Synthesis and Structure Elucidation of Two Essential Metal Complexes: In-Vitro Studies of Their BSA/HSA-Binding Properties, Docking Simulations, and Anticancer Activities.

Imidazole and tetrazole derivatives are widely used as clinical drugs since they possess a variety of pharmaceutical function. Zinc and iron are essential trace elements of the human body, with less toxicity and good biocompatibility. In this paper, two new essential metal mononuclear complexes [M(H2tmidc)2(H2O)2]·2H2O (M = Zn (1), Fe (2)) were synthesized through the reaction of 2-((1H-tetrazol-1-yl)methylene)-1H-imidazole-4,5-dicarboxylic acid (H3tmidc) and ZnSO4·7H2O or FeSO4·7H2O. The crystal structures were determined by means of the X-ray single crystal diffraction technique. Results from fluorescence investigations show that both complexes could interact with BSA as well as HSA through the static quenching mechanism. van der Waals forces and hydrogen bonds play important roles in the interaction of complexes and BSA/HSA since both ΔH and ΔS values are negative. The results of molecular docking are consistent with those in experimental studies. Furthermore, the anticancer activity of H3tmidc and both complexes against Eca-109 were preliminarily evaluated and the results show that both complexes have better anticancer activity than the corresponding ligand H3tmidc.

[Is insulin resistance a common pathway for hereditary and environmental factors-induced hypertension?].

OBJECTIVE: To investigate whether insulin resistance is the common route for hereditary and environmental factors to cause hypertension. METHODS: 93 hypertensives with family history of hypertension, 94 hypertensives without family history of hypertension and 99 normal tensives without family history of hypertension as well as their spouse, and one child in each family were enrolled in the present study. Insulin sensitivity was calculated from fasting plasma glucose (FPG) and insulin (FINS) with the formula insulin sensitivity index (ISI) = 1/(FPG x FINS) and insulin resistance index (Homa-IR) = (FPG x FINS)/22.5. The contribution of insulin resistance to blood pressure elevation was investigated by multivariate regression analysis. RESULTS: Subjects with essential hypertension, regardless of the presence or absence of family history of hypertension, were more insulin resistant. Multivariate regression analysis demonstrated that insulin resistance contributed to 17% of mean blood pressure (MBP) elevation, whereas taken FPG + total cholesterol (TC) + high density lipoprotein (HDL) together it explained only 9% of MBP changes in the indicator group. When family history of hypertension was included as a independent variable in the analysis, it became the most important factor instead of insulin resistance in the model and contributed to 30% of the changes of MBP, while contribution of insulin resistance was significantly reduced as to explain only 7% of the changes of MBP. CONCLUSIONS: Insulin resistance is a common route for hereditary and environmental factors to induce hypertension. It is suggested that improving insulin sensitivity may play an important role in the management of essential hypertension.

[Association between G-protein beta3 subunit (GNB(3)) gene C825T polymorphism, hypertension, insulin resistance and obesity].

OBJECTIVES: To investigate the relationship between G-protein beta(3) subunit (GNB(3)) gene polymorphism and essential hypertension, insulin resistance and obesity. METHODS: Fasting plasma glucose (FPG), fasting insulin (Ins), lipid profile, and fibrinogen (Fib) were determined by convenient methods and the polymorphism of GNB(3) was detected by PCR-RFLP and sequencing in 376 individuals 187 first generation offsprings of hypertensives and 189 first generation offsprings of nonhypertensives in Daqing, China. The relationship between GNB(3) polymorphism and hypertension, insulin resistance was analyzed by univariate correlation analysis, and multivariate regression analysis with SAS software package. RESULTS: (1) The frequency of CT/TT genotype of GNB(3) C825T was significantly higher in the first generation offsprings of the hypertensives than in the first generation offsprings of nonhypertensives (0.78:0.69, P = 0.06). (2) The insulin sensitivity index [IAI = 1/(FPG x FINS)] in the CT and TT genotype groups was significantly lower than that in the group with CC genotype. The blood pressure and BMI were significantly higher than those of the CC genotype. (3) IAI was correlated negatively with SBP in CT/TT genotype group (r = -0.3519, P = 0.0001), whereas this correlation was not significant in the CC genotype group (r = -0.0055, P = 0.931). The patients were divided into 2 groups according to the median of IAI. In the group with the IAL higher than the median (LnIAI = -5.0016 +/- 0.1830) the SBP of the CT/TT genotype carriers was significantly higher than that of the CC genotype carriers (146 +/- 1.84 mm Hg vs 132 +/- 5.19 mm Hg, P < 0.05). In the group with the IAI lower than the median [IAI(2) = -4.1625 +/- 0.3716] the SBP of the CT/TT genotype carriers was not significantly different from that of the CC genotype carriers (136 +/- 2.4 mm Hg vs 133 +/- 2.0 mm Hg, P > 0.05). The comparison of diastolic pressure showed the similar result. (4) IAI had negatively correlation with SBP in CT/TT genotype carriers without hypertensive family history after controlling age and sex (r = -0.4864 P = 0.001), however, such correlation was not found in CC genotype carriers. CONCLUSION: CT and TT genotype of GNB(3) C825T was correlated with insulin sensitivity, blood pressure, and BMI. GNB(3) C825T gene enhances the hypertensive effect of insulin resistance.