Antioxidant, Antitumor and Bactericidal Activities of Ethyl Gallate Quinoxalines

Author(s): Rafaely N. Lima, Jaqueline R. Gonçalves, Valdenizia R. Silva, Luciano de S. Santos, Daniel P. Bezerra, Milena B.P. Soares, Andrei Leitão, André L.M. Porto*

Journal Name: Current Bioactive Compounds

Volume 16 , Issue 6 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Quinoxaline, a fused heterocycle of benzene and pyrazine rings are becoming recognized as a potent class of anti-cancer compounds, such as, in a wide array of pharmacological activities.

Methods: We evaluate the three gallate quinoxalines (G-A1, G-A2, and G-A3) as c-Met kinase inhibitors using a docking study, in vitro anticancer potential measurements, antioxidant and bactericidal activities.

Results: The docking study showed hydrogen bond linkage of quinoxalines with amino acids at active site of c-Met kinase structures, indicating a possible cancer inhibition cell proliferation. Therefore, the three quinoxalines were analyzed against four in vitro cancer cell lines, and G-A1 demonstrated cytotoxicity against HL-60 and HCT116 cell lines (IC50= 9.55 and IC50= 16.67 μmol L-1, respectively). In HepG2 and MCF-7 cells, the IC50 were 22.48 and 33.42 μmol L-1, respectively. For G-A2 and G-A3, cytotoxic activity ranged from 61.22 to >101.21 μmol L-1. Potent antioxidant activities were also obtained for G-A2>G-A1>G-A3 (IC50= 4.5-8.4 μmol L-1 and AAI= 8.8-17.8). Six different Bacillius strains showed growth inhibition (11.33 to 13.33 mm) in the presence of quinoxaline G-A1 (500 μg).

Conclusion: The present work showed the biological potential of quinoxalines G-A1, G-A2 and G-A3 in inhibiting four cancer cells proliferation, in addition to a very strong antioxidant activity.

Keywords: Antitumor, cytotoxicity, DPPH, disk-diffusion, gallic acid, docking study.

[1]
Abu-Hashem, A.A.; Gouda, M.A.; Badria, F.A. Synthesis of some new pyrimido[2′,1′:2,3]thiazolo[4,5-b]quinoxaline derivatives as anti-inflammatory and analgesic agents. Eur. J. Med. Chem., 2010, 45(5), 1976-1981.
[http://dx.doi.org/10.1016/j.ejmech.2010.01.042] [PMID: 20149490]
[2]
Moreno, E.; Ancizu, S.; Pérez-Silanes, S.; Torres, E.; Aldana, I.; Monge, A. Synthesis and antimycobacterial activity of new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives. Eur. J. Med. Chem., 2010, 45(10), 4418-4426.
[http://dx.doi.org/10.1016/j.ejmech.2010.06.036] [PMID: 20656380]
[3]
Das, U.; Das, S.; Bandy, B.; Gorecki, D.K.J.; Dimmock, J.R. E-2-[3-(3,4-dichlorophenyl)-1-oxo-2-propenyl]-3-methylquinoxaline-1,4-dioxide: A lead antitubercular agent which alters mitochondrial respiration in rat liver. Eur. J. Med. Chem., 2010, 45(10), 4682-4686.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.030] [PMID: 20705367]
[4]
Tanis, S.P.; Strohbach, J.W.; Parker, T.T.; Moon, M.W.; Thaisrivongs, S.; Perrault, W.R.; Hopkins, T.A.; Knechtel, M.L.; Oien, N.L.; Wieber, J.L.; Stephanski, K.J.; Wathen, M.W. The design and development of 2-aryl-2-hydroxy ethylamine substituted 1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamides as inhibitors of human cytomegalovirus polymerase. Bioorg. Med. Chem. Lett., 2010, 20(6), 1994-2000.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.094] [PMID: 20167488]
[5]
Manta, S.; Gkaragkouni, D-N.; Kaffesaki, E.; Gkizis, P.; Hadjipavlou-Litina, D.; Pontiki, E.; Balzarini, J.; Dehaen, W.; Komiotis, D. A novel and easy two-step, microwave-assisted method for the synthesis of halophenyl pyrrolo[2,3-b]quinoxalines via their pyrrolo precursors. Evaluation of their bioactivity. Tetrahedron Lett., 2014, 55, 1873-1876.
