1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences 2. Institute of Physiologically Active Compounds Russian Academy of Sciences 3. Innovative Technological Center “Biologically Active Compounds and their Applications”
Abstract: Among 3-(2-aminopropyl)-1,2,4-thiadiazole derivatives contatining substitution-ready secondary amino group and exhibiting cytotoxic towards rat C 6 glioma cells three compounds with LD 50 values ranged from 6 to 48 мM were chosen. For these compounds amides with docosahexaenoic acid were synthetised and their cytotoxic activity was studied. It was shown that, although docosahexaenoic acid itself was not toxic for C 6 glioma cells, its addition to the amino derivatives of 1,2,4-thiadiazole increased or decreased resultant cytotoxicity. The effect depended on the structure of 1,2,4-thiadiazole substituents. The obtained data show that the acylation of cytotoxic compounds with docosahexaenoic acid does not necessarily lead to the increase of their activity, but sometimes can inactivate a compound. This fact should be taken into account, especially in the case of anti-cancer drug development.
Reference: Akimov M.G., Gretskaya N.M., Karnoukhova V.A., Serkov I.V., Proshin A.N., Shtratnikova V.Yu., Bezuglov V.V., The influence of docosahexaenoic acid moiety on cytotoxic activity of 1,2,4-thiadiazole derivatives, Biomeditsinskaya khimiya, 2014, vol: