Síntese e avaliação biológica de chalconas e derivados in vitro contra célula AGP01

Maricelia Lopes dos  Anjos; Herald Souza dos  Reis; Heriberto Rodrigues  Bitencourt; Natasha Costa da Rocha  Galucio; André Salim  Khayat; Antônio Pedro da Silva  Souza Filho; Marta Chagas  Monteiro

doi:10.33448/rsd-v10i16.23600

Autores/as

Maricelia Lopes dos Anjos Universidade Federal do Pará https://orcid.org/0000-0001-6837-0276
Herald Souza dos Reis Universidade Federal do Pará https://orcid.org/0000-0001-6513-3937
Heriberto Rodrigues Bitencourt Universidade Federal do Pará https://orcid.org/0000-0002-0003-2876
Natasha Costa da Rocha Galucio Universidade Federal do Pará https://orcid.org/0000-0003-4923-1478
André Salim Khayat Universidade Federal do Pará https://orcid.org/0000-0002-3451-6369
Antônio Pedro da Silva Souza Filho Embrapa Amazônia Oriental https://orcid.org/0000-0001-9213-2139
Marta Chagas Monteiro Universidade Federal do Pará https://orcid.org/0000-0002-3328-5650

DOI:

https://doi.org/10.33448/rsd-v10i16.23600

Palabras clave:

Chalcona; Flavanonas; Antiproliferativo.

Resumen

El interés en la obtención de calconas se debe a las numerosas actividades farmacológicas descritas en la literatura para estos compuestos que son intermediarios en la biosíntesis de flavonoides. De esta forma, la síntesis y caracterización de varias calconas y derivados adquiere importancia para el desarrollo de compuestos con actividad antiproliferativa. En este trabajo se sintetizaron diez sustancias, siete chalconas y tres naftoflavanonas, obtenidas mediante la reacción de condensación aldólica de Claisen Schmidt entre acetofenonas y aldehídos, a temperatura ambiente en un medio básico. Los rendimientos oscilaron entre el 65,35% y el 97,45%. Estar caracterizado y confirmado mediante técnicas espectroscópicas de RMN ¹H y ¹³C en comparación con los datos de la literatura. Todos los productos sintetizados se sometieron al ensayo de citotoxicidad de bromuro de 3- (4,5-dimetiltiazol-2-il) -2,5-difeniltetrazolio (MTT), para evaluar la actividad antiproliferativa in vitro, en linaje tumoral gástrico (AGP01), en comparación con la línea de células pulmonares normales (MRC-5). Las sustancias más activas fueron las chalconas 2, 6, 3, 4 y 1 que mostraron la mayor reducción en la viabilidad celular de AGP01, siendo superior al 90%.

Citas

Ahmad, M. R., Sastry, V. G., Bano, N. & Anwar, S. (2016). Synthesis of novel chalcone derivatives by conventional and microwave irradiation methods and their pharmacological activities. Arab J Chem, 9, 931–935. http://dx.doi.org/10.1016/j.arabjc.2011.09.002

Alard, E., Butnariu, A-B., Grillo, M., Kirkham, C., Zinovkin, D. A., Newnham, L., Macciochi, J. & Pranjol, M. Z. I. (2020). Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets. Cancers, 12, 1826. DOI:10.3390/cancers12071826

Anwar, C., Prasetyo, Y. D., Matsjeh, S., Haryadi, W., Sholikhah, E. N., Nendrowati. (2018). Synthesis of Chalcone Derivatives and Their in vitro Anticancer Test against Breast (T47D) and Colon (WiDr) Cancer Cell Line. Indones. J. Chem., 18 (1), 102 - 107. DOI: 10.22146/ijc.26864

Attar, S., O’brien, Z., Alhaddad, H., Golden, M. L. & Calderón-Urrea, A. (2011). Ferrocenyl chalcones versus organic chalcones: A comparative study of their nematocidal activity. Bioorg Med Chem, 19, 2055–2073. DOI: 10.1016/j.bmc.2011.01.048.

Bitencourt, H. R.; de Albuquerque, C. A. B.; Souza Filho, A. P. S.; dos Anjos, M. L.; Maciel, C. J. A.; Pina, J. R. S.; Pinheiro, J. C.; de Carvalho, L. L. P. P.; Marinho, A. M. R.; de Almeida, O. (2020a). Análise dos Produtos de Reação da Condensação entre 2-Hidróxiacetofenona e p-Anisaldeído em Meio Básico. In: A química nas áreas natural, tecnológica e sustentável. Vol. 3. p. 26-34. Organizadora Érica de Melo Azevedo. – Ponta Grossa, PR: Atena Editora. DOI 10.22533/at.ed.8422017093.

Bitencourt, H. R.; Marinho, A. M. R.; Souza Filho, A. P. S.; Pinheiro, J. C.; Tavares, M. G. C.; de Almeida, O; Farias, R. A. F. (2020b). Síntese de chalconas. In: Processos Químicos e Biotecnológicos. Vol. 6. p. 57-66. Organizador Darly Fernando Andrade. Belo Horizonte-MG. Editora Poisson. DOI 10.36229/978-65-5866-009-5.