[http://dx.doi.org/10.1016/j.tetlet.2014.01.106]
[6]
Shibinskaya, M.O.; Lyakhov, S.A.; Mazepa, A.V.; Andronati, S.A.; Turov, A.V.; Zholobak, N.M.; Spivak, N.Y. Synthesis, cytotoxicity, antiviral activity and interferon inducing ability of 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxalines. Eur. J. Med. Chem., 2010, 45(3), 1237-1243.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.014] [PMID: 20056519]
[7]
Duque-Montaño, B.E.; Gómez-Caro, L.C.; Sanchez-Sanchez, M.; Monge, A.; Hernández-Baltazar, E.; Rivera, G.; Torres-Angeles, O. Synthesis and in vitro evaluation of new ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide against Entamoeba histolytica. Bioorg. Med. Chem., 2013, 21(15), 4550-4558.
[http://dx.doi.org/10.1016/j.bmc.2013.05.036] [PMID: 23787289]
[8]
Barea, C.; Pabón, A.; Castillo, D.; Zimic, M.; Quiliano, M.; Galiano, S.; Pérez-Silanes, S.; Monge, A.; Deharo, E.; Aldana, I. New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities. Bioorg. Med. Chem. Lett., 2011, 21(15), 4498-4502.
[http://dx.doi.org/10.1016/j.bmcl.2011.05.125] [PMID: 21724395]
[9]
Ronga, L.; Del Favero, M.; Cohen, A.; Soum, C.; Le Pape, P.; Savrimoutou, S.; Pinaud, N.; Mullié, C.; Daulouede, S.; Vincendeau, P.; Farvacques, N.; Agnamey, P.; Pagniez, F.; Hutter, S.; Azas, N.; Sonnet, P.; Guillon, J. Design, synthesis and biological evaluation of novel 4-alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents-part III. Eur. J. Med. Chem., 2014, 81, 378-393.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.037] [PMID: 24858543]
[10]
Patel, N.B.; Patel, J.N.; Purohit, A.C.; Patel, V.M.; Rajani, D.P. MooPuc, R.; Lopez-Cedillo, J.C.; Nogueda-Torres, B.; Rivera, G. In vitro and in vivo assessment of newer quinoxaline-oxadiazole hybrids as antimicrobial and antiprotozoal agents. Int. J. Antimicrob. Agents, 2017, 50(3), 413-418.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.04.016] [PMID: 28687457]
[11]
Sangilipandi, S.; Sutradhar, D.; Bhattacharjee, K.; Kaminsky, W.; Joshi, S.R.; Chandra, A.K.; Rao, K.M. Synthesis, structure, antibacterial studies and DFT calculations of arene ruthenium, Cp*Rh, Cp*Ir and tricarbonylrhenium metal com-plexes containing 2-chloro-3-(3-(2-pyridyl)pyrazolyl)quinoxaline ligand. Inorg. Chim. Acta, 2016, 441, 95-108.
[http://dx.doi.org/10.1016/j.ica.2015.11.012]
[12]
Ishikawa, H.; Sugiyama, T.; Kurita, K.; Yokoyama, A. Synthesis and antimicrobial activity of 2,3-bis(bromomethyl)quinoxaline derivatives. Bioorg. Chem., 2012, 41-42, 1-5.
[http://dx.doi.org/10.1016/j.bioorg.2011.12.002] [PMID: 22245018]
[13]
Gopi, C.; Sastry, V.G.; Dhanaraju, M.D. Microwave-assisted synthesis, structural activity relationship and biological activity of some new quinoxaline Schiff base derivatives as highly potent spirochete bactericidal agents. Beni-Suef. Univ. J. Basic Appl. Sci., 2017, 6, 39-47.
[14]
Pereira, J.A.; Pessoa, A.M.; Cordeiro, M.N.D.S.; Fernandes, R.; Prudêncio, C.; Noronha, J.P.; Vieira, M. Quinoxaline, its derivatives and applications: A State of the Art review. Eur. J. Med. Chem., 2015, 97, 664-672.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.058] [PMID: 25011559]
[15]
Subran, K.S.; Paira, P. Synthesis and pharmacological applications of certain quinoxaline analogues: A review. Curr. Bioact. Compd., 2017, 13, 186-212.
