Transcription regulatory factor expression in T-helper cell differentiation pathway in eutopic endometrial tissue samples of women with endometriosis associated with infertility.

Endometriosis is a disease of epidemiological gravity of unknown primary reason. A complex of constitutional factors including the immune system has been considered as its background. The aim of the study was to identify Th1 and Th2 cells as well as the T-regulatory subset in the endometrium of women with endometriosis associated with infertility upon transcription factors expression. Expression of T-bet, GATA3, and Foxp3 genes was examined using a method of polymerase chain reaction (PCR) in the eutopic endometrial samples of 20 women with endometriosis associated with infertility and 20 women with infertility of tubal origin. An increase in mRNA expression for T-bet and GATA3 with prevailing mRNA level for T-bet and a decrease in Foxp3 expression were observed. In conclusion, the revealed changes in expression of transcription factors may indicate the imbalance between T-helper cells of the Th1 and Th2 type and elimination of regulatory function of T-cells, which can be one of the causes of endometriosis predisposing to the development of infertility associated with this disease.

2-Heteroaryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6 H)-thiones and Their S-Substituted Derivatives: Synthesis, Spectroscopic Data, and Biological Activity.

In the continuing search for novel, biologically effective heterocyclic agents, several methods for the synthesis of 2-heteroaryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6 H)-thiones have been developed: thiolation of oxo derivatives, [5+1] cyclocondensation of [2-(3-heteroaryl-[1,2,4]triazol-5-yl)phenyl]amines with carbon disulfide, potassium ethyl xanthogenate, or aryl isothiocyanates, and in situ reaction of 2-isothiocyanatobenzonitrile with hydrazides. A series of N-R-2-[(2-heteroaryl-[1,2,4]triazole-[1,5-c]quinazoline-5-yl)thio]acetamides were obtained by aminolysis of the corresponding acetic acids and alkylation of potassium thiolates with N-R-2-chloroacetamides. It was established that some potassium thiolates, 4 a-4 d, 4 h, and 4 i, had high antibacterial activity against Staphylococcus aureus with a minimum inhibitory concentration of 12.5 µg mL-1 and minimum bactericidal concentration of 25 µg mL-1 , which exceeded the values for trimethoprim. In addition, {2-[3-(1 H-indole-2-yl)-1 H-1,2,4-triazol-5-yl]phenyl}amine 2 i was investigated in the concentration range 100-0.01 µM at 59 lines of nine cancer cell types, and showed a mean effective concentration at 3.12-7.03 µM and cytotoxic effect at 15.56-67.38 µM. The possible mechanisms of activity were predicted by molecular docking studies to S. aureus dihydrofolate reductase and epidermal growth factor receptor kinase.

Synthesis and Antimicrobial Activity of 6-Thioxo-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]-quinazolin-2-one Derivatives.

Potassium 8-R(1)-9-R(2)-10-R(3)-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-thiolates 2.1-2.26 were synthesized via cyclocondensation of 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones 1.1-1.26 with carbon disulfide, potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2-propanol. The corresponding thiones 3.1-3.26 were obtained by treatment of 2.1-2.26 with hydrochloric acid. It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The structures of compounds were proven by a complex of physicochemical methods ((1)H, (13)C NMR, LC-MS, and EI-MS). The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25-100 µg/mL, MBC 12.5-200 µg/mL) to the synthesized compounds.