Abstract
Since the beginning of the past century, quinoxaline 1,4-dioxide and phenazine 5,10-dioxide derivatives have been known to be potent bioactive compounds. Maybe the most relevant reported biological property has been their ability to act as bioreductive agents, selective cytotoxins against hypoxic cells; moreover, other significant activities have been identified, such as promotion-growth ability, antibacterial, antifungal, antiparasite, cytotoxic, as well as herbicide properties. Structure-activity relationship studies have been performed and important findings have been described. On the other hand, specific side effects for these compounds have been studied and identified being the most relevant mutagenic and clastogenic properties. These kinds of compounds have been also reported as components in the material sciences. This chapter includes old and more recent methods of synthesis of quinoxaline 1,4-dioxide and phenazine 5,10-dioxide derivatives, chemical and biological reactivity, biological properties and mode of action, structure-activity studies and other relevant chemical and biological properties.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Katritzky AR, Lagowski JN (1971) Chemistry of heterocyclic N-oxides. Academic Press, New York
Albini A, Pietra A (1991) Heterocyclic N-oxides. CRC Press, Boston
Dvoryantseva GG, Kaganskii MM, Musatova IS, Elina AS (1974) Khim Geterotsikl Soedin 1554
Pushkareva ZV, Varyukhina LV, Kokoshko Z (1956) Dokl Akad Nauk SSSR 108:1098
Aaron JJ, Maafi M, Párkányi C, Boniface C (1995) Spectrochim Acta 51A:603
Laursen JB, Nielsen J (2004) Chem Rev 104:1663
McIlwain H (1943) J Chem Soc 322
Haddadin MJ, Issidorides CH (1965) Tetrahedron Lett 36:3253
Douglass ML (1973) US Patent 3733323
Mahajanshetti CS, Balse MN (1978) Indian J Chem 16B:830
Bowie RA (1971) DE Patent 2127902
Kobayashi Y, Kumadaki I, Sato H, Sekine Y, Hara T (1974) Chem Pharm Bull 22:2097
Crommelynck F, Basso MT (1975) FR Patent 2265740
Sandtnerova R, Repas M, Bilik V (1987) CZ Patent 240379
Carmeli M, Rozen S (2006) J Org Chem 71:5761
Cooper MS, Heaney H, Newbold AJ, Sanderson WR (1990) Synlett 9:533
Haddadin MJ, Issidorides CH (1968) US Patent 3398141
Edwards ML, Bambury RE (1975) J Heterocycl Chem 12:835
Kluge AF, Maddox ML, Lewis GS (1980) J Org Chem 45:1909
Issidorides CH, Haddadin MJ (1982) US Patent 4343942
Monge A, Gil MJ, Pascual M (1983) Anal Real Acad Farm 49:199
Bowie RA, Jones G (1972) DE Patent 2136962
Usta JA, Haddadin MJ, Issidorides CH, Jarrar AA (1981) J Heterocycl Chem 18:655
Ludwig GW, Baumgartel H (1982) Chem Ber 115:2380
Monge A, Palop JA, Del Castillo JC, Calderó JM, Roca J, Romero G, Del Rio J, Lasheras B (1993) J Med Chem 36:2745
Monge A, Palop JA, Piñol A, Martínez-Crespo FJ, Narro S, González M, Sáinz Y, López de Ceráin A, Hamilton E, Barker AJ (1994) J Heterocycl Chem 31:1135
Monge A, Palop JA, López de Ceráin A, Senador V, Martínez-Crespo FJ, Sáinz Y, Narro S, García E, de Miguel C, González M, Hamilton E, Barker AJ, Clarke ED, Greenhow DT (1995) J Med Chem 38:1786