[http://dx.doi.org/10.2174/1573407213666161108102411]
[16]
da Costa, C.F.; de Souza, M.V.N.; Gomes, C.R.B.; Facchinetti, V. Microwave-assisted synthesis of quinoxalines - A review. Curr. Microw. Chem., 2017, 4, 277-286.
[17]
Han, Y.T.; Jung, J-W.; Kim, N-J. Recent advances in the synthesis of biologically active cinnoline, phthalazine and quinoxaline derivatives. Curr. Org. Chem., 2017, 21, 1265-1291.
[http://dx.doi.org/10.2174/1385272821666170221150901]
[18]
de Andrade, V.S.C.; de Mattos, M.C.S. N-Halo reagents-mediated greener protocols for heterocyclic synthesis: Safe chemistry and pot-economy approaches to azoles and quinoxalines. Curr. Green Chem., 2018, 5, 67-84.
[http://dx.doi.org/10.2174/2452273202666180719124023]
[19]
Andrés, J-I.; Buijnsters, P.; De Angelis, M.; Langlois, X.; Rombouts, F.; Trabanco, A.A.; Vanhoof, G. Discovery of a new series of [1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(3), 785-790.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.077] [PMID: 23260348]
[20]
Loch-Neckel, G.; Bicca, M.A.; Leal, P.C.; Mascarello, A.; Siqueira, J.M.; Calixto, J.B. In vitro and in vivo anti-glioma activity of a chalcone-quinoxaline hybrid. Eur. J. Med. Chem., 2015, 90, 93-100.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.014] [PMID: 25461314]
[21]
Briguglio, I.; Loddo, R.; Laurini, E.; Fermeglia, M.; Piras, S.; Corona, P.; Giunchedi, P.; Gavini, E.; Sanna, G.; Giliberti, G.; Ibba, C.; Farci, P.; La Colla, P.; Pricl, S.; Carta, A. Synthesis, cytotoxicity and antiviral evaluation of new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives. Eur. J. Med. Chem., 2015, 105, 63-79.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.002] [PMID: 26479028]
[22]
Patel, S.B.; Patel, B.D.; Pannecouque, C.; Bhatt, H.G. Synthesis, cytotoxicity and antiviral evaluation of new series of im-idazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone deriv-atives. Eur. J. Med. Chem., 2016, 117, 230-240.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.019] [PMID: 27105027]
[23]
Park, K.L.; Ko, N.Y.; Lee, J.H.; Kim, D.K.; Kim, H.S.; Kim, A-R.; Her, E.; Kim, B.; Kim, H.S.; Moon, E-Y.; Kim, Y.M.; Kim, H-R.; Choi, W.S. 4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice. Toxicol. Appl. Pharmacol., 2011, 257(2), 235-241.
[http://dx.doi.org/10.1016/j.taap.2011.09.009] [PMID: 21958720]
[24]
Ibrahim, M.K.; Eissa, I.H.; Abdallah, A.E.; Metwaly, A.M.; Radwan, M.M.; ElSohly, M.A. Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of novel quinoxaline derivatives as potential PPARγ and SUR agonists. Bioorg. Med. Chem., 2017, 25(4), 1496-1513.
[http://dx.doi.org/10.1016/j.bmc.2017.01.015] [PMID: 28117121]
[25]
Ibrahim, M-K.; Abd-Elrahman, A.A.; Ayyad, R.R.A.; El-Adl, K.; Mansour, A.M.; Eissa, I.H. Design and synthesis of some novel 2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)-N-(4-(substituted)phenyl)acetamide derivatives for biological evaluation as anticonvulsant agents. Bull. Fac. Pharm. Cairo Univ., 2013, 51, 101-111.
[http://dx.doi.org/10.1016/j.bfopcu.2012.11.003]
[26]
Kim, K-H.; Maderna, A.; Schnute, M.E.; Hegen, M.; Mohan, S.; Miyashiro, J.; Lin, L.; Li, E.; Keegan, S.; Lussier, J.; Wrocklage, C.; Nickerson-Nutter, C.L.; Wittwer, A.J.; Soutter, H.; Caspers, N.; Han, S.; Kurumbail, R.; Dunussi-Joannopoulos, K.; Douhan, J., III; Wissner, A. Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of rheumatoid arthritis. Bioorg. Med. Chem. Lett., 2011, 21(21), 6258-6263.
