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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Research Article

Synthesis and Characterisation of Flavonoid Mannich Bases and the Evaluation of their Cytotoxic Activity

Author(s): Chew-Cheen Chang*, Kooi-Mow Sim, Tuck-Meng Lim, Mallikarjuna Rao Pichika and Kit- Kay Mak

Volume 21, Issue 1, 2024

Published on: 12 September, 2023

Page: [77 - 88] Pages: 12

DOI: 10.2174/1570178620666230726144830

Price: $65

Abstract

With multi-drug-resistant tumours continuously evolving, developing new drugs with enhanced efficacy is essential. This study aims to synthesise flavonoid Mannich bases and evaluate their cytotoxic activity. The flavonoids isolated from the leaves of Muntingia calabura were used as reactants for the synthesis. Twenty flavonoid Mannich bases were synthesised via the Mannich reaction. Cytotoxic activity of the parent compounds and synthesised compounds were evaluated against two breast cancer cell lines, i.e., MCF-7, MDA-MB-231, and one normal breast cell line, MCF-10A, via MTT assay. Cytotoxic activity against the MDA-MB-231 cancer cell line showed that flavonoid Mannich bases exhibited greater activity than their parent compounds. 5,7-dihydroxy-8-(4- methoxybenzylamine)-2-phenyl-4H-chromen-4-one (4f) showed the highest cytotoxic activity against MDA-MB-231 cell with IC50 of 5.75±0.82 μM. For the MCF-7 cell line, the parent compounds and Mannich bases showed moderate activity with the IC50 range of 9.17-68.5 μM. For cytotoxic activity against the MCF-10A cell line, the parent compound, 5,7-dihydroxyflavone (4), showed the highest toxicity against MCF-10A with IC50 of 10.55±1.05 μM. The results suggest synthetic modifications have produced compounds with improved anticancer activity and selectivity against breast cancer cells.

Keywords: Flavonoids, Muntingia calabura, mannich reaction, 5, 7-dihydroxy-8-(4-methoxybenzylamine)-2-phenyl-4Hchromen- 4-one, cytotoxic activity, breast cancer cell lines.

