medications for Parkinson's: part two. Journal of Prescribing Practice, v. 6, n. 4, p. 166-172, 2024.

Romero-Zerbo SY, Valverde N, Claros S, et al. New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson's disease. J Adv Res. Published online February 8, 2024. doi:10.1016/j.jare.2024.01.036

ROY, Subarna et al. Design, synthesis and molecular docking studies of 5-fluoro 1-aryl/alkyl sulfonyl benzimidazole derivatives for treatment of Parkinson's disease. Phosphorus, Sulfur, and Silicon and the Related Elements, v. 198, n. 4, p. 336-344, 2023.

SAKO, Wataru et al. Comparative efficacy and safety of adjunctive drugs to levodopa for fluctuating Parkinson's disease-network meta-analysis. npj Parkinson's Disease, v. 9, n. 1, p. 143, 2023.

Santos-Rebouças CB, Cordovil Cotrin J, Dos Santos Junior GC. Exploring the interplay between metabolomics and genetics in Parkinson's disease: Insights from ongoing research and future avenues. Mech Ageing Dev. 2023;216:111875. doi:10.1016/j.mad.2023.111875

SELLBACH, A.; SILBURN, P.A. Management of Parkinson's disease. Australian Prescriber, v. 35, n. 4, p. 113-118, 2012. DOI: 10.18773/AUSTPRESCR.2012.084.

SHEN, Zhen-Bao et al. Design, synthesis, and SAR study of novel flavone 1, 2, 4-oxadiazole derivatives with anti-inflammatory activities for the treatment of Parkinson's disease. European Journal of Medicinal Chemistry, v. 255, p. 115417, 2023.

SHERIF, Salma et al. DFT and QSAR study of Catechol-O-methyltransferase (COMT) as inhibitors for Parkinson's disease treatment. Optical and Quantum Electronics, v. 56, n. 4, p. 633, 2024.

SHIRALIYEVA, R. et al. Features of drug treatment for Parkinson's disease. Milli nevrologiya jurnal?, v. 2, n. 21, p. 54-62, 2021. DOI: 10.61788/njn.v2i21.03.

STOCCHI, Fabrizio et al. Advanced Parkinson's disease treatment patterns in Italy: an observational study interim analysis. Annals of Medicine, v. 56, n. 1, p. 2315226, 2024.

Sun Q, Li YJ, Ning SB. Investigating the molecular mechanisms underlying the co-occurrence of Parkinson's disease and inflammatory bowel disease through the integration of multiple datasets. Sci Rep. 2024;14(1):17028. Published 2024 Jul 24. doi:10.1038/s41598-024-67890-1

SZÁSZ, József Attila et al. Levodopa?carbidopa?entacapone intestinal gel in advanced parkinson disease: a multicenter real-life experience. American Journal of Therapeutics, p. 10.1097, 2022.

Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021;20(5):385-397. doi:10.1016/S1474-4422(21)00030-2

VITTORIO, S. et al. Rational design of small molecules able to inhibit ?-synuclein amyloid aggregation for the treatment of Parkinson's disease. European Journal of Medicinal Chemistry, v. 192, p. 112678, 2020. DOI: 10.1016/j.ejmech.2020.112678.

WU, W. Analysis of treatment methods for Parkinson's disease. Journal of Neurological Sciences, v. 437, p. 1-8, 2023. DOI: 10.54254/2753-8818/17/20240646.

Zeng N, Wang Q, Zhang C, Zhou Y, Yan J. A review of studies on the implication of NLRP3 inflammasome for Parkinson's disease and related candidate treatment targets. Neurochem Int. 2023;170:105610. doi:10.1016/j.neuint.2023.105610

ZHAO, Y. et al. Design, synthesis, and evaluation of novel piperazine derivatives as potential therapeutic agents for Parkinson's disease. European Journal of Medicinal Chemistry, v. 188, p. 112789, 2020. DOI: 10.1016/j.ejmech.2020.112789.