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

• DOI: 10.1007/s00044-018-2136-6
• Publication Date: 2018-02-06T08:05:22Z
• Authors: Krzysztof Z. Łącz...; Joanna Anusiak; Marta Świtalska; Katarzyna Dzitko; Joanna Cytarska; Angelika Baranows...; Tomasz Plech; Agata Paneth; Joanna Wietrzyk; Joanna Białczyk
• Keywords: Thiazole; Docking (animal); IC50

Synthesis, characterization, and investigation of antiproliferative activities against human cancer cell lines (MV4-11, MCF-7, A549) Toxoplasma gondii parasite twelve novel 2,4-diaminotriazine-thiazoles are presented. The toxicity the compounds was studied at three different types, normal mouse fibroblast (Balb/3T3), (L929), VERO cells. structures were determined using 1H 13C NMR, FAB(+)-MS, elemental analyses. Among derivatives, 4a-k showed very high activity MV4-11 line with IC50 values between 1.13 3.21 µg/ml. Additionally, cytotoxic Balb/3T3 cells is about 20-100 times lower than lines. According to our results, 4a, 4b, 4d, 4i have strong breast carcinoma from 3.18 4.28 Moreover, diaminotriazines 4a-l significant anti-Toxoplasma activity, 9-68 those observed for sulfadiazine. Molecular docking studies indicated DNA-binding site hTopoI hTopoII as possible anticancer targets purine nucleoside phosphorylase anti-toxoplasmosis target. Our UV-Vis spectroscopic results indicate also that diaminotriazine-thiazoles tends interact DNA by intercalation. structure interaction binding energies a model complex formed compound 4a two thymine molecules investigated quantum mechanical methods.