Bézivin, C.; Tomasi, S.; Lohézic-Le, D.; Boustie, F. J. (2003). Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine, 10, 499‐503. Doi:10.1078/094471103322331458.

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A. & Jemal, A. (2018). Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA CANCER J CLIN, 68, 394–424. DOI: 10.3322/caac.21492. Available online at cacancerjournal.com.

Das, M. & Manna K. (2016). Chalcone Scaffold in anticancer armamentarium: a molecular insight. J. Toxicol, 2016, 1–4. http://dx.doi.org/10.1155/2016/7651047

De Mello, T. F. P.; Bitencourt, H. R.; Pedroso, R. B.; Aristides, S. M. A.; Lonardoni, M. V. C.; Silveira, T. G. V. (2014). Leishmanicidal activity of synthetic chalcones in Leishmania (Viannia) braziliensis. Exp Parasitol. 136, 27-34. Doi: 10.1016/j.exppara.2013.11.003.

Devi, L. D., Aswini, R., Kothai, S. Synthesis And Characterisation Of Chalcone Based Copolyesters And Their Anticancer Activity. (2018). IJPSR, 9(4), 1589-1593. DOI: 10.13040/IJPSR.0975-8232.9(4).1589-93

Echeverria, C., Santibañez, J. F., Donoso-Tauda, O., Escobar, C. A., Ramirez-Tagle, R. (2009). Structural Antitumoral Activity Relationships of Synthetic Chalcones. Int. J. Mol. Sci., 10, 221-231. DOI:10.3390/ijms10010221

Ferlay, J., Colombet, M., Soerjomataram, I., Mathers, C., Parkin, D.M., Piñeros, M., Znaor, A. & Bray, F. (2019). Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer, 144, 1941–1953. DOI: 10.1002/ijc.31937

Fiorica, F., Trovò, M., Ottaiano, A., Nasti, G., Carandina, I., Marzola, M., Paoli, P. & Berretta, M. (2018). Can the addition of radiotherapy postoperatively increase clinical outcome of patients with gastric cancer? A systematic review of the literature and meta-analysis. Oncotarget, 9 (12), 10734-10744. DOI: 10.18632/oncotarget.23754

Fu, Y., Liu, D., Zeng, H., Ren, X., Song, B., Hu, B. (2020). New chalcone derivatives: synthesis, antiviral activity and mechanism of action. RSC Adv. 10, 24483–24490. DOI: 10.1039/d0ra03684f

Ismail, N. L., Ming-Tatt L, Lajis, N. L., Akhtar, M. N., Akira, A., Perimal, E. K., Israf, D. A. & Sulaiman, M. R. (2016). Antinociceptive Effect of 3-(2,3-Dimethoxyphenyl)-1- (5-methylfuran-2-yl) prop-2-en-1-one in Mice Models of Induced Nociception. Molecules, 21, 1077. DOI:10.3390/molecules21081077

Isoda, H., Motojima, H., Onaga, S., Samet, I., Villareal, M. O & Han, J. (2014). Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells. Chem Biol Interact, 220, 269–277. http://dx.doi.org/10.1016/j.cbi.2014.07.006

Kotha, R. R., Kulkarni, R. G., Garige, A. K., Nerella, S. G. & Garlapati, A. (2017). Synthesis and Cytotoxic Activity of New Chalcones and their Flavonol Derivatives. Med Chem, 7 (11), 353-360. DOI: 10.4172/2161-0444.1000480

Marrelli, D., Polom, K., Manzoni, G., Morgagni, P., Baiocchi, G. L. & Roviello, F. (2015). Multimodal treatment in gastric cancer. WJG, 21(26), 7954-7969. DOI:10.3748/wjg.v21.i26.7954

Marquina, S., Maldonado-Santiago, M., Sanchez-Carranza, J. N., Antunez-Mojica, M., Gonzalez-Mayal, Razo-Hernandez, R. S. & Alvarez L. (2019). Design, synthesis and QSAR study of 2′-hydroxy-4′-alkoxy chalcone derivatives that exert cytotoxic activity by the mitochondrial apoptotic pathway. Bioorg Med Chem, 27, 43–54. https://doi.org/10.1016/j.bmc.2018.10.045

Modzelewska, A., Pettit, C., Achatanta, G., Davidson, N. E., Huang, P., Khan, S. R. (2006). Anticancer activities of novel chalcone and bis-chalcone derivatives. Bioorganic & Medicinal Chemistry, 14, 3491-3495. DOI: 10.1016/j.bmc.2006.01.003

Mosmann, T. (1983). Rapid colorimetry assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55-63.

