Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells

A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.

EFFICIENCY AND COMPARISON OF THE TEST-DAY MODEL AND BLUP METHOD MODIFICATIONS FOR ASSESSING BULLS BREEDING VALUE IN SIMMENTAL CATTLE BREED

Целью проведенных исследований являлась отработка и адаптация применения методик BLUP AM (Animal Model — модель животного) и TDM (Test-Day Model — модель тестового дня) для прогнозирования племенной ценности быков-производителей и оценки селекционно-генетических параметров на популяции скота симментальской породы четырех регионов РФ. Проведен сравнительный анализ указанных методов с более ранним методом BLUP SM (Sire Model — модель отца). Рассчитана племенная ценность быков и коров симментальской породы по признакам молочной продуктивности: удой за 305 дней, выход молочного жира, выход молочного белка. Анализ полученных средних значений достоверности оценок быков-производителей, рассчитанных на основе сопоставляемых методов, свидетельствует, что достоверность для признака «удой за 305 дней» при переходе от метода SM1 к AM1 увеличивается на 2,4%, а при переходе от SM1 к TDM1 — на 7,8%. Даны варианты генетического тренда по удою с использованием различных уравнений моделей расчета племенной ценности. На основании полученных данных можно сделать вывод о том, что модель тестового дня позволяет не только повысить точность оценок быков, но и более рельефно выявить их ранги, а также несколько уменьшить срок получения достоверных оценок производителей по качеству потомства по продуктивным признакам. The purpose of this research was to develop and adapt the application of BLUP AM (Animal Model) and TDM (Test-Day Model) methods for predicting the sires breeding value and evaluating genetic parameters for Simmental cattle population in four regions of the Russian Federation. A comparative analysis of these methods with the earlier BLUP SM (Sire Model) method is performed. The breeding value for sires and cows of Simmental breed was calculated by milk production traits: milk yield for 305 days; milk fatyield; milk proteinyield. The sires reliability of average breeding value calculated by different methods reveal that milk yield for 305 days when switching from the SM1 to AM1 method increases by 2.4%, and when switching from SM1 to TDM1 — by 7.8%.The variants of the genetic trend for milk yield are given using various equations of BLUP and TDM. Based on the obtained data, it can be concluded that the Test-Day model allows increasing the accuracy of bull’s evaluation and also more clearly identifying their ranks, as well as slightly reducing the time for obtaining reliable estimates of bulls by offspring for production traits.

CUBANE HEAT OF FORMATION: CALCULATION METHODS

A comparative analysis of the enthalpies of formation of a cubane calculated by the methods of molecular mechanics and quantum chemistry is carried out. A correlation between the experimental and calculated AM1-method values of the heats of formation of frame hydrocarbons was established, which allowed us to correct the results of calculating the heat of formation of the cubane and reduce the discrepancy with the experimental value of its formation enthalpy to 10.7 kJ / mol.

Comparative Studies of Infrared Spectral Simulation of Some Benzoyl Derivatives of N-Heterocyclic Compounds Using Semi-Empirical Methods

Simulation studies based on ab initio, semi-empirical or density functional (DFT) calculations are now becoming common among the researchers who are pursuing their intereset in theoretical chemistry. These studies are based on quantum chemical softwares. These studies provide better insight for the structural and other parameters of the compounds. The present paper includes the studies on synthesis or procurement along with the simulated IR spectra of some benzoyl derivatives of N-heterocyclic compounds viz. 2-aminopyridine, 4-aminoantipyrine, 2-aminopyrimidine or 3-aminopyridine using four different AM1, PM3, MNDO and ZINDO1 semi-empirical methods. Among the methods used for the study, AM1 method is more reliable and more accurate so far as the prediction of spectral results is concerned.

Theoretical Prediction of Possible Drug Treatment of COVID-19 using Coumarins Containing Chloroquine Moeity

Chloroquine was theoretically reacted with the coumarin compound. Two compounds viz. [N-(7-chloroquinolin-4-yl)-N-(5-(diethylamino)-pentan-2-yl)-4-methyl-2-oxo-2H-chromene-7- sulfonamide] (3) and [N-(7-chloroquinolin-4-yl)-N-(5-(diethylamino)pentan-2-yl)-4-methyl-2-oxo- 2H-chromene-6-sulfonamide] (4) were suggested. The results showed that compound 4 may influence the COVID-19 treatment. The physico-chemical parameters were determined through theoretical calculations by using Hartree-Fock at different basis sets (6-31G), (STO/3G) and the semi-empirical (AM1) method. The calculations demonstrated the scheme of reaction between coumarin and the chloroquine structure by using the predicted mechanisms. The physical and chemical properties of the predicted compounds were determined to select the optimal form as the candidate for COVID-19 treatment. Compound 4 was more stable than compound 3, with different proteins viz. 6YHU, 6YI3 and 6LU7. Three types of software, including Gaussian 03, Chem-Bio office and molecular operating environment (MOE) were employed.

Theoretical study of the potential energy surface of N-formyl-L-cysteine-amide by using a genetic algorithm multi niche crowding

The generation of molecular structures constituting the conformational space of trans-N-For-L-Cys-NH2 was accomplished using the genetic algorithm MNC coupled to the semi-empirical AM1 method, AM1/GA-MNC. The structural and energy analysis of the obtained conformational space E=E(,ψ) locates 7 regions or minima ɣL, ɣD, L, D, L, ɛD and ɛL. The combination of these folds to structuring modes adopted by the side chain CH2-SH has allowed us to identify 27 stable geometric structures. The regions corresponding to helical folds αD and αL are not favorable for the system that is the subject of current study.