Serdar BURMAOĞLU

Fluoro-Substituted Chalcones as the Compounds Having Anticancer Activity

Chalcones consist of open chain flavonoids in which the two aromatic rings are linked by three carbons and have and/or α, β-unsaturated, saturated carbonyl systems in their open chains. Chalcones are important compounds with simple chemistry that have easy synthetic access to yield various substituted derivatives. In recent years the number chalcones as potential lead drugs containing fluorine in their structures have become quite common. It has been reported that insertion of a fluorine atom into a biologically active compound results in minimum steric changes and eases the interactions between the enzymes active sites and other biological systems. This mini review intends the most recent updates on anticancer potential of fluoro-substituted chalcones.

Anti-Kanser Aktiviteye Sahip Bileşikler Olarak Flor-Sübstitüe Kalkonlar

Kalkonlar iki aromatik halkanın üç karbonla birbirine bağlandığı ve düz zincirinde α, β-doymamış bir karbonil veya doymuş bir karbonilgrubu olan açık zincirli flavonoidlerdir. Kalkonlar basit kimyaya sahip ve kolaylıkla türevlendirilebilen önemli bileşiklerdir. Son yıllardayapılarında flor atomu ihtiva eden potansiyel ilaç adayı olabilecek kalkonlar oldukça yaygın hale gelmiştir. Flor atomunun biyolojikolarak aktif bir molekülün yapısında yer alması minimum sterik etki göstermesine sebep olduğu ve enzimlerin aktif bölgeleri ve diğerbiyolojik sistemlerle etkileşimi kolaylaştırdığı bildirilmektedir. Bu mini derleme, flor-sübstitüe kalkonların potansiyel antikanser etkiliilaç geliştirme çalışmalarındaki son gelişmelerin derlenmesini amaçlamaktadır.

