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

Chochkova, Maya (author), Rusew, Rusi (author), Kalfin, Reni (author), Tancheva, Lyubka (author), Lazarova, Maria (author), Sbirkova-Dimitrova, Hristina (author), Popatanasov, Andrey (author), Tasheva, Krasimira (author), Shivachev, Boris (author), Petek, Nejc (author), Štícha, Martin (author)

Parkinson’s disease (PD) has emerged as the second most common form of human neurodegenerative disorders. However, due to the severe side effects of the current antiparkinsonian drugs, the design of novel and safe compounds is a hot topic amongst the medicinal chemistry community. Herein, a convenient peptide method, TBTU (O-(benzotriazole-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate), was used for the synthesis of the amide (E)-N-(2-methylcinnamoyl)-amantadine (CA(2-Me)-Am; 3)) derived from amantadine and 2-methylcinnamic acid. The obtained hybrid was studied for its antiparkinsonian activity in an experimental model of PD induced by MPTP. Mice (C57BL/6,male, 8 weeks old) were divided into four groups as follows: (1) the control, treated with normal saline (i.p.) for 12 consecutive days; (2) MPTP (30 mg/kg/day, i.p.), applied daily for 5 consecutive days; (3) MPTP + CA(2-Me)-Am, applied for 12 consecutive days, 5 days simultaneously with MPTP and 7 days after MPTP; (4) CA(2-Me)-Am +oleanoic acid (OA), applied daily for 12 consecutive days. Neurobehavioral parameters in all experimental groups of mice were evaluated by rotarod test and passive avoidance test. Our experimental data showed that CA(2-Me)-Am in parkinsonian mice significantly restored memory performance, while neuromuscular coordination approached the control level, indicating the ameliorating effects of the new compound. In conclusion, the newly synthesized hybrid might be a promising agent for treating motor disturbances and cognitive impairment in experimental PD.

• Language: English
• Keywords: amantadine, 2-methylcinnamic acid, single crystal X-ray diffraction, Parkinson's disease
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Publication date: 01.11.2022
• Year: 2022
• Number of pages: 12 str.
• Numbering: Vol. 12, iss. 11, art. 1518
• PID: 20.500.12556/RUL-146363
• UDC: 547.586.5:616.858
• ISSN on article: 2073-4352
• DOI: 10.3390/cryst12111518
• COBISS.SI-ID: 153342979
• Publication date in RUL: 25.05.2023

Record is a part of a journal

• Title: Crystals
• Shortened title: Crystals
• Publisher: MDPI
• ISSN: 2073-4352
• COBISS.SI-ID: 36677893

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: amantadin, 2-metilcimetna kislina, rentgenska difrakcija monokristalov, Parkinsonova bolezen

Projects

• Funder: Other - Other funder or multiple funders
• Project number: KP-06-Russia/7-2019