Orditura, M., Galizia, G., Sforza, V., Gambardella, V., Fabozzi, A., Laterza, M. M, Andreozzi, F., Ventriglia, J., Savastano, B., Mabilia, A., Lieto, E., Ciardiello, F., De Vita, F. (2014). Treatment of gastric câncer. WJG, 20(7), 1635-1649. doi:10.3748/wjg.v20.i7.1635

Orlikova, B., Tasdemir, D., Golais, F., Dicato, M. & Diederich, M. (2011). Dietary chalcones with chemopreventive and chemotherapeutic potential. Genes Nutr, 6, 125–147. DOI 10.1007/s12263-011-0210-5

Plummer, M., De Martel, C., Vignat, J., Ferlay, J., Bray, F. & Franceschi, S. Global burden of cancers attributable to infections in 2012. a synthetic analysis. (2016). The Lancet Glob Health, 4, 609-616. http://dx.doi.org/10.1016/S2214-109X(16)30143-7

Sharma, R., Kumar, R., Kodwani, R., Kapoor, S., Khare, A., Bansal, R., Khurana, S., Singh, S., Thomas, J., Roy, B., Phartyal, R., Saluja, S., Kumar, S. (2016). A Review on Mechanisms of Anti Tumor Activity of Chalcones. Anti-Cancer Agents Med Chem, 16(2), 200-211. DOI: 10.2174/1871520615666150518093144

Sandhar, H. K., Kumar, B., Prasher, S., Tiwari, P., Salhan, M. & Sharma, P. (2011). A Review of Phytochemistry and Pharmacology of Flavonoids. J Pharm Sci, 1, 25-41.

Santos, M. B., Anselmo, D. B., Oliveira, J. G., Jardim-Perassi, B. V., Monteiro, D. A., Silva, G., Gomes, E., Fachin, A. L., Marins, M., Zuccari, D. A. P. C. & Regasini, L. O. (2019). Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells. J Enzyme Inhib Med Chem, 34, 1093–1099. DOI: 10.1080/14756366.2019.1615485

Suwito, H., Jumina, Mustofa, Pudjiastuti, P., Fanani, M. Z., Kimata-Ariga, Y., Katahira, R., Kawakami, T., Fujiwara, T., Hase, T., Sirat, H. M. And Puspaningsih, N. N. T. (2014). Design and Synthesis of Chalcone Derivatives as Inhibitors of the Ferredoxin — Ferredoxin-NADP+ Reductase Interaction of Plasmodium falciparum: Pursuing New Antimalarial Agents. Molecules, 19, 21473-21488. DOI:10.3390/molecules191221473

Syam, S., Abdelwahab, S. I., Al-Mamary, M. A. And Mohan, S. (2012). Synthesis of Chalcones with Anticancer Activities. Molecules, 17, 6179-6195. DOI:10.3390/molecules17066179

Tomar, V., Bhatacharjee, G., Kamaluddin, Rajakumar, S., Srivastava, K. & Puri, S. K. (2010). Synthesis of new chalcone derivatives containing acridinyl moiety with potential antimalarial activity. Eur. j. med. Chem, 45, 745–751. DOI:10.1016/j.ejmech.2009.11.022

Ventura, T. L. B., Calixto, S. D., Abrahim-Vieira, B. A., Souza, A. M. T., Mello, M. V. P., Rodrigues, C. R., Miranda, L. S. M., Souza, R. O. M. A., Leal, I. C. R., Lasunskaia, E. B. & Muzitano, M. F. (2015). Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach. Molecules, 20, 8072-8093. DOI:10.3390/molecules20058072

Wang, T-Y, Li, Q. & Bi, K-S. (2018). Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian J Pharm, 13, 12-23. https://doi.org/10.1016/j.ajps.2017.08.004

WHO. 2018. International Agency for Research on Cancer. World Cancer Report: 2020. https://www.who.int/health-topics/cancer#tab=tab_1. Accessed July. 2020.

Wu, J., Li, J., Cai, Y., Pan, Y., Ye, F., Zhang, Y., Zhao, Y., Yang, S., Li, X. & Liang, G. (2011). Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents. J. Med. Chem, 5, 8110−8123. http://dx.doi.org/10.1021/jm200946h

Yadav, P., Lal, K., Kumar, A., Guru, S. K., Jaglan, S. & Bhushan, S. (2017). Green synthesis and anticancer potential of chalcone linked-1,2,3-triazoles. Eur. j. med. Chem, 126, 944-953. http://dx.doi.org/10.1016/j.ejmech.2016.11.030

Zhang, H., Jin, H., Ji, L-Z.., Tao, K., Liu, W., Zhao, H-Y. & Hou, T-P. (2011). Design, Synthesis, and Bioactivities Screening of a Diaryl Ketone-Inspired Pesticide Molecular Library as Derived from Natural Products. Chem Biol Drug Des, 78, 94–100. DOI: 10.1111/j.1747-0285.2011.01082.x.

Síntesis y evaluación biológica de chalconas y derivados in vitro frente a células AGP01

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