Synthesis and Preliminary Evaluation of a Series of Difluorinated Chalcones as Potential Antiproliferative Agents in the Treatment of Breast Cancer

Sachin Ingale; Tabreskhan Pathan; Rhea Mohan; C.S Ramaa

Articles

Vol. 1 No. 3 (2010): July–September 2010

Synthesis and Preliminary Evaluation of a Series of Difluorinated Chalcones as Potential Antiproliferative Agents in the Treatment of Breast Cancer

Sachin Ingale^▸^▾
Tabreskhan Pathan^▸^▾
Rhea Mohan^▸^▾
C.S Ramaa^▸^▾

Requires Subscription or Fee pdf (INR 2000)

Submitted: November 24, 2024
Published: 2010-08-15

Abstract

In the present work, twelve difluorinated chalcone derivatives (1a-1l) were synthesized and evaluated for their antiproliferative activity at Tata Memorial’s Advanced Center for Treatment, Research and Education in Cancer (ACTREC), India, in a panel of four cancer cell lines using four concentrations at 10-fold dilutions. Sulforhodamine B (SRB) protein assay was used to estimate cell stability or growth. Though the compounds showed varying degrees of cytotoxicity in the tested cell lines, most marked effect was observed in breast cancer cell line (MCF7), wherein eleven of the twelve synthesized chalcones showed good antiproliferative activity. These chalcones were then subjected to preliminary docking studies on histone methyltransferase enzyme which suggests that inhibition of histone methylation could be a possible mechanism for their cytotoxic effects.

References

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Keywords

Difluorinated chalcones
SRB assay
breast cancer
docking
histone methyltransferase

How to Cite

Ingale, S., Pathan, T., Mohan, R., & Ramaa, C. (2010). Synthesis and Preliminary Evaluation of a Series of Difluorinated Chalcones as Potential Antiproliferative Agents in the Treatment of Breast Cancer . International Journal of Drug Design and Discovery, 1(3), 209–215. Retrieved from https://ijddd.com/index.php/ijddd/article/view/27

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[1] [1] Gacche, R.; Khsirsagar, M.; Kamble, S.; Bandgar, B.; Dhole, N.; Shisode,K; Chaudhari, A. Chem. Pharm. Bull., 2008, 56(7), 897.

[2] [2] Rao, Y.K.; Shih-Hua, F.; Yew-Min T. Bioorg. Med. Chem., 2004, 12, 2679.

[3] [3] Jahng Y., Zhao L.; Moon Y., Basnet A.; Kim E.; Chang H. W.; Ju H. K.; Jeong T. C.; Lee E. S. Bioorg. Med. Chem. Lett., 2004, 14, 2559.

[4] [4] Modzelewska , A.; Pettit, C.; Achanta G.; Davidson,N. E.; Huang P.;Khan S. R. Bioorg. Med. Chem., 2006, 14, 3491.

[5] [5] Suksamrarn, A.; Poomsing P.; Aroonrerk N.; Punjanon T.; Suksamrarn S.; Kongkun S. Arch. Pharm. Res., 2003, 26, 816.

[6] [6] Dominguez, J. N.; Leon C.; Rodrigues J.; Dominguez N. G. D.; Gut J.;Rosenthal P. J. J. Med. Chem., 2005, 48, 3654.

[7] [7] Narender T.; Khaliq T.; Shweta; Nishi; Goyal, N.; Gupta, S. Bioorg. Med. Chem., 2005, 13, 6543.

[8] [8] Opletalova V.; Ceska Slov. Farm., 2000, 49, 278.

[9] [9] Jadhav, D.H.; Ramaa C.S. Indian J. Chem., 2007, 46B, 2064.

[10] [10] More, A.H.; Ramaa C. S. Indian J. Chem., 2010, 49B, 364.

[11] [11] Rayburn, E. R.; Ezell, S. J.; Zhang, R. Mol. Cell. Pharmacol., 2009, 1(1), 29.

[12] [12] Waddell, W.R.; Loughry, R.W. J. Surg. Oncol., 1983, 24, 83.

[13] [13] Wang, D.; Dubois R.N. Gut, 2006, 55, 115.

[14] [14] Zlotnik, A. Contrib. Microbiol., 2006, 13, 191.

[15] [15] Jana, N.R. Cell Mol. Life Sci., 2008, 65, 1295.

[16] [16] de Groot, D.J.; de Vries, E.G; Groen, H.J.; de Jong,S. Crit. Rev. Oncol. Hematol., 2007, 61, 52.

[17] [17] Momose,Y.; Meguro, K.; Ikeda, H.; Hatanaka, C.; Oi S.; Sohda., T. Chem. Pharm. Bull., 1991, 39 (6), 1440.

[18] [18] Monks, A; Scudiero, D.; Skehan, P.; Shoemaker, R.; Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A. J. Natl. Cancer Inst., 1991, 83 (11), 757.

[19] [19] Boyd, M. R.; Paull, K. D. Drug Dev. Res., 1995, 34, 91.

[20] [20] Spannhoff, A., Sippl, K; Jung, M. Int. J. Biochem. Cell Biol., 2009, 41, 4.

[21] [21] Trievel, R.C. Crit. Rev. Eukaryot Gene Expr., 2004, 14, 147.

[22] [22] Morgunkova, A. Barley, N.A. Cell Cycle., 2006, 5, 1308.

[23] [23] Bedford, M.T. Richard, S. Mol. Cell., 2005, 18, 263.

[24] [24] Qian, C. Zhou, M.M. Cell Mol. Life Sci., 2006, 63, 2755.

[25] [25] Krause, C.D. Yang, Z.H.; Kim, Y.S.; Lee, J.H.; Cook, J.R.; Restka, S. Pharmacol. Ther., 2007, 113, 50.

[26] [26] Mai, A. Cheng, D.; Bedford, M.T., Valete, S., Nebbioso, A., Perrone, A., Brosch, G., Sbardella, G., de Bellis, F., Mxceli, M., Altucci, L., J. Med. Chem., 2008, 51, 2279.