Generic placeholder image

Letters in Drug Design & Discovery

Author(s): Ashraf Hassan Fekry Abdelwahab* and Salma Ashraf Hassan Fekry

DOI: 10.2174/1570180819666220811102040

DownloadDownload PDF Flyer Cite As
Anti-cancerous Properties of the Synthesized Substituted Chromene Compounds and their Pharmacological Activities

Page: [1098 - 1106] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Introduction: 2-Amino-7-hydroxy-4-phenyl-4H-chromene-3-carbonitrile (4) was synthesized through a three-component reaction in ethanol/piperidine solution.

Methods: Synthesis of several new 4H-chromenes (5-14) has been achieved involving various reactions. The structure of these new compounds was confirmed using IR, 1H NMR and 13C NMR, as well as MS spectroscopy.

Results and Conclusion: All newly substituted chromene derivatives displayed potential analgesic and anticonvulsant activities. The structure-activity relationship study revealed that 2-amino-4-phenyl-3-(1Htetrazol- 5-yl)-4H-chromen-7-ol (13) was more beneficial than 8-hydroxy-2-methyl-5-phenyl-3,5-dihydro- 4H-chromeno[2,3-d]pyrimidin-4-one (11), 8-hydroxy-2,5-diphenyl-3,5-dihydro-4H-chromeno[2,3-d]pyrimidin- 4-one (12), and 8-hydroxy-5-phenyl-3,5-dihydro-4H-chromeno[2,3-d]pyrimidin-4-one (14) in terms of analgesic and anti-inflammatory activities.

Keywords: Analgesic, resorcinol, benzaldehyde, hydrazine hydrate, aromatic aldehydes, anti-inflammatory activity.

