Mannich aminomethylation of flavonoids and anti-proliferative activity against breast cancer cell
Tóm tắt
We herein report Mannich aminomethylation of variously structural flavonoids and their biological evaluation against human breast cancer cell. Mannich reaction showed that substitution at C-6 position depends on amine basicity and C-ring feature of flavonoids. All five flavonoid substrates reacted with strong amine bases to afford the bis(6,8-aminomethyl) derivatives, while with weak amines, the different products were obtained dependently on structural characteristic of flavonoid. 3-OH and 3-O-substituted groups on the C-ring exhibited the deactivated aminomethylation at C-6 position, whereas substitution at this position was independent on bond feature at C-2 and C-3 on the C-ring. Screening anti-proliferative activity showed six flavonoids possessed activity against breast cancer cell, MDA-MB-231. Among them, the flavonoids, luteolin (2) and 3′,4′,5,7-tetrahydroxy-6,8-bis(pyrrolidin-1-ylmethyl)-3-rutinosylflavone (3a), displayed the highest anti-proliferative activity with the lowest IC50 values.
Tài liệu tham khảo
Babu TH, Rao VRS, Tiwari AK, Babu KS, Srinivas PV, Ali AZ, Rao JM (2008) Synthesis and biological evaluation of novel 8-aminomethylated oroxylin A analogues as α-glucosidase inhibitors. Bioorg Med Chem Lett 18:1659–6662. https://doi.org/10.1016/j.bmcl.2008.01.055
Buravlev EV, Shevchenko OG, Chukicheva IY, Kutchin AV (2017) Synthesis and membrane-protective properties of aminomethyl derivatives of quercetin at the C-8 position. Chem Pap. https://doi.org/10.1007/s11696-017-0272-y
Candiracci M, Piatti E, Dominguez-Barragan M, Garcia-Antras D, Morgado B, Ruano D, Gutierrez JF, Parrado J, Castano A (2012) Anti-inflammatory activity of a honey flavonoid extract on lipopolysaccharide-activated N13 microglial cells. J Agric Food Chem 60:12304–12311. https://doi.org/10.1021/jf302468h
Chahar MK, Sharma N, Dobhal MP, Joshi YC (2011) Flavonoids: a versatile source of anticancer drugs. Pharmacogn Rev 5:1–12. https://doi.org/10.4103/0973-7847.79093
Chen Y, Cass SL, Kutty SK, Yee EMH, Chan DSH, Gardner CR, Vittorio O, Pasquier E, Black DS, Kumar N (2015) Synthesis, biological evaluation and structure–activity relationship studies of isoflavene based Mannich bases with potent anti-cancer activity. Bioorg Med Chem Lett 25:5377–5383. https://doi.org/10.1016/j.bmcl.2015.09.027
Cottiglia F, Casu L, Bonsignore L, Casu M, Floris C, Sosa S, Altinier G, Loggia RD (2005) Topical anti-inflammatory activity of flavonoids and a new xanthone from Santolina insularis. Z Naturforsch 60c:63–66. https://doi.org/10.1515/znc-2005-1-212
Dang CH, Nguyen CH, Nguyen TD, Im C (2014) Synthesis and characterization of N-acyl-tetra-O-acyl glucosamine derivatives. RSC Adv 4:6239–6245. https://doi.org/10.1039/C3RA46007J
Dang CH, Le VD, Nguyen CH, Nguyen TD (2017) A facile synthesis of aggregation pheromones of Rhinoceros beetle and Rhychophorus weevil. ARKIVOC 2017; 2017(v):187–195. https://doi.org/10.24820/ark.5550190.p010.271
Denizot F, Lang R (1986) Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89:271–277. https://doi.org/10.1016/0022-1759(86)90368-6
Frasinyuk MS, Mrug GP, Bondarenko SP, Sviripa VM, Zhang W, Cai X, Fiandalo MV, Mohler JL, Liu C, Watt DS (2015) Application of Mannich bases to the synthesis of hydroxymethylated isoflavonoids as potential antineoplastic agents. Org Biomol Chem 13:11292–11301. https://doi.org/10.1039/c5ob01828e
Gorbunov EB, Rusinov GL, Ulomskii EN, Eltsov OS, Rusinov VL, Kartsev VG, Charushin VN, Khalymbadzha IA, Chupakhin ON (2016) Direct modification of quercetin by 6-nitroazolo[1,5-a]pyrimidines. Chem Nat Compd 52:708–710. https://doi.org/10.1007/s10600-016-1749-6
Ha L, Qian Y, Zhang S, Ju X, Sun S, Guo H, Wang Q, Li K, Fan Q, Zheng Y, Li H (2016) Synthesis and biological evaluation of scutellaria flavone cyclaneaminol Mannich base derivatives as novel CDK1 inhibitors. Anticancer Agents Med Chem 16:914–924. https://doi.org/10.2174/1871520615666150928114425
Helgen TR, Sciotti RJ, Lee P, Duffy S, Avery VM, Igbinoba O, Akoto M, Hagen TJ (2015) The synthesis, antimalarial activity and CoMFA analysis of novel aminoalkylated quercetin analogs. Bioorg Med Chem Lett 25:327–332. https://doi.org/10.1016/j.bmcl.2014.11.039
Hoang TKD, Huynh TKC, Nguyen TD (2015) Synthesis, characterization, anti-inflammatory and anti-proliferative activity against MCF-7 cells of O-alkyl and O-acyl flavonoid derivatives. Bioorg Chem 63:45–52. https://doi.org/10.1016/j.bioorg.2015.09.005
Kanadaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT, Lee MT (2005) The antitumor activities of flavonoids. In Vivo 19:895–910
Kaul TN, Middleton JMDE, Ogra PL (1985) Antiviral effect of flavonoids on human viruses. J Med Virol 15:71–79. https://doi.org/10.1002/jmv.1890150110