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Abdel-Aziz, M., Park, S., El-Din, G., Abuo-Rahma, AA., Sayed, MA., Kwon, Y. 2013. Novel N-4-piperazinylciprofloxacin-chalcone hybrids: synthesis, physicochemical properties, anticancer and topoisomerase I and II inhibitory activity. Eur. J. Med. Chem., 69: 427-438.
Al-Masum, M., Ng, E., Wai, M. C., 2011. Palladium-catalyzed direct cross-coupling of potassium styryltrifluoroborates and benzoyl chlorides—a one step method for chalcone synthesis. Tetrahedron Lett., 52: 1008–1010.
Biswas, BB., Sen, K., Ghosh Choudhury, G., Bhattacharyya, B. 1984. Molecular biology of tubulin: Its interaction with drugs and genomic organization. J. Biosci., 6 (4): 431-457.
Bohm, A. 1998. Introduction to flavonoids, Harwood Academic Pub; London.
Burmaoglu, S., Algul, O.,. Anıl, DA., Gobek, A., Duran, GG., Ersan, RH., Duran, N. 2016. Synthesis and anti-proliferative activity of fluoro-substituted chalcones, Bioorg. Med. Chem. Lett., 26: 3172–3176.
Ducki, S., Mackenzie, G., Greedy, B., Armitage, S., Chabert, JFD., Bennett, E., Nettles, J., Snyder, JP., Lawrence, NJ. 2009. Combretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: structure-based discovery of alpha-aryl chalcones, Bioorg. Med. Chem., 17: 7711-7722.
Eddarir, S., Cotelle, N., Bakkour, Y., Rolando, C. 2003. An efficient synthesis of chalcones based on the Suzuki reaction, Tetrahedron Lett., 44: 5359–5363.
Hagmann, WK., 2008. The Many Roles for Fluorine in Medicinal Chemistry, J. Med. Chem., 51(15): 4359-4369.
Jain, UK., Bhatia, RK., Rao, AR., Singh, R.,. Saxena, AK, Sehar, I. 2014. Design and development of halogenated chalcone derivatives as potential anticancer agents, Trop. J. Pharm. Res., 13(1): 73-80.
Karthikeyan, C., Moorthy, N. S. H. N., Ramasamy, S., Vanam, U., Manivannan, E., Karunagaran, D., Trivedi, P. 2015. Advances in chalcones with anticancer activities. Recent Patents on Anti-Cancer Drug Discovery, 10: 97-115.
Kumar, A., Sharma, S., Tripathi, V. D., Srivastava S., 2010. Synthesis of chalcones and flavanones using JuliaeKocienski olefination, Tetrahedron, 66: 9445-9449.
Larsen, AK., Escargueil, AE., Skladanowski, A., 2003. Catalytic topoisomerase II inhibitors in cancer therapy, Pharmacol. Ther., 99(2): 167-181.
Lawrence, NJ., Patterson, RP., Ooi, L., Cook, D., Ducki, S., 2006. Effects of a-substitutions on structure and biological activity of anticancer chalcones, Bioorg. Med. Chem. Lett., 16: 5844-5848.
Le Gall, C., Bellahcene, A., Bonnelye, E., Gasser, JA., Castronovo, V., Green, J., Zimmermann, J., Clezardin, P., 2007. A cathepsin K inhibitor reduces breast cancer induced osteolysis and skeletal tumor burden. Cancer Res., 67 (20): 9894-9902.
Lodish, H., Berk, A., Zipursky, SL., Matsudaira, P., Baltimore, D., Darnwell, J., 2000. Molecular Cell Biology, fourth ed., W. H. Freeman, New York, The Role of Topoisomerases in DNA Replication.
Mahapatra, DK., Bharti, SK., Asati, V. 2015. Anti-cancer chalcones: Structural and molecular target perspectives. Eur. J. Med. Chem., 98: 69-114.
Mandelkow, E., Mandelkow, EM. 1989. Microtubular structure and tubulin polymerization. Curr. Opin. Cell. Biol., 1: 5-9.
Matos, MJ., Vazquez-Rodriguez, S., Uriarte, E., Santana, L. 2015. Potential pharmacological uses of chalcones: a patent review (from June 2011 – 2014), Expert Opin. Ther. Patents, 25(3): 351-366.
Nakhjavania, M., Zarghib, A., Shirazi, FH. 2014. Cytotoxicity of selected novel chalcone derivatives on human breast, lung and hepatic carcinoma cell lines, Iran. J. Pharm. Res., 13(3): 953-958.
Ojima, I. 2009. Fluorine in Medicinal Chemistry and Chemical Biology; Blackwell Publishing, Ltd., p 3, Part I.
Padhye, S., Ahmad, A., Oswal, N., Dandawate, P., Rub, R. A., Deshpande, J., Swamy, K. V., Sarkar, FH. 2010. Fluorinated 2’-hydroxychalcones as garcinol analogs with enhanced antioxidantand anticancer activities, Bioorg. Med. Chem. Lett., 20: 5818-5821.
Ramalho, SD., Bernades, A., Demetrius, G., Noda-Perez, C., Vieira, PC., Dos Santos, CY., Da Silva, J.A., De Moraes, MO., Mousinho, KC. 2013. Synthetic chalcone derivatives as inhibitors of cathepsins K and B, and their cytotoxic evaluation, Chem. Biodivers., 10: 1999-2006.
Shi, HB., Zhang, SJ., Ge, QF., Guo, DW., Cai, CM., Hu, WX. 2010. Synthesis and anticancer evaluation of thiazolylchalcones. Bioorg. Med. Chem. Lett., 20(22): 6555-6559.
Sun, L. P., Gao, L. X., Ma, W. P., Nan, F. J., Li, J., Piao, HR. 2012. Synthesis and Biological Evaluation of 2,4,6-Trihydroxychalcone Derivatives as Novel Protein Tyrosine Phosphatase 1B Inhibitors. Chem. Biol. Drug. Des., 80: 584-590.
Vitorovic-Todorovica, MD., Eric-Nikolic, A., Kolundzija, B., Hamel, E., Ristic, S., Juranic, IO., Drakulic, BJ., 2013. (E)- 4-aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: design, antiproliferative activity and inhibition of tubulin polymerization. Eur. J. Med. Chem., 62., 40-50.
WHO, 2015. http://www.who.int/mediacentre/factsheets/fs297/ en/Accessed Jan 5, 2015.
Zhang, H., Liu, JJ., Sun, J., Yang, XH., Zhao, TT., Lu, X. 2012. Design, synthesis and biological evaluation of novel chalcone derivatives as antitubulin agents. Bioorg Med Chem., 20(10): 3212-8.
Zhao, S. L., Peng, Z., Zhen, XH., Jin, HG., Han, Y., Qu, YL.,. Guan, LP. 2015. Potent CDC25B and PTP1B phosphatase inhibitors: 2’,4’,6’-trihydroxylchalcone derivatives. Med Chem Res., 24: 2573–2579.
Zou, G., Guo, J., Wang, Z., Huang, W., Tang, J. 2007. Hecktype coupling vs. conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,betaunsaturated carbonyl compounds: a systematic investigation, Dalton Trans., 28: 3055-3064.