Statistical Analysis of the Impact of Molecular Descriptors on Cytotoxicity of Thiourea Derivatives Incorporating 2-Aminothiazole Scaffold

Abstract

Chemical reactivity descriptors and lipophilicyty (log P) were evaluated via semi-empirical method for the quantum calculation of molecular electronic structure (PM3) in order to clarify the structure-cytotoxic activity relationships of disubstutited thioureas. Analysed compounds were obtained by the linkage of 2-aminothiazole ring, thiourea and substituted phenyl ring. The detailed examination was carried out to establish correlation between descriptors and cytotoxic activity against the MT-4 cells for 11 compounds. For the most active compounds (6 compounds) cytotoxic activity against three cancer cell lines (CCRF-CEM, WIL-2NS, CCRF-SB) and normal human cell (HaCaT) was determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release were assessed. Regression analysis revealed that electrophilicity index and chemical potential significantly contributed to expain the thioureas cytotoxic potential.

Synthesis, Structural Studies and Biological Evaluation of Connections of Thiosemicarbazide, 1,2,4-Triazole and 1,3,4-Thiadiazole with Palmitic Acid

“…There is a positive linear correlation for the QSAR models obtained of such descriptors as Rf, HF, I CC 2 , E E , E IA , μ 2 and negative linear correlation of logP 2 descriptors against biological activity for selected fungal strains. All equations presented in Table 1 satisfy the acceptability and prediction conditions of the R 2 > 0.6, Q 2 LOO > 0.6, > 0.5, R 2 − Q 2 LOO < 0.3, Q 2 (F1) , Q 2 (F2) and Q 2 (F3) > 0.6, 0.85 ≤ k ≤ 1.15 or 0.85 ≤ k ≤ 1.15, (R 2 − R 0 2 )/R 2 < 0.1 or (R 2 − R’ 0 2 )/R 2 < 0.1, > 0.5 and ∆r 2 m < 0.2 models [ 35 , 36 , 37 , 38 ]. The Figure 1 and Figure 2 show correlation between predicted and observed values for C. albicans strains characterized by the highest R 2 determination coefficients.…”

The Alleviation of Dextran Sulfate Sodium (DSS)-Induced Colitis Correlate with the logP Values of Food-Derived Electrophilic Compounds

“…A previous study suggested that there was a link between log P value of compounds and their cytotoxicity [ 43 ]. The cytotoxicity of 11 thiourea derivatives was found to be positively correlated with log P value for cancer cells and negatively correlated with log P value for HACAT normal cells [ 44 ]. In the present study, no toxic effects of FECs were observed in mice, which may be related to the low dose of the supplementation.…”

2-Methyl-6-(4-aminophenyl)-4,5-dihydro-3(2H)-pyridazinone Synthon for Some New Annelated 1,2,3-Selena/Thiadiazoles and 2H-Diazaphospholes with Anticipated Biological Activity and Quantum Chemical Calculations

“…Computational calculations were performed using density functional theory (DFT) [ 27 ] using the B3LYP (Becke three-parameter Lee–Yang–Parr) exchange-correlation functional with the base set at 6-311G (d. p). Electronic properties such as HOMO and LUMO energies were also reported and discussed in view of the results of the experimental biological activities as reported in some previous research [ 27 , 28 , 29 ]. The aim of this study is to synthesize some new derivatives of annelated 1,2,3-selena/thiadiazole and 2H-diazaphospholes and investigate the biological properties (antimicrobial and biocompatibility) of the different types of bacteria and fungi of synthesized compounds.…”