Graphical Abstract

[1]
Ren, Q.; Siau, W-Y.; Du, Z.; Zhang, K.; Wang, J. Expeditious assembly of a 2-amino-4H-chromene skeleton by using an enantioselective Mannich intramolecular ring cyclization-tautomerization cascade sequence. Chemistry, 2011, 17(28), 7781-7785.
[http://dx.doi.org/10.1002/chem.201100927] [PMID: 21618299]
[2]
Gourdeau, H.; Leblond, L.; Hamelin, B.; Desputeau, C.; Dong, K.; Kianicka, I.; Custeau, D.; Boudreau, C.; Geerts, L.; Cai, S.X.; Drewe, J.; Labrecque, D.; Kasibhatla, S.; Tseng, B. Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents. Mol. Cancer Ther., 2004, 3(11), 1375-1384.
[PMID: 15542776]
[3]
Sangani, C.B.; Shah, N.M.; Patel, M.P.; Patel, R.G. Microwave assisted synthesis of novel 4H-chromene derivatives bearing phenoxypyrazole and their antimicrobial activity assess. J. Serb. Chem. Soc., 2012, 77(9), 1165-1174.
[http://dx.doi.org/10.2298/JSC120102030S]
[4]
Mladenović, M.; Mihailović, M.; Bogojević, D.; Matić, S.; Nićiforović, N.; Mihailović, V.; Vuković, N.; Sukdolak, S.; Solujić, S. In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies. Int. J. Mol. Sci., 2011, 12(5), 2822-2841.
[http://dx.doi.org/10.3390/ijms12052822] [PMID: 21686153]
[5]
Cheng, J-F.; Ishikawa, A.; Ono, Y.; Arrhenius, T.; Nadzan, A. Novel chromene derivatives as TNF-α inhibitors. Bioorg. Med. Chem. Lett., 2003, 13(21), 3647-3650.
[http://dx.doi.org/10.1016/j.bmcl.2003.08.025] [PMID: 14552749]
[6]
Thareja, S.; Verma, A.; Kalra, A.; Gosain, S.; Rewatkar, P.V.; Kokil, G.R. Novel chromeneimidazole derivatives as antifungal compounds: Synthesis and in vitro evaluation. Acta Pol. Pharm., 2010, 67(4), 423-427.
[PMID: 20635539]
[7]
Jain, N.; Xu, J.; Kanojia, R.M.; Du, F.; Jian-Zhong, G.; Pacia, E.; Lai, M-T.; Musto, A.; Allan, G.; Reuman, M.; Li, X.; Hahn, D.; Cousineau, M.; Peng, S.; Ritchie, D.; Russell, R.; Lundeen, S.; Sui, Z. Identification and structure-activity relationships of chromene-derived selective estrogen receptor modulators for treatment of postmenopausal symptoms. J. Med. Chem., 2009, 52(23), 7544-7569.
[http://dx.doi.org/10.1021/jm900146e] [PMID: 19366247]
[8]
Mori, J.; Iwashima, M.; Takeuchi, M.; Saito, H. A synthetic study on antiviral and antioxidative chromene derivative. Chem. Pharm. Bull. (Tokyo), 2006, 54(3), 391-396.
[http://dx.doi.org/10.1248/cpb.54.391] [PMID: 16508200]
[9]
Patil, S.A.; Wang, J.; Li, X.S.; Chen, J.; Jones, T.S.; Hosni-Ahmed, A.; Patil, R.; Seibel, W.L.; Li, W.; Miller, D.D. New substituted 4H-chromenes as anticancer agents. Bioorg. Med. Chem. Lett., 2012, 22(13), 4458-4461.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.074] [PMID: 22608389]
[10]
Al-Masoudi, N.A.; Mohammed, H.H.; Hamdy, A.M.; Akrawi, O.A.; Eleya, N.; Spannenberg, A.; Pannecouque, C.; Langer, P. Synthesis and Anti-HIV Activity of New Fused Chromene Derivatives Derived from 2-Amino-4-(1-Naphthyl)-5-Oxo-4H,5H-Pyrano[3,2-c]Chromene-3-Carbonitrile. Z. Naturforsch. B. J. Chem. Sci., 2013, 68(3), 229-238.
[http://dx.doi.org/10.5560/znb.2013-2297]
[11]
Kamdar, N.R.; Haveliwala, D.D.; Mistry, P.T.; Patel, S.K. Synthesis and evaluation of in vitro antitubercular activity and antimicrobial activity of some novel 4H-chromeno[2,3-d]pyrimidine via 2-amino-4-phenyl-4H-chromene-3-carbonitriles. Med. Chem. Res., 2011, 20(7), 854-864.
[http://dx.doi.org/10.1007/s00044-010-9399-x]
[12]
Naseer, M.A.; Husain, A. Studies on chromene based 2, 6-disubstituted-thiazolo [3,2-B] [1,2,4] triazole derivatives: Synthesis and biological evaluation. J. Drug Deliv. Ther., 2019, 9(3-s), 236-242.
[13]
Bhat, M.A.; Siddiqui, N.; Khan, S.A. Synthesis of novel 3-(4-acetyl-5H/methyl-5-substituted phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromen-2-ones as potential anticonvulsant agents. Acta Pol. Pharm., 2008, 65(2), 235-239.
[PMID: 18666431]
[14]
Mohammed, A.; Makia, R.; Ali, M.; Raheem, R.; Yousif, E. Cytotoxic effects of valsartan organotin(IV) complexeson human lung cancer cells. Biointerface Res. Appl. Chem., 2021, 11(1), 8156-8816.
[15]
Hassan, F.; El-Hiti, G.A.; Abd-Allateef, M.; Yousif, E. Cytotoxicity anticancer activities of anastrozole against breast, liver hepatocellular, and prostate cancer cells. Saudi Med. J., 2017, 38(4), 359-365.
