SINTEZA ȘI CERCETAREA PROPRIETĂȚILOR FARMACOFORE ALE UNOR N-(DIMETILFENIL) HIDRAZINCARBOTIOAMIDE

Abstract

The present study was focused on the synthesis of some N-(dimethylphenyl)hydrazine carbothioamides 1-4, that contain the following N-substituents: 2,4-dimethylphenyl; 2,5-dimethylphenyl; 2,6-dimethylphenyl; 3,4-dimethylphenyl, to increase lipophilicity and N-(dimethylphenyl)-2-(pyridin-2-ylmethylidene)hydrazinecarbothioamides 5-8, analogous of Triapine. The structural formula of the compounds was characterized by means of spectroscopy: FT-IR, 1H-, and 13CRMN, and the molecular structure, for the first time, by means of X-ray diffraction. The study of antioxidant activity has shown that all compounds 1-8 are powerful antioxidants. N-(dimethylphenyl)-2-(pyridin2-ylmethylidene)hydrazinecarbothioamides 5-8 were tested as inhibitors of MCF-7 (breast cancer) cell proliferation. It was found that all the compounds exhibit activity comparable to that of Doxorubicin, among them the compound N-(2,5-dimethylphenyl)-2-(pyridin-2-ylmethylidene)hydrazinecarbothioamide 6, with IC50=0.8 μM/L, demonstrated the highest activity.Studiul de față a fost axat pe sinteza unor N-(dimetilfenil)hidrazincarbotioamide 1-4 cu următorii N-substituenți: 2,4-dimetilfenil; 2,5-dimetilfenil; 2,6-dimetilfenil; 3,4-dimetilfenil, pentru a mări lipofilicitatea și N-(dimetilfenil)2-(piridin-2-ilmetiliden)hidrazincarbotioamide 5-8, analogice Triapinei. Formula de structură a compușilor a fost stabilită prin intermediul spectroscopiei FT-IR, 1H-, și 13CRMN, iar structura moleculară, în premieră, prin intermediul difracției cu raze X. A fost studiată activitatea antioxidantă a tuturor compușilor sintetizați 1-8, care s-au dovedit a fi antioxidanți performanți. N-(dimetilfenil)-2-(piridin-2-ilmetiliden)hidrazincarbotioamidele 5-8 au fost testate ca inhibitori ai proliferării celulelor MCF-7 (cancerul mamar). S-a constatat că toți compușii manifestă activitate comparabilă cu cea a Doxorubicinei, dintre aceștia compusul N-(2,5-dimetilfenil)-2-(piridin-2-ilmetiliden)hidrazincarbotioamida 6, cu IC50=0,8 μM/L, a demonstrat cele mai bune rezultate.