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  • Author: Mohammad A. Hassan x
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Abstract

The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an IC 50 of 0.71 mmol L−1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction via its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors via computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization.

Abstract

Cathinone, the active principle of khat (Catha edulis), stimulates, excites and produces euphoric feelings in khat users. Locomotor and rearing activities, either individual or in groups, of male Swiss albino mice were decreased significantly compared to the control. Motor coordination tests (rotarod, rope climb and grip tests) have shown decreased motor performance in the mice treated with cathinone compared to the control. The elevated plus maze test has shown significant anxiety in the mice compared to the control. Contents of dopamine and its metabolite, homovanillic acid, were increased in the limbic areas compared to the control group. In contrast, contents of 3,4-dihydroxyphenyl acetic acid were depleted significantly and dose dependently compared to the control group in the limbic areas of mice. In conclusion, natural cathinone has depleted motor coordination, accelerated anxiety in mice and altered the contents of dopamine and its metabolites.