Monge A, Martínez-Crespo FJ, López de Ceráin A, Palop JA, Narro S, Senador V, Martín A, Sáinz Y, González M, Hamilton E, Barker AJ (1995) J Med Chem 38:4488
Barker AJ, Monge A, Hamilton E (1996) UK Patent 2297089
Ortega MA, Morancho MJ, Martínez-Crespo FJ, Sainz Y, Montoya ME, López de Ceráin A, Monge A (2000) Eur J Med Chem 35:21
Haroun M, Helissey P, Giorgi-Renault S (2001) Synth Commun 31:2329
Takabatake T, Miyazawa T, Kojo M, Hasegawa M (2000) Heterocycles 53:2151
Takabatake T, Miyazawa T, Takei A, Hasegawa M (2001) Igaku to Seibutsugaku 142:5
Takabatake T, Ito H, Takei A, Miyazawa T, Hasegawa M, Miyairi S (2003) Heterocycles 60:537
Sekimura N, Saito H, Miyairi S, Takabatake T (2005) Heterocycles 65:1589
Lima LM, Zarranz B, Marin A, Solano B, Vicente E, Pérez S, Aldana I, Monge A (2005) J Heterocycl Chem 42:1381
Lukasiewicz Z, Wrotek J (1976) PL Patent 86391
Monge A, Llamas A, Pascual MA (1977) An Quim 73:912
Monge A, Llamas A, Pascual MA (1977) An Quim 73:1208
Li J, Ji M, Hua W, Hu H (2001) Indian J Chem 40B:1230
Boulton AJ, Katritzky AR, Sewell MJ, Wallis B (1967) J Chem Soc B 914
Boulton AJ, Halls PJ, Katritzky AR (1970) J Chem Soc B 636
Cerecetto H, González M, Lavaggi ML, Porcal W (2005) J Braz Chem Soc 16:1290
Haddadin MJ, Issodorides CH (1976) Heterocycles 4:767
Edwards ML, Bambury RE, Kim HK (1976) J Heterocycl Chem 13:653
Issidorides CH, Haddadin MJ (1970) UK Patent 1215815
Boiani M, Boiani L, Denicola A, Torres de Ortiz S, Serna E, Vera de Bilbao N, Sanabria L, Yaluff G, Nakayama H, Rojas de Arias A, Vega C, Rolán M, Gómez-Barrio A, Cerecetto H, González M (2006) J Med Chem 49:3215
Mason JC, Tennant G (1970) J Chem Soc B 911
Seng F, Ley K (1972) Angew Chem Int Ed 11:1009
Suzuki H, Kawakami T (1997) Synthesis 8:855
Abushanab E (1970) DE Patent 1929541
Abushanab E (1970) J Org Chem 35:4279
Zarranz B, Jaso A, Aldana I, Monge A, Maurel S, Deharo E, Jullian V, Sauvain M (2005) Arzneim-Forsch 55:754
Cerecetto H, González M, Lavaggi ML, Azqueta A, López de Ceráin A, Monge A (2005) J Med Chem 48:21
Wang S, Miller W, Milton J, Vicker N, Stewart A, Charlton P, Mistry P, Hardick D, Denny WA (2002) Bioorg Med Chem Lett 12:415
Balicki R, Chmielowiec U (2000) Monats Chem 131:1105
Hahn WE, Lesiak J (1985) Pol J Chem 59:627
Balicki R, Cybulski M, Maciejewski G (2003) Synth Commun 33:4137
Balicki R (1990) Chem Ber 123:647
Kaczmarek L, Malinowski M, Balicki R (1988) Bull Soc Chim Belg 97:787
Malinoswaki M (1987) Synthesis 732
Novácek L, Nechvátal M (1988) Collect Czech Chem Commun 53:1302
Ahmed Y, Qureshi MI, Habib MS, Farooqi MA (1987) Bull Chem Soc Jpn 60:1145
Kotovskaya SK, Perova NM, Charushin VN, Chupakhin ON (1999) Mendeleev Commun 9:76
Kim HS, Hur JH (2004) J Korean Chem Soc 48:385
Amin KM, Ismail MMF, Noaman N, Soliman DH, Ammar YA (2006) Bioorg Med Chem 14:6917
Karayannis NM, Speca AX, Chasan DE, Pytlewski LL (1976) Coord Chem Rev 20:37
Matrosov EI, Starikova ZA, Khodak AA, Nifant'ev EE (2003) Zh Neorg Khim 48:2008
Torre MH, Gambino D, Araujo J, Cerecetto H, González M, Lavaggi ML, Azqueta A, López de Ceráin A, Monge A, Abram U, Costa-Filho AJ (2005) Eur J Med Chem 40:473
Noblía P, Vieites