SYNTHESIS AND CHARACTERIZATION OF NEW IMINE AND PTHALIC ACID DERIVATIVES OF URSOLIC ACID
Objective: The current work envisages synthesis of novel ursolic acid derivatives and characterization by spectral methods that can be possible candidates for anti-inflammatory and anticancer activity.
Methods: A series of imine and phthalic acid derivatives of ursolic acid (3Î²-hydroxyurs-12-en-28-oic acid), have been synthesized. 3-hydroxyimino-urs-12-en-28-olic acid was treated with alkyl halide in the presence of sodium hydride in ethanol to yield 3-alkyloxyimino-urs-12-en-28-oic acid and further converted to its ester derivatives. Ursolic acid was reacted with phthalic anhydride in pyridine to get mono and di-substituted ester derivatives.
Results: Novel substituted imino and pthalic derivatives were synthesized. The compounds synthesized were characterized by MS, IR, 1H and C-NMR spectroscopy.
Conclusion: The derivatives prepared may facilitate designing of similar newer analogues which may be useful for generating possible candidates from ursolic acid for anti-imflammatory and anti-cancer potential. Ursolic acid oximes and its anhydrides exhibit valuable biological properties and are important starting materials for further transformations.
2. Babar SB, Laddha KS. Extraction, isolation and synthesis of derivatives of ursolic acid. Indian Drugs 2012;49:33-7.
3. Jie L. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 1995;49(2): 57-68.
4. Chun J, Lee C, Hwang SW, Im JP, Kim JS. Ursolic acid inhibits nuclear factor-ÎºB signaling in intestinal epithelial cells and macrophages, and attenuates experimental colitis in mice. Life Sci 2014;110(1):23-34.
5. XuemeiW, Fan Z, Ling Y, Ying M, Hai L, Xiaowen Z, et al. Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo. J Biomed Biotechnol 2011;2011:419343.
6. Deng L, Zhang R, Tang F, Li C, Xing YY, Xi T. Ursolic acid induces U937 cells differentiation by PI3K/Akt pathway activation. Chin J Nat Med 2014;12(1):15-19.
7. Rashid S, Dar BA, Majeed R, Hamid A, Bhat BA. Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents. Eur J Med Chem 2013;66:238-45.
8. Tu HY, Huang AM, Wei BL, Gan KH, Hour TC, Yang SC, et al. Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species. Bioorg Med Chem 2009;17(20):7265-74.
9. Leal AS, Wang R, Salvador JA, Jing Y. Synthesis of novel ursolic acid heterocyclic derivatives with improved abilities of antiproliferation and induction of p53, p21waf1 and NOXA in pancreatic cancer cells. Bioorg Med Chem 2012;20(19):5774-86.
10. Ma CM, Cai SQ, Cui JR, Wang RQ, Tu PF, Hattori M, et al. The cytotoxic activity of ursolic acid derivatives. Eur J Med Chem 2005;40(6):582-9.
11. Liu D, Meng Y, Zhao J, Chen L. Synthesis and anti-tumor activity of novel amide derivatives of ursolic acid. Chem Res Chin Univ 2008;24(1):42â€“6.
12. Chen J, Liu J, Zhang L, Wu G, Hua W, Wu X, et al. Pentacyclic triterpenes. Part 3: Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of glycogen phosphorylase. Bioorg Med Chem Lett 2006;16(11):2915-9.
13. E Silva Mde L, David JP, S lva LC, Santos RA, David JM, Lima LS, et al. Bioactive oleanane, lupane and ursane triterpene acid derivatives. Molecules 2012;17(10):12197-205.