20.500.12556/RUL-146363 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 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. amantadine 2-methylcinnamic acid single crystal X-ray diffraction Parkinson's disease amantadin 2-metilcimetna kislina rentgenska difrakcija monokristalov Parkinsonova bolezen true false true Angleški jezik Slovenski jezik Članek v reviji 2023-05-25 08:49:00 2023-05-25 08:49:01 2023-05-26 03:44:45 0000-00-00 00:00:00 2022 0 0 12 str. iss. 11, art. 1518 Vol. 12 Nov. 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2022-11-01 547.586.5:616.858 2073-4352 10.3390/cryst12111518 153342979 crystals-12-01518.pdf crystals-12-01518.pdf 1 BE7EC0F265881EFE85A4D623F94E489A ad08c62316071a8579d1814fc9d3001b624d469cba441e5f6ffd0ec54f44e7a7 be9a7bb5-fac8-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=169535 https://www.mdpi.com/2073-4352/12/11/1518 1 f391e004-fac7-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=169534 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0