Synthesis, molecular docking, ctDNA interaction, DFT calculation and evaluation of antiproliferative and anti- Toxoplasma gondii activities of 2,4-diaminotriazine-thiazole derivatives

AbstractSynthesis, characterization, and investigation of antiproliferative activities against human cancer cell lines (MV4-11, MCF-7, and A549) andToxoplasma gondii parasite of twelve novel 2,4-diaminotriazine-thiazoles are presented. The toxicity of the compounds was studied at three different cell types, normal mouse fibroblast (Balb/3T3), mouse fibroblast (L929), and human VERO cells. The structures of novel compounds were determined using1H and13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives,4a–k showed very high activity against MV4-11 cell line with IC50 values between 1.13 and 3.21  µg/ml. Additionally, the cytotoxic activity of compounds4a–k against normal mouse fibroblast Balb/3T3 cells is about 20 –100 times lower than against cancer cell lines. According to our results, compounds4a,4b,4d, and4i have very strong activity against human breast carcinoma MCF-7, with IC50 values from 3.18 to 4.28  µg/ml. Moreover, diaminotriazines4a–l showed significant anti-Toxoplasma gondii activity, with IC50 values 9 –68 times lower than those observed for sulfadiazine. Molecular docking studies indicated DNA-binding site of hTopoI and hTopoII as possible anticancer targets and purine nucleoside phosphorylase as possibleanti-toxoplasmosis target. Our UV –Vis spectroscopic results indicate also that diaminotriazine-thiazoles tends to interact with DNA by intercalation. Additionally, the structure and the interaction and binding energies of a model ...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research