Kukhareva TS, Krasnova VA, Koroteev MP, Kaziev GZ, Kuleshova LN, Korlyukov AA, Antipin MY, Nifant’ev EE (2004) Electrophilic substitution in the dihydroquercetin system. Aminomethylation. Russ J Org Chem 40(8):1190–1193. https://doi.org/10.1023/B:RUJO.0000045904.63368.06
Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J. https://doi.org/10.1155/2013/162750 article ID 162750
Lee WJ, Chen WK, Wang CJ, Lin WL, Tseng TH (2008) Apigenin inhibits HGF promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells. Toxicol Appl Pharmacol 226:178–191. https://doi.org/10.1016/j.taap.2007.09.013
Lis R, Marisca AJ (1987) Methanesulfonanilides and the Mannich reaction. J Org Chem 52:4377–4379. https://doi.org/10.1021/jo00228a041
Ng TB, Huang B, Fong WP, Yeung HW (1997) Anti-human immunodeficiency virus (anti-HIV) natural products with special emphasis on HIV reverse transcriptase inhibitors. Life Sci 61:933–949. https://doi.org/10.1016/S0024-3205(97)00245-2
Nguyen TB, Wang Q, Gueritte F (2011) An efficient one-step synthesis of piperidin-2-yl and pyrrolidin-2-yl flavonoid alkaloids through phenolic Mannich reactions. Eur J Org Chem 2011:7076–7079. https://doi.org/10.1002/ejoc.201101312
Nguyen TD, Nguyen CH, Im C, Dang CH (2015a) Synthesis of corn rootworm pheromones from commercial diols. Chem Pap 69(2):380–384. https://doi.org/10.1515/chempap-2015-0027
Nguyen VS, Shi L, Luan FQ, Wang QA (2015b) Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines. Acta Biochim Pol 6:547–552. https://doi.org/10.18388/abp.2015_992
Nguyen TD, Nguyen CH, Im C, Dang CH (2016) A facile synthesis of sex pheromone of the Cabbage Looper, Trichoplusia ni. Chem Nat Compd 52(5):877–879. https://doi.org/10.1007/s10600-016-1800-7
Nguyen VS, Shi L, Wang SC, Wang QA (2017) Synthesis of icaritin and β-anhydroicaritin Mannich base derivatives and their cytotoxic activities on three human cancer cell lines. Anticancer Agents Med Chem 17:137–142. https://doi.org/10.2174/1871520616666160404111210
Nifant’ev EE, Mosyurov SE, Kukhareva TS, Vasyanina LK (2013) N, N’-diethyl-1,3-propanediamine in the dihydroquercetin aminomethylation reaction. Dokl Chem 451(2):197–200. https://doi.org/10.1134/S0012500813080016
Orhana DD, Ozcelik B, Ozgen S, Ergun F (2010) Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiol Res 165:496–504. https://doi.org/10.1016/j.micres.2009.09.002
Pan MH, Lai CS, Ho CT (2010) Anti-inflammatory activity of natural dietary flavonoids. Food Funct 1:15–31. https://doi.org/10.1039/C0FO00103A
Phromnoi K, Yodkeeree S, Anuchapreeda S, Limtrakul P (2009) Inhibition of MMP-3 activity and invasion of the MDAMB-231 human invasive breast carcinoma cell line by bioflavonoids. Acta Pharmacol Sin 30:1169–1176. https://doi.org/10.1038/aps.2009.107
Pietta PG (2000) Flavonoids as antioxidants. J Nat Prod 63:1035–1042. https://doi.org/10.1021/np9904509
Ravishankar D, Rajora AK, Greco F, Osborn HMI (2013) Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol 45:2821–2831. https://doi.org/10.1016/j.biocel.2013.10.004
Rice-Evans CA (2001) Flavonoid antioxidants. Curr Med Chem 8:797–807. https://doi.org/10.2174/0929867013373011
Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20:933–956. https://doi.org/10.1016/0891-5849(95)02227-9
Tempesti TC, Alvarez MG, Araujo MFD, Junior FEAC, de Carvalho MG, Durantini EN (2012) Antifungal activity of a novel quercetin derivative bearing a trifluoromethyl group on Candida albicans. Med Chem Res 21:2217–2222. https://doi.org/10.1007/s00044-011-9750-x
Tugrak M, Yamali C, Sakagami H, Gul HI (2015) Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities. J Enzyme Inhib Med Chem 31:818–823. https://doi.org/10.3109/14756366.2015.1070263
Vijayababu MR, Arunkumar A, Kanagaraj P, Venkataraman P, Krishnamoorthy G, Arunakaran J (2006) Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3). Mol Cell Biochem 287:109–116. https://doi.org/10.1007/s11010-005-9085-3
Yusakul G, Sakamoto S, Juengwatanatrakul T, Putalun W, Tanaka H, Morimoto S (2016) Preparation and application of a monoclonal antibody against the isoflavone glycoside daidzin using a Mannich reaction-derived hapten conjugate. Phytochem Anal 27:81–88. https://doi.org/10.1002/pca.2604
Zhang S, Ma J, Bao Y, Yang P, Zou L, Li K, Sun X (2008) Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: synthesis, SAR analysis, and biological activity. Bioorg Med Chem 16:7127–7132. https://doi.org/10.1016/j.bmc.2008.06.055
Zhurakulov SN, Babkin VA, Chernyak EI, Morozov SV, Grigor’ev IA, Levkovich MG, Vinogradova VI (2015) Aminomethylation of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines by dihydroquercetin. Chem Nat Compd 51(1):57–61. https://doi.org/10.1007/s10600-051-1203-1