Synthesis and Evaluation of In-Vitro Hepatoprotective Activity of Novel 1,2,3,4- Tetrahydro Quinazoline Derivatives.

Nirmala, R (2014) Synthesis and Evaluation of In-Vitro Hepatoprotective Activity of Novel 1,2,3,4- Tetrahydro Quinazoline Derivatives. Masters thesis, J K K Nataraja College of Pharmacy, Komarapalayam.

Nirmala R.pdf

Download (3MB) | Preview


Medicinal chemistry explains the design and production of compounds that can be used for the prevention, treatment or cure of human and animal diseases. Medicinal chemistry includes the study of already existing drugs, of their biological properties and their structure-activity relationships [1]. Medicinal chemistry was defined by IUPAC specified commission as it concerns the discovery, the development, the identification and the interpretation of the mode of action of biologically active compounds at the molecular level. The resulting liver dysfunction as marked by the increase of SGPT, SGOT and ALP activities. 4a1 and 4a4 decreased the alcohol-induced increase of SGPT, SGOT and ALP activities dose dependently. However, 50 mg/kg bodyweight dose of 4a4 was found to be most effective. This dose was therefore selected for next experiment on time-dependent effect of alcohol. Treatment of alcohol for different time periods (0-35 days) showed a linear increase in the activities of the liver marker enzymes, SGPT, SGOT and ALP till 12 days and at 15th day there was no significant additional effect over day 15.4a1 significantly decreased alcohol-induced increase of enzyme activities, suggesting its hepatoprotective effect. UDP-glucuronosyl transferase (UGT) activity is known to prevent the generation of cellular oxidative stress by glucuronidation and subsequent exclusion of harmful metabolites. UGT therefore plays an important role in the rescue of cellular damage due to stress. This prompted us to investigate UGT in some detail in the liver. Since 50 mg/kg body weight dose of 4a1 was found to be most effective in protecting liver damage, this dose was selected for UGT-related studies. Alcohol treatment affected microsomal UGT activity that was evident from the reduction of PNP-glucuronidation and 4a1 prevented the deterioration of glucuronidation activity effectively. It could be seen from that alcohol treatment caused a significant decrease (p < 0.001) in UGT gene expression while co-treatment with 4a1 protected the down regulation of this gene expression.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Synthesis; Evaluation; In Vitro Hepatoprotective Activity; Tetrahydro Quinazoline Derivatives
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Ravindran C
Date Deposited: 12 Jul 2017 06:08
Last Modified: 12 Oct 2017 03:09

Actions (login required)

View Item View Item