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

Abstract

Synthesis, characterization, and investigation of antiproliferative activities against human cancer cell lines (MV4-11, MCF-7, and A549) and Toxoplasma 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 using 1H and 13C 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 compounds 4a–k against normal mouse fibroblast Balb/3T3 cells is about 20–100 times lower than against cancer cell lines. According to our results, compounds 4a, 4b, 4d, and 4i have very strong activity against human breast carcinoma MCF-7, with IC50 values from 3.18 to 4.28 µg/ml. Moreover, diaminotriazines 4a–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 possible anti-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 complex formed by compound 4a and two thymine molecules are investigated using quantum mechanical methods.

Synthesis and Physicochemical Characterization of Novel Dicyclopropyl-Thiazole Compounds as Nontoxic and Promising Antifungals

“…Due to the nonlinear optical properties (NLO) of the thiazole system, it is used in optical devices such as photovoltaic detectors or light-emitting diodes [14]. However, its greatest advantage is that it exhibits a wide range of biological properties, such as antimicrobial [15][16][17][18], anticancer [19][20][21], anticonvulsant [22], antioxidant [23] and anti-SARS-CoV [24]. Numerous studies, including those carried out over the years by our group, show that thiazole derivatives have high antifungal activity [3,25].…”

The Current Directions of Searching for Antiparasitic Drugs

“…R = F, Br, Cl, CH3, CF3, OCH3, 2,4-diF, CN, N3, NO2 The same authors presented a synthesis, characterization and invest proliferative activities against human cancer cell lines and Toxoplasma go twelve novel 2,4-diaminotriazine-thiazoles (Figure 17). Similarly, as in the vious compounds, the new derivatives were characterized by a much low values 9-68 times lower) than sulfadiazine used as a reference drug [83]. The same authors presented a synthesis, characterization and investigation of antiproliferative activities against human cancer cell lines and Toxoplasma gondii parasite of twelve novel 2,4-diaminotriazine-thiazoles (Figure 17).…”

Synthesis, antimicrobial activity, and determination of the lipophilicity of ((cyclohex-3-enylmethylene)hydrazinyl)thiazole derivatives

“…The last years of the research have confirmed that thiazole scaffold has diverse biological properties that can be used to treat many diseases, such as microbial infections (Bikobo et al 2017;Secci et al 2012;Łączkowski et al 2018a, 2018bZaki et al 2018;Ansari et al 2018), Parkinson's disease (Carradori et al 2018), cancer (de Santana et al 2018;Łączkowski et al 2014, 2016a, 2016bPiechowska et al 2019;Gomha et al 2018), epilepsy (Siddiqui and Ahsan 2010;Ahangar et al 2011;Łączkowski et al 2016a, 2016b, toxoplasmosis (Schultz et al 2014;Łączkowski et al 2018a, 2018b, and antioxidants (Geronikaki et al 2013;Djukic et al 2018). Considering the above-mentioned findings, we decided to design and synthesize the structure of hybrids incorporating both the thiazole ring and the cyclohexenyl moiety.…”