SYNTHESIS AND ASSESSMENT OF HEPATOPROTECITVE ACTIVITY OF SOME NEW 2-ARYL TETRAHYDROQUINOLINE AND SPIROOXYINDOLYL TETRAHYDROQUINOLINE DERIVATIVES
Objective: To evaluate the hepatoprotecitve potential of some newly synthesized tetrahydroquinoline derivatives against carbon tetrachloride induced hepatic damage in wister rats.
Methods: A series of 2-aryl, 4-N vinyl pyrrolido/caprolacto and spirooxy indolyl tetrahydroquinolines were synthesized by imino Diels-Alder reaction using Antimony (III) sulfate as catalyst. The titled compounds were characterized by IR, 1HNMR spectroscopy and screened for hepatoprotecitve activity. Hepatopotoxicity was induced in male Wister rats by intrperitoneal injection of CCl4. Wister rats weighing 150-200g were randomly assigned in to various groups of six animals each. Group I â€“ Normal control received only 1% Tween in distilled water, Group II â€“ Served as negative control received CCl4 in liquid paraffin 1 ml/kg p. o. at every 72 h for 10 days. Group III â€“ X were intoxicated with CCl4 1 ml/kg p. o. before the administration of Silymarin 100 mg/kg p. o. and suspension of synthetic derivatives in polyethylene glycol-400 at the dose of 25 mg/kg p. o. for 10 days. Different hepatic biochemical parameters viz. SGOT, SGPT, SALP, Total and direct bilirubin were evaluated before and after treatment to investigate the hepatoprotecitve activity.
Results: It was observed that in CCl4 intoxicated group; total and direct bilirubin, SGOT, SGPT, SALP levels were significantly increased as compared to control group. Administration of synthesized tetrahydroquinoline derivatives at the dose of 25 mg/kg p. o. reduced these pathological damages caused by CCl4 intoxication compared to normal and Silymarin treated groups.
Conclusion: The present study revealed that synthesized tetrahydroquinoline derivatives, showed hepatoprotecitve potential against CCl4 induced hepatotoxicity in wister rats, thus offering a novel synthetic formulation as a hepatoprotecitve drug.
2. Lee KJ, Woo ER, Choi CY, Shin DW, Lee DG, Youth HG. Protective effect of acetoside on carbon tetrachloride induced hepatotoxicity. J Life Sci 2004;74:1015-64.
3. Pradhan SC, Girish C. Hepatoprotecitve herbal drugs silymarin from experimental pharmacology to clinical medicine. Indian J Med Res 2006;124:491-504.
4. Dorey G, Lokkhart B, Lastage P, Casara P. In vitro antiamoebic activities. Biorg Med Chem Lett 2000;10(9):935-42.
5. Roach SL, Hignchi RI, Adams ME, Lice Y, Karanewsky DS, Marchke KB, et al. Non steroidal glucortic acid receptor legends bond on 6-indole. Biorg Med Chem Lett 2008;18(12):3504-8.
6. Hartmann RW, Erotschar M, Arch P. Treatment of 99 with 10% NaOH leads to the formation of intermediate. Arch Pharm 1999;322(10):358.
7. Uchida M, Chihiro M, Morita S, Kanbe T, Yamashita H, Yamasaki K, et al. Inhibitors 8 (5 fluoro 2 benzimidazolyl-5,6,7,8 tetrahydroquinolines showed-). Chem Pharm Bull 1989;37(8):2109.
8. Caroll FI, Blackwell JJ, Philip A, Twine CE. Reduced 8-aminoquinoline analogue as a potential antimalarial agent. J Med chem 1976;10(9):1111-9.
9. Pradhan R. Synthesis and crystal structure of two novel drugs. Tetrahedron 2006;62:779.
10. Reed IJ, Munch H. Toxicity studies on experimental animals. Am J Hygne 1938;27:493-8.
11. Shukla DS, Ravishankar VJ, Bhavsar GC. Preliminary study on hepatoprotecitve activity. Fitoterapia 1996;67:106.
12. Rietman. A coloric method for the determination of SGOT, SGPT. Am J Clin Path 1957;28:56.
13. King EJ. A method for the determination of tartarate-labile prostatic acid in serum. Am J Clin Path 1959;12:85-7.
14. Jendrassik FL, Grof P. Manual of medical lab techniques. Biochem 1938;81:297-301.
15. Dunnet CW. A new table for multiple comparisons with a control. Biometrics 1964;20:482.
16. Brattin WJ, Glende EA, Recknagel RO. An approach to free radicals in medicine and biology. Bio Med 1985;1:27.
17. Ahmad S, Raharah A, Alam A, Saleem M, Sultan S. Activity of bark. J Ethano Pharmacol 2000;69:157-61.
18. Kyung Jin Le, Eun-Rhan Woo, Chul Yung Choi, Ho Jinyou. Threat to public health owing to its life threating complications-on CCl4 induced hepatotoxicity. Life Sci 2004;74:105-64.
19. Be-Jen Wang, Chu-ting Liu, Chin Yia tsung, Chein Ping Wu. Trace metal concentration-food sources for fish and birds in-absorbed and adsorbed metals. Food Chem Toxicol 2004;42:609-13.
20. Recknagel RO, Glende EA, Dolak JA, Aller RL. Mechanism of CCl4 toxicity. Pharmacol Ther 1989;43:139-43.
21. Achliya GS, Kotgale SG, Wadodkar AK, Dorie AK. Hepatoprotecitve activity of Panchgavya ghrita against CCL4 induced hepatotoxicity in rats. Indian J Pharmacol 2003;35:311-4.
22. Moss DW, Butterworth PS. Protection of rats by extract of some common Nigerian trees against-In: â€™Ethanol and Med. Pitman Medicaâ€™, London; 1974;2:139-43.
23. Mukerjee PK. Quality control and herbal drugs, Ist edn. Business horizons pharmaceutical publications, New Delhi; 2001. p. 531-5.