NOVEL PYRAZOLINES: SYNTHESIS AND EVALUATION OF THEIR DERIVATIVES WITH ANTICANCER AND ANTI-INFLAMMATORY ACTIVITIES
Objective: Synthesis of novel pyrazolines (P2-P4 & P7-P9) from the chalcones (C2-C10) obtained by condensing different aldehydes with 2-acetyl- 5-bromothiophene and evaluates them for in vitro anticancer and anti-inflammatory activities.
Methods: The synthesized pyrazolines and chalcones were screened for anticancer activity against human breast cancer cell lines-MCF-7 and MDA-MB-468 in the range of 100 nm to 100 Âµm. Inhibition of bovine albumin denaturation and heat-induced hemolysis in vitro methods were followed to screen for anti-inflammatory activity. The structures of synthesized compounds were confirmed based on the IR, 1H NMR and mass spectral data.
Results: Among the synthesized compounds, methoxy trisubstituted pyrazoline derivative (P6) exhibited an interesting profile of anticancer activity against MCF-7 cell line with GI50<0.1 Î¼ M. similar to that of the standard drug doxorubicin. Compounds C8, P8, P3 have moderate anti-inflammatory activity in bovine denaturation and heat induced hemolytic method.
Conclusion: Novel pyrazolines and chalcones were synthesized and evaluated for anticancer and anti-inflammatory activity. The methoxy containing compounds one of which P6 found to be active against MCF-7 breast cancer cell line. The chloro-substituted compounds found to show anti-inflammatory activity.
2. Kristina S, Marijeta K, Ivo P, Lidija S, KreÅ¡imir P, Grace KZ. Synthesis, photochemical synthesis, DNA binding and antitumor evaluation of novel cyano-and amidino-substituted derivatives of naphtho-furans, naphtho-thiophenes, thieno-benzofurans, benzo-dithiophenes and their acyclic precursors. Eur J Med Chem 2006:41;925-39.
3. Sayed MR, Thoraya AF, Magda AA, Mohamed MA, Mohamed RA. New pyrazoles incorporating pyrazolyl pyrazole moiety: Synthesis, anti-HCV and antitumor activity. Eur J Med Chem 2010:45;1042-50.
4. Amol VG, Chetan P, Sahebrao SR, Bhausaheb KK. Synthesis and antimicrobial activity of novel fluorine-containing 4-(substituted-2-hydroxybenzoyl)-1H-pyrazoles and pyrazolylbenzo [d]oxazoles. Bioorg Med Chem Lett 2010:20;5572-6.
5. Steve P, Walter B, Richard JB, David EC, Peter HC, Hazel JD, et al. Identification and optimization of a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors. Bioorg Med Chem Lett 2007:17;370-5.
6. John RG, Francesc PB, Brett MF, Pei Yong S, David MF. Identification of compounds with anti-west nile virus activity. J Med Chem 2006:49;2127-37.
7. Mallikarjuna RJ, Sreeramulu LK, Ravindranath G, Nagaraja Reddy K, Hanumanthurayudu G, Nageswara Reddy A, et al. Synthesis and biological screening of some pyridine and pyrrole derivatives of pyrazolo [3, 4-c] pyrazoles. J Chem Pharm Res 2012;4:272-8.
8. Johnson M, Younglove B, Lee L, LeBlanc R, Holt H, Hills P, et al. Design, synthesis, and biological testing of pyrazoline derivatives of combretastatin-A4. Bioorg Med Chem Lett 2007;17:5897-901.
9. Shaharyar M, Ali MA, Siddiqui AA. Synthesis, structural activity relationship and anti-tubercular activity of novel pyrazoline derivatives. Eur J Med Chem 2007;42:268-75.
10. Ozdemir Z, Kandilci HB, GÃ¼mÃ¼ÅŸel B, CaliÅŸ U, Bilgin AA. Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 2007;42:373-9.
11. Joshi RS, Mandhane PG, Diwakar SD, Dabhade SK, Gill CH. Synthesis, analgesic and anti-inflammatory activities of some novel pyrazolines derivatives. Bioorg Med Chem Lett 2010;20:3721-5.
12. Shaharyar M, Abdullah MM, Bakht MA, Majeed J. Pyrazoline bearing benzimidazoles: search for anticancer agents. Eur J Med Chem 2010;45:114-9.
13. Go ML, Wu X, Liu XL. Chalcones: an update on cytotoxic and chemoprotective properties. Curr Med Chem 2005;12:481-99.
14. Shaharyar M, Abdullah MM, Bakht MA, Majeed J. Pyrazoline bearing benzimidazoles: search for anticancer agents. Eur J Med Chem 2010;45:114-9.
15. Anto RJ, Sukumaran K, Kuttan G, Rao MN, Subbaraju V, Kuttan R. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett 1995;97:33-7.
16. Sugiura K. Effect of various compounds on the Ehrlich ascites carcinoma. Cancer Res 1953;13:431-41.
17. Alba M, Jairo Q, Rodrigo A, Manuel N, Justo C, BraulioI. Synthesis and in vitro antitumor activity of a novel series of 2-pyrazoline derivatives bearing the 4-aryloxy-7-chloroquinoline. Fragment Molecular Orbital 2014;19:18656-75.
18. Ngameni B, Kuete V, Ambassa P, Justin K, Marlyse ML. Synthesis and evaluation of anticancer activity of o-allyl chalcone derivatives. Med Chem 2013;3:233-7.
19. Joshi RS, Mandhane PG, Diwakar SD, Dabhade SK, Gill CH. Synthesis, analgesis, and anti-inflammatory of some novel pyrazoline derivatives. Bioorg Med Chem Lett 2010;20:3721-5.
20. Chandra S, Priyanka C, Protapaditya D, Bhattacharya S. Evaluation of in vitro anti-inflammatory activity of coffee against the denaturation of protein. Asian Pac J Trop Biomed 2012;3:178-80.
21. Jainey PJ, Bhat IK. Antitumor, analgesic, and anti-inflammatory activities of synthesized pyrazolines. J Young Pharm 2012;4:82-7.