[http://dx.doi.org/10.1016/j.bmcl.2011.09.008] [PMID: 21958547]
[27]
Galal, S.A.; Abdelsamie, A.S.; Soliman, S.M.; Mortier, J.; Wolber, G.; Ali, M.M.; Tokuda, H.; Suzuki, N.; Lida, A.; Ramadan, R.A.; El Diwani, H.I. Design, synthesis and structure-activity relationship of novel quinoxaline derivatives as cancer chemopreventive agent by inhibition of tyrosine kinase receptor. Eur. J. Med. Chem., 2013, 69, 115-124.
[http://dx.doi.org/10.1016/j.ejmech.2013.07.049] [PMID: 24013411]
[28]
Ismail, M.M.F.; Amin, K.M.; Noaman, E.; Soliman, D.H.; Ammar, Y.A. New quinoxaline 1, 4-di-N-oxides: Anticancer and hypoxia-selective therapeutic agents. Eur. J. Med. Chem., 2010, 45(7), 2733-2738.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.052] [PMID: 20236735]
[29]
Rodrigues, F.A.R. Bomfim, Ida.S.; Cavalcanti, B.C.; Pessoa, Cdo.Ó.; Wardell, J.L.; Wardell, S.M.S.V.; Pinheiro, A.C.; Kaiser, C.R.; Nogueira, T.C.M.; Low, J.N.; Gomes, L.R.; de Souza, M.V.N. Design, synthesis and biological evaluation of (E)-2-(2-arylhydrazinyl)quinoxalines, a promising and potent new class of anticancer agents. Bioorg. Med. Chem. Lett., 2014, 24(3), 934-939.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.074] [PMID: 24398294]
[30]
Chemler, S.R. Phenanthroindolizidines and phenanthroquino-lizidines: Promising alkaloids for anti-cancer therapy. Curr. Bioact. Compd., 2009, 5(1), 2-19.
[http://dx.doi.org/10.2174/157340709787580928] [PMID: 20160962]
[31]
Petronijevic, J.; Jankovic, N.; Bugarcic, Z. Synthesis of quinoxa-line-based compounds and their antitumor and antiviral po-tentials. Mini Rev. Org. Chem., 2018, 15, 220-226.
[http://dx.doi.org/10.2174/1570193X14666171201143357]
[32]
Parrino, B.; Carbone, A.; Spanò, V.; Montalbano, A.; Giallombardo, D.; Barraja, P.; Attanzio, A.; Tesoriere, L.; Sissi, C.; Palumbo, M.; Cirrincione, G.; Diana, P. Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity. Eur. J. Med. Chem., 2015, 94, 367-377.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.009] [PMID: 25778992]
[33]
Lima, R.N.; Porto, A.L.M. Facile synthesis of new quinoxa-lines from ethyl gallate by green chemistry protocol. Tetrahedron Lett., 2017, 58, 825-828.
[http://dx.doi.org/10.1016/j.tetlet.2016.12.062]
[34]
OpenEye Scientific Software. http://www.eyesopen.com
[35]
Hawkins, P.C.D.; Skillman, A.G.; Warren, G.L.; Ellingson, B.A.; Stahl, M.T. Conformer generation with OMEGA: algorithm and validation using high quality structures from the Protein Databank and Cambridge Structural Database. J. Chem. Inf. Model., 2010, 50(4), 572-584.
[http://dx.doi.org/10.1021/ci100031x] [PMID: 20235588]
[36]
McGann, M. FRED pose prediction and virtual screening accuracy. J. Chem. Inf. Model., 2011, 51(3), 578-596.
[http://dx.doi.org/10.1021/ci100436p] [PMID: 21323318]
[37]
McGann, M. FRED and HYBRID docking performance on standardized datasets. J. Comput. Aided Mol. Des., 2012, 26(8), 897-906.
[http://dx.doi.org/10.1007/s10822-012-9584-8] [PMID: 22669221]
[38]
Boulevard, U.; Manassas, V. American Type Culture Collection (ATCC), https://www.atcc.org/
[39]
Lima, R.N.; Silva, V.R.; Santos, L.S.; Bezerra, D.P.; Soares, M.B.P.; Porto, A.L.M. Fast synthesis of amides from ethyl salicylate under microwave radiation in a solvent-free system. RSC Adv., 2017, 7, 56566-56574.