[http://dx.doi.org/10.15537/smj.2017.4.17061] [PMID: 28397941]
[16]
El-Agrody, A.; Abd El-Latif, M.; El-Hady, N.; Fakery, A.; Bedair, A. Heteroaromatization with 4-Hydroxycoumarin Part II: Synthesis of Some New Pyrano[2,3-d]Pyrimidines, [1,2,4]Triazolo[1,5-c]Pyrimidines and Pyrimido[1,6-b]-[1,2,4]Triazine Derivatives. Molecules, 2001, 6(6), 519-527.
[http://dx.doi.org/10.3390/60600519]
[17]
Bedair, A.H.; El-Hady, N.A.; El-Latif, A.; Fakery, A.H.; El-Agrody, A.M. 4-Hydroxycoumarin in heterocyclic synthesis. Part III. Synthesis of some new pyrano[2,3-d]pyrimidine, 2-substitute. Farmaco, 2000, 55(11-12), 708-714.
[http://dx.doi.org/10.1016/S0014-827X(00)00097-5] [PMID: 11204946]
[18]
Aragade, P.; Maddi, V.; Khode, S.; Palkar, M.; Ronad, P.; Mamledesai, S.; Satyanarayana, D. Synthesis and antibacterial activity of a new series of 3-[3-(substituted phenyl)-1-isonicotinoyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives. Arch. Pharm. (Weinheim), 2009, 342(6), 361-366.
[http://dx.doi.org/10.1002/ardp.200800156] [PMID: 19475595]
[19]
Abd El-Wahab, A.H.F. Synthesis, reactions and evaluation of the antimicrobial activity of some 4-(p-Halophenyl)-4H-naphthopyran, Pyranopyrimidine and Pyranotriazolopyrimidine Derivatives. Pharmaceuticals (Basel), 2012, 5(7), 745-757.
[http://dx.doi.org/10.3390/ph5070745] [PMID: 24281710]
[20]
Bedair, A.H.; Emam, H.A.; El-Hady, N.A.; Ahmed, K.A.; El-Agrody, A.M. Synthesis and antimicrobial activities of novel naphtho[2,1-b]pyran, pyrano[2,3-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[2,3-c]-pyrimidine derivatives. Farmaco, 2001, 56(12), 965-973.
[http://dx.doi.org/10.1016/S0014-827X(01)01168-5] [PMID: 11829118]
[21]
Khafagy, M.M.; Abd el-Wahab, A.H.F.; Eid, F.A.; el-Agrody, A.M. Synthesis of halogen derivatives of benzo[h]chromene and benzo[a]anthracene with promising antimicrobial activities. Farmaco, 2002, 57(9), 715-722.
[http://dx.doi.org/10.1016/S0014-827X(02)01263-6] [PMID: 12385521]
[22]
Radini, I.A.; Abd El-Wahab, A.H.F. Heteroaromatization with 4-Phenyldiazenyl-1-Naphthol. Part I: Synthesis of Some New Naphthopyrans and Naphthopyranopyrimidines. Eur. J. Chem., 2016, 7(2), 230-237.
[http://dx.doi.org/10.5155/eurjchem.7.2.230-237.1432]
[23]
Radini, I.A.; Mohamed, H.M.; Abd El-Wahab, A.H.F.; Kharir, M.A.Y. Heteroaromatization With 4-Phenyldiazenyl-1-Naphthol. Part II: Synthesis of Some New Benzochromens, Benzochromenopyrimidines, Benzochromenotriazolopyrimidines, Benzochromenopyrimidotriazepine and Antimicrobial Activities. Eur. J. Chem., 2017, 8(3), 240-247.
[http://dx.doi.org/10.5155/eurjchem.8.3.240-247.1599]
[24]
Mohamed, H.M.; Abd El-Wahab, A.H.F. Heteroaromatization with 4-Phenyldiazenyl-1-naphthol. Part IV: Synthesis of Some New Heterocyclic Compounds with Potential Biological Activity. Curr. Org. Synth., 2019, 16(6), 931-938.
[http://dx.doi.org/10.2174/1570179416666190719101727] [PMID: 31984914]
[25]
Kidwai, M.; Saxena, S.; Khan, M.K.; Thukral, S.S. Aqua mediated synthesis of substituted 2-amino-4H-chromenes and in vitro study as antibacterial agents. Bioorg. Med. Chem. Lett., 2005, 15(19), 4295-4298.
[http://dx.doi.org/10.1016/j.bmcl.2005.06.041] [PMID: 16040241]
[26]
Gilman, J. Canadian Council on Animal Care. Guide to the Care and Use of Experimental Animals, 2nd ed; Canadian Council on Animal Care: Ottawa, ON, Canada, 1984, Vol. I-II, .
[27]
Winter, C.A.; Risley, E.A.; Nuss, G.W. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc. Soc. Exp. Biol. Med., 1962, 111(3), 544-547.
[http://dx.doi.org/10.3181/00379727-111-27849] [PMID: 14001233]
[28]
Adeyemi, O.O.; Okpo, S.O.; Okpaka, O. The analgesic effect of the methanolic extract of Acanthus montanus. J. Ethnopharmacol., 2004, 90(1), 45-48.
[http://dx.doi.org/10.1016/j.jep.2003.09.021] [PMID: 14698507]
[29]
Cioli, V.; Putzolu, S.; Rossi, V.; Scorza Barcellona, P.; Corradino, C. The role of direct tissue contact in the production of gastrointestinal ulcers by anti-inflammatory drugs in rats. Toxicol. Appl. Pharmacol., 1979, 50(2), 283-289.
[http://dx.doi.org/10.1016/0041-008X(79)90153-4] [PMID: 505458]