The effects of various doses of lycopene were studied in streptozotocin (STZ)-induced hyperglycaemic rats to evaluate its possible hypoglycaemic, hypolipidaemic and antioxidant activity in diabetes. Compared to the normoglycaemic group, the treatment of rats with a single dose of STZ (65 mg/kg body weight) revealed a significant increase (p<0.05) only in plasma hydrogen peroxide (H(2)O(2)), i.e. by 230%; it increased the thiobarbituric acid reactive substances (TBARS) as index of the lipid peroxidation level by 69%, while total antioxidant activity was decreased by 36%, with a consistently significant decrease (p<0.05) in the activity of erythrocytes antioxidative enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). The levels of total lipid, triglycerides and total cholesterol in serum of hyperglycaemic rats were increased by 14%, 65% and 36%, respectively, while HDL-C decreased by 22% compared to the normoglycaemic group. Exogenous administration of individual gradual doses of lycopene to hyperglycaemic rats causes a dose-dependent decrease in glucose level, an increase of insulin concentration, a decrease of H(2)O(2) and TBARS levels, as well as increased total antioxidant status with increased antioxidant enzyme activities (CAT, SOD and GPx) with improvement in serum lipid profile. It is obvious from this study that lycopene acts as an antidiabetic agent through lowering the free radical and has an improving effect on serum that reaches the normal level; the greatest effect of lycopene was observed at 90 mg/kg body weight.

In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as VEGFR-2 inhibitors targeting hepatocellular carcinoma. Our design strategy is two-fold; it aimed first at studying the effect of replacing the 5-methylfuryl moiety of the well-known antiangiogenic 2-furylbenzimidazoles with an isopropyl moiety on the VEGFR-2 inhibitory activity and the cytotoxic activity. Our second objective was to further optimize the structures of the benzimidazole derivatives through elongation of the side chains at their one-position for the design of more potent type II-like VEGFR-2 inhibitors. The designed 1,2-disubstituted benzimidazoles demonstrated potent cytotoxic activity against the HepG2 cell line, reaching IC₅₀ = 1.98 μM in comparison to sorafenib (IC₅₀ = 10.99 μM). In addition, the synthesized compounds revealed promising VEGFR-2 inhibitory activity in the HepG2 cell line, e.g., compounds 17a and 6 showed 82% and 80% inhibition, respectively, in comparison to sorafenib (% inhibition = 92%). Studying the effect of 17a on the HepG2 cell cycle demonstrated that 17a arrested the cell cycle at the G2/M phase and induced a dose-dependent apoptotic effect. Molecular docking studies of the synthesized 1,2-disubstituted benzimidazoles in the VEGFR-2 active site displayed their ability to accomplish the essential hydrogen bonding and hydrophobic interactions for optimum inhibitory activity.