[http://dx.doi.org/10.1039/C7RA11434F]
[40]
Sharma, O.P.; Bhat, T.K. DPPH antioxidant assay revisited. Food Chem., 2009, 113, 1202-1205.
[http://dx.doi.org/10.1016/j.foodchem.2008.08.008]
[41]
Melagraki, G.; Afantitis, A.; Igglessi-Markopoulou, O.; Detsi, A.; Koufaki, M.; Kontogiorgis, C.; Hadjipavlou-Litina, D.J. Synthesis and evaluation of the antioxidant and anti-inflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts. Eur. J. Med. Chem., 2009, 44(7), 3020-3026.
[http://dx.doi.org/10.1016/j.ejmech.2008.12.027] [PMID: 19232783]
[42]
Scherer, R.; Godoy, H.T. Antioxidant activity index (AAI) by the 2,2-diphenyl-1-picrylhydrazyl method. Food Chem., 2009, 112, 654-658.
[http://dx.doi.org/10.1016/j.foodchem.2008.06.026]
[43]
Meira, E.B.; dos Anjos, C.S.; Birolli, W.G.; Peret, M.C.M.; Fonseca, L.P.; Nitschke, M.; Sakamoto, I.K.; Varesche, M.B.A.; Porto, A.L.M. Isolation of Bacteria from a Reforested Brazilian Savannah for biodegradation of Esfenvarelate. Biodegradation, properties, analysis and performance; Nova Science Publishers: New York, 2016, pp. 161-200.
[44]
CLSI. Performance standards for antimicrobial disk suscepti-bility tests, CLSI document M02-A11; Clinical and Laboratory Standards Institute: Wayne, PA, 2012.
[45]
NCCLS; Method for antifungal disk diffusion susceptibility testing of yeasts NCCLS document MA44-A; (ISBN 1-56238-532-1). NCCLS: USA, 2004.
[46]
Abbas, H-A.S.; Al-Marhabi, A.R.; Eissa, S.I.; Ammar, Y.A. Molecular modeling studies and synthesis of novel quinoxaline derivatives with potential anticancer activity as inhibitors of c-Met kinase. Bioorg. Med. Chem., 2015, 23(20), 6560-6572.
[http://dx.doi.org/10.1016/j.bmc.2015.09.023] [PMID: 26420384]
[47]
Porter, J.; Lumb, S.; Franklin, R.J.; Gascon-Simorte, J.M.; Calmiano, M.; Riche, K.L.; Lallemand, B.; Keyaerts, J.; Edwards, H.; Maloney, A.; Delgado, J.; King, L.; Foley, A.; Lecomte, F.; Reuberson, J.; Meier, C.; Batchelor, M. Discovery of 4-azaindoles as novel inhibitors of c-Met kinase. Bioorg. Med. Chem. Lett., 2009, 19(10), 2780-2784.
[http://dx.doi.org/10.1016/j.bmcl.2009.03.110] [PMID: 19369077]
[48]
Nishii, H.; Chiba, T.; Morikami, K.; Fukami, T.A.; Sakamoto, H.; Ko, K.; Koyano, H. Discovery of 6-benzyloxyquinolines as c-Met selective kinase inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(4), 1405-1409.
[http://dx.doi.org/10.1016/j.bmcl.2009.12.109] [PMID: 20093027]
[49]
Ingle, R.; Marathe, R.; Magar, D.; Patel, H.M.; Surana, S.J. Sulphonamido-quinoxalines: Search for anticancer agent. Eur. J. Med. Chem., 2013, 65, 168-186.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.028] [PMID: 23708011]
[50]
Suffness, M.; Pezzuto, J.M. Assays for Bioactivity.Methods in Plant Biochemistry; K., H., Ed; Academic Press: London; , 1990, pp. 71-133.
[51]
Boik, J. Natural compounds in cancer therapy; Oregon Medical Press: Minnesota, USA, 2001.
