Sirakanyan Samvel N, Spinelli Domenico, Geronikaki Athina, Hakobyan Elmira K, Petrou Anti, Kartsev Victor G, Yegoryan Hasmik A, Paronikyan Ervand G, Zuppiroli Luca, Jughetsyan Hasmik V, Paronikyan Ruzanna G, Arakelyan Tatevik A, Hovakimyan Anush A
Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L. Mnjoyan 0014 Armenia
Dipartimento di Chimica G. Ciamician, Alma Mater Studiorum-Università di Bologna Via F. Selmi 2 Bologna 40126 Italy
RSC Adv. 2024 Oct 18;14(45):32922-32943. doi: 10.1039/d4ra06121g. eCollection 2024 Oct 17.
Herein, we describe the synthesis of new hybrids linked to 1,2,3- and 1,2,4-triazole units. Hybrids connected to a 1,2,3-triazole ring were synthesized using the well-known click reaction. The synthesis of the 1,2,4-triazole-based hybrids was carried out using 2-[(4-cyano-1-methyl(2-furyl)-5,6,7,8-tetrahydroisoquinolin-3-yl)oxy]acetohydrazides as starting compounds. The compounds were evaluated for their anticonvulsive activity antagonism towards pentylenetetrazole (PTZ) - and thiosemicarbazide (TSC)-induced convulsion and maximal electroshock-induced seizure (MES). Furthermore, the most active compounds were studied for their locomotory and anxiolytic activity the "open field" and elevated plus maze (EPM) assays. Finally, their antidepressant activity was studied the "forced swim" method. All the hybrids displayed pentylenetetrazole antagonism, ranging from 40% to 80%, while in the TSC model, the most active compounds increased latency of thiosemicarbazide seizures to 1.9-4.65 times compared to that of the control. Some of the tested compounds exhibited a pronounced anxiolytic and antidepressant effect. Docking study demonstrated complete agreement with experimental pharmacological data. It was revealed that the most active compounds have a pyrano[3,4-]pyridine ring in their structure.
在此，我们描述了与1,2,3 - 和1,2,4 - 三唑单元相连的新型杂化物的合成。与1,2,3 - 三唑环相连的杂化物通过著名的点击反应合成。以2 - [(4 - 氰基 - 1 - 甲基(2 - 呋喃基)-5,6,7,8 - 四氢异喹啉 - 3 - 基)氧基]乙酰肼为起始化合物进行了基于1,2,4 - 三唑的杂化物的合成。对这些化合物进行了抗惊厥活性评估，包括对戊四氮(PTZ) - 和氨基硫脲(TSC)诱导的惊厥以及最大电休克诱导的癫痫发作(MES)的拮抗作用。此外，对活性最高的化合物进行了运动和抗焦虑活性研究，采用“旷场”和高架十字迷宫(EPM)试验。最后，采用“强迫游泳”方法研究了它们的抗抑郁活性。所有杂化物均表现出40%至80%的戊四氮拮抗作用，而在TSC模型中，活性最高的化合物使氨基硫脲癫痫发作的潜伏期比对照组延长至1.9 - 4.65倍。一些受试化合物表现出明显的抗焦虑和抗抑郁作用。对接研究表明与实验药理学数据完全一致。结果表明，活性最高的化合物在其结构中含有一个吡喃并[3,4 - ]吡啶环。
