Potential acetylcholinesterase inhibitors to treat Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is identified by neuropathological symptoms, and there is now no effective treatment for the condition. A lack of the brain neurotransmitter acetylcholine has been related to the etiology of Alzheimer's disease. Acetylcholinesterase is an enzyme that breaks down acetylcholine to an inactive form and causes the death of cholinergic neurons. Conventional treatments were used but had less effectiveness. Therefore, there is a crucial need to identify alternative compounds with potential anti-cholinesterase agents and minimal undesirable effects. MATERIALS AND METHODS: Fluoroquinolones and benzimidazole-benzothiazole derivatives offer antimicrobial, anti-inflammatory, anti-oxidant, anti-diabetic, and anti-Alzheimer activities. To enhance the chemical portfolio of cholinesterase inhibitors, a variety of fluoroquinolones and benzimidazole-benzothiazole compounds were evaluated against acetylcholinesterase (AChE) butyrylcholinesterase (BChE) enzymes. For this purpose, molecular docking and adsorption, distribution, metabolism, excretion, and toxicology ADMET models were used for in-silico studies for both AChE and BChE enzymes to investigate possible binding mechanisms and drug-likeness of the compounds. The inhibitory effect of docked heterocyclic compounds was also verified in vitro against AChE and BChE enzymes. Fluoroquinolones (Z, Z3, Z4, Z6, Z8, Z12, Z15, and Z9) and benzimidazole-benzothiazole compounds (TBIS-16, TBAF-1 to 9) passed through the AChE inhibition assay and their IC50 values were calculated. RESULTS: The compound 1-ethyl-6-fluoro-7-(4-(2-(4-nitrophenylamino)-2-oxoethyl)piperazin-1-yl) -4-oxo-1,4 di-hydroquinoline-3-carboxylic acid and 2-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(3-bromobenzyl)-4-hydroxy-2H-thiochromene-3-carbohydrazide 1,1-dioxide (Z-9 and TBAF-6) showed the lowest IC50 values against AChE/BChE (0.37±0.02/2.93±0.03 µM and 0.638±0.001/1.31±0.01 µM, respectively) than the standard drug, donepezil (3.9±0.01/4.9±0.05 µM). During the in-vivo investigation, behavioral trials were performed to analyze the neuroprotective impact of Z-9 and TBAF-6 compounds on AD mouse models. The groups treated with Z-9 and TBAF-6 compounds had better cognitive behavior than the standard drug. CONCLUSIONS: This study found that Z-9 (Fluoroquinolones) and TBAF-6 (benzimidazole-benzothiazole) compounds improve behavioral and biochemical parameters, thus treating neurodegenerative disorders effectively.

Beneficial effects of Naringin against lopinavir/ ritonavir-induced hyperlipidemia and reproductive toxicity in male albino rats.

OBJECTIVE: This research work was planned to determine whether Naringin (NG) had any protective effects against lopinavir/ritonavir (LR)-induced alterations in blood lipid levels, hepatotoxicity, and testicular toxicity. MATERIALS AND METHODS: Four groups of six rats each were used for the study: Control (1% ethanol), naringin (80 mg/kg), lopinavir (80 mg/kg)/ritonavir (20 mg/kg), and lopinavir (80 mg/kg)/ritonavir (20 mg/kg) + naringin (80 mg/kg). The drug treatment was continued for 30 days. On the last day, the serum lipid fractions, liver biochemical parameters, testicular antioxidants (enzymatic and non-enzymatic), and the histopathology of the liver and testis tissue were assessed for all rats. RESULTS: Treatment with NG decreased significantly (p<0.05), the baseline serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C). But these parameters were significantly (p<0.05) increased in LR-treated animals. Naringin, co-administered with LR, restored the liver and testicular biochemical, morphological, and histological balance. CONCLUSIONS: This study shows that NG can be used as a treatment for LR-induced biochemical and histological changes in the liver and testes and changes in serum lipid levels.