[52]
O’Brien, J.; Wilson, I.; Orton, T.; Pognan, F. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur. J. Biochem., 2000, 267(17), 5421-5426.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01606.x] [PMID: 10951200]
[53]
Desplat, V.; Vincenzi, M.; Lucas, R.; Moreau, S.; Savrimoutou, S.; Pinaud, N.; Lesbordes, J.; Peyrilles, E.; Marchivie, M.; Routier, S.; Sonnet, P.; Rossi, F.; Ronga, L.; Guillon, J. Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines. Eur. J. Med. Chem., 2016, 113, 214-227.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.047] [PMID: 26945110]
[54]
Galal, S.A.; Khairat, S.H.M.; Ragab, F.A.F.; Abdelsamie, A.S.; Ali, M.M.; Soliman, S.M.; Mortier, J.; Wolber, G.; El Diwani, H.I. Design, synthesis and molecular docking study of novel quinoxalin-2(1H)-ones as anti-tumor active agents with inhibition of tyrosine kinase receptor and studying their cyclooxygenase-2 activity. Eur. J. Med. Chem., 2014, 86, 122-132.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.048] [PMID: 25147154]
[55]
Wu, P.; Su, Y.; Liu, X.; Yang, B.; He, Q.; Hu, Y. Discovery of novel 2-piperidinol-3-(arylsulfonyl)quinoxalines as phosphoinositide 3-kinase α (PI3Kα) inhibitors. Bioorg. Med. Chem., 2012, 20(9), 2837-2844.
[http://dx.doi.org/10.1016/j.bmc.2012.03.026] [PMID: 22480851]
[56]
Primas, N.; Suzanne, P.; Verhaeghe, P.; Hutter, S.; Kieffer, C.; Laget, M.; Cohen, A.; Broggi, J.; Lancelot, J-C.; Lesnard, A.; Dallemagne, P.; Rathelot, P.; Rault, S.; Vanelle, P.; Azas, N. Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-a]quinoxalines as new antiplasmodial agents. Eur. J. Med. Chem., 2014, 83, 26-35.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.014] [PMID: 24946216]
[57]
Zou, Y.; Qin, X.; Hao, X.; Zhang, W.; Yang, S.; Yang, Y.; Han, Z.; Ma, B.; Zhu, C. Phenolic 4-hydroxy and 3,5-dihydroxy derivatives of 3-phenoxyquinoxalin-2(1H)-one as potent aldose reductase inhibitors with antioxidant activity. Bioorg. Med. Chem. Lett., 2015, 25(18), 3924-3927.
[http://dx.doi.org/10.1016/j.bmcl.2015.07.048] [PMID: 26227780]
[58]
Manohara Reddy, S.A.; Mudgal, J.; Bansal, P.; Vasanthraju, S.G.; Srinivasan, K.K.; Rao, C.M.; Gopalan Kutty, N. Antioxidant, anti-inflammatory and anti-hyperglycaemic activities of heterocyclic homoprostanoid derivatives. Bioorg. Med. Chem., 2011, 19(1), 384-392.
[http://dx.doi.org/10.1016/j.bmc.2010.11.016] [PMID: 21146413]
[59]
Brahmeshwari, G.; Bhaskar, P.; Kumaraswamy, G. Synthesis and antibacterial activity of N-arylquinoxalin-2-amines bear-ing benzimidazole derivatives. J. Pharm. Sci. Res., 2015, 6, 752-756.
[60]
Keivanloo, A.; Bakherad, M.; Abbasi, F.; Besharati-Seidani, T.; Amin, A.H. Efficient synthesis of novel 1,2,3-triazole-linked quinoxaline scaffold via copper-catalyzed click reactions. RSC Adv., 2016, 6, 105433-105441.
[http://dx.doi.org/10.1039/C6RA22603E]
[61]
Rao, K.V.; Rock, C.P. Streptonigrin and related compounds. 6. Synthesis and activity of some quinoxaline analogues. J. Heterocycl. Chem., 1996, 33, 447-458.
[http://dx.doi.org/10.1002/jhet.5570330238]
[62]
Turnbull, P.C.B. Medical Microbiology; University of Texas Medical Branch at Galveston: Galveston, TX, 1996.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 6
Year: 2020
Published on: 01 October, 2020
Page: [900 - 910]
Pages: 11
DOI: 10.2174/1573407215666190318144105
Price: $65

Article Metrics

PDF: 21
HTML: 4
PRC: 1