EXPERIMENTAL:
Synthetic DetailsMethods and Materials: All reagents from commercial sources were used without further purification.Reactions were carried out under nitrogen atmosphere. Solvents were dried and purified using standard techniques. Flash chromatography was performed with analytical-grade solvents using Silicycle Silica Flash P60 (particle size 40-63 µm, 60 Å, 230 -400 mesh) silica gel. Flexible plates PE SilG/UV 250µm from Whatman ® were used for TLC. Compounds were detected by UV irradiation or staining with I 2 , unless otherwise stated. All compounds were characterized by 1 H NMR (400 MHz) and 13 C NMR ( 100MHz) on a Bruker Avance III Ultrashielded 400 Plus instrument and acquired at room temperature.
In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid per-
O6-alkylguanine-DNA alkyltransferase (AGT) repairs O6-methylguanine (O6mG) in DNA that is known to cause mutation and cancer. On the basis of calculations performed using density functional theory involving the active site of AGT, a mechanism for catalytic demethylation of O6mG to guanine has been proposed. In this mechanism, roles of six amino acids, i.e., Cys145, His146, Glu172, Tyr114, Lys165, and Ser159 in catalytic demethylation of O6mG are involved. This mechanism has three steps as follows. At the first step, Cys145 in the Cys145-water-His146-Glu172 tetrad is converted to cysteine thiolate anion while at the second step, abstraction of the Tyr114 proton by the N3 site of O6mG occurs in a barrierless manner. In the third step, abstraction of Lys165 proton by deprotonated Tyr114 and transfer of the methyl group of O6mG to the thiolate group of Cys145 anion occur simultaneously. As AGT is a major target in cancer therapy, identification of the roles of the different amino acids in demethylation of O6mG is expected to be useful in designing efficient AGT inhibitors.
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