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[1]
Peña-Morán, O.A.; Villarreal, M.L.; Álvarez-Berber, L.; Meneses-Acosta, A.; Rodríguez-López, V. Molecules, 2016, 21.
[2]
Xu, T.; Zheng, Z.; Guo, Y.; Bai, L.P. Eur. J. Med. Chem., 2020, 205.
[3]
Ouyang, Y.; Li, J.; Chen, X.; Fu, X.; Sun, S.; Wu, Q. Biomolecules, 2021, 11(6), 894-930.
[http://dx.doi.org/10.3390/biom11060894] [PMID: 34208562]
[4]
Newman, D.J.; Cragg, G.M. J. Nat. Prod., 2012, 75(3), 311-335.
[http://dx.doi.org/10.1021/np200906s] [PMID: 22316239]
[5]
Kanadaswami, C.; Lee, L.; Lee, P.H.; Hwang, J.; Huang, Y.; Lee, M. In vivo, 2005, 19, 895-910.
[6]
Tapas, A.R.; Sakarkar, D.M.; Kakde, R.B. Trop. J. Pharm. Res., 2008, 7(3), 1089-1099.
[http://dx.doi.org/10.4314/tjpr.v7i3.14693]
[7]
Ekalu, A.; Habila, J.D. Beni. Suef Univ. J. Basic Appl. Sci., 2020, 9, 1-14.
[http://dx.doi.org/10.1186/s43088-019-0027-7]
[8]
Mohammed, H.A.; Ba, L.A.; Burkholz, T.; Schumann, E.; Diesel, B.; Zapp, J.; Kiemer, A.K.; Ries, C.; Hartmann, R.W.; Hosny, M.; Jacob, C. Nat. Prod. Commun., 2011, 6, 31-34.
[PMID: 21366040]
[9]
Hoang, T.K.D.; Huynh, T.K.C.; Do, T.H.T.; Nguyen, T.D. Chem. Papers., 2018, 72, 1399-1406.
[10]
Nguyen, V.S.; Shi, L.; Luan, F.Q.; Wang, Q.A. Acta. Biochim. Pol., 2015, 62(3), 547-552.
[http://dx.doi.org/10.18388/abp.2015_992] [PMID: 26345098]
[11]
Liu, R.; Zhao, B.; Wang, D.E.; Yao, T.; Pang, L.; Tu, Q.; Ahmed, S.; Liu, J.J.; Wang, J. Molecules, 2012, 17(12), 14748-14764.
[http://dx.doi.org/10.3390/molecules171214748] [PMID: 23519250]
[12]
Yun, B.H.; Lee, Y.H.; Park, K.T.; Jung, S.J.; Lee, Y.S. Bioorg. Med. Chem. Lett., 2016, 26(17), 4170-4173.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.063] [PMID: 27503682]
[13]
Nor-Eljaleel, A.; Fadul, H.; Ayuob, S.; Karim, M.; Westhuizen, J.; Abualreish, M. Int. Res. J. Pure Appl. Chem., 2015, 5, 106-112.
[http://dx.doi.org/10.9734/IRJPAC/2015/13111]
[14]
Subramaniapillai, S.G. J. Chem. Sci., 2013, 125(3), 467-482.
[http://dx.doi.org/10.1007/s12039-013-0405-y]
[15]
Roman, G. Eur. J. Med. Chem., 2015, 89, 743-816.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.076] [PMID: 25462280]
[16]
Hieu, B.T.; Thuy, L.T.; Thuy, V.T.; Tien, H.X.; van Chinh, L.; Hoang, V.D.; Vu, T.K. Bull. Korean Chem. Soc., 2012, 33, 1586-1592.
[http://dx.doi.org/10.5012/bkcs.2012.33.5.1586]
[17]
Liu, H.; Huang, X.; Lou, D.; Liu, X.; Liu, W.; Wang, Q. Bioorg. Med. Chem. Lett., 2014, 24(19), 4749-4753.
[http://dx.doi.org/10.1016/j.bmcl.2014.07.087] [PMID: 25205193]
[18]
Lv, X.H.; Liu, H.; Ren, Z.L.; Wang, W.; Tang, F.; Cao, H.Q. Mol. Divers., 2019, 23(2), 299-306.
[http://dx.doi.org/10.1007/s11030-018-9873-9] [PMID: 30168050]
[19]
Mahmood, N.D.; Nasir, N.L.M.; Rofiee, M.S.; Tohid, S.F.M.; Ching, S.M.; Teh, L.K.; Salleh, M.Z.; Zakaria, Z.A. Pharm. Biol., 2014, 52(12), 1598-1623.
[http://dx.doi.org/10.3109/13880209.2014.908397] [PMID: 25068675]
[20]
Nshimo, C.M.; Pezzuto, J.M.; Kinghorn, A.D.; Farns Worth, N.R. Int. J. Pharmacol., 1993, 31, 77-81.
[21]
Chen, J.-J.; Lin, R.-W.; Duh, C.-Y.; Huang, H.-Y.; Chen, J.J.; Lin, R-W.; Duh, C-Y.; Huang, H-Y.; Chen, I-S. J. Chin. Chem. Soc., 2004, 51(3), 665-670.
[http://dx.doi.org/10.1002/jccs.200400100]
[22]
Su, B.N.; Parka, E.J.; Vigo, J.S.; Graham, J.G.; Cabieses, F.; Fong, H.H.S.; Pezzuto, J.M.; Kinghorn, A.D. Phytochemistry, 2003, 63, 335-341.
[http://dx.doi.org/10.1016/S0031-9422(03)00112-2] [PMID: 12737982]
[23]
Chen, J.J.; Lee, H.H.; Duh, C.Y.; Chen, I.S. Planta Med., 2005, 71(10), 970-973.
[http://dx.doi.org/10.1055/s-2005-871223] [PMID: 16254834]
[24]
Chen, J.-J.; Lee, H.-H.; Shih, C.-D.; Liao, C.-H.; Chen, I.-S.; Chou, T.-H. Planta Med., 2006, 73(6), 572-577.
[25]
Guo, Y.Q.; Tang, G.H.; Lou, L.L.; Li, W.; Zhang, B.; Liu, B.; Yin, S. Eur. J. Med. Chem., 2018, 144, 758-766.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.057] [PMID: 29291443]
[26]
Sufian, A.S.; Ramasamy, K.; Ahmat, N.; Zakaria, Z.A.; Yusof, M.I.M. J. Ethnopharmacol., 2013, 146, 198-204.
[http://dx.doi.org/10.1016/j.jep.2012.12.032] [PMID: 23276785]
[27]
Gul, H.I.; Yerdelen, K.O.; Gul, M.; Das, U.; Pandit, B.; Li, P.K.; Secen, H. Sahin. F. Arch. Pharm., 2007, 340, 195-201.
[28]
Bondarenko, S.P.; Frasinyuk, M.S. Chem. Nat. Compd., 2013, 49(5), 841-844.
[http://dx.doi.org/10.1007/s10600-013-0760-4]
[29]
Fu, L.; Mou, J.; Deng, Y.; Ren, X.; Qiu, S. Front Chem., 2022, 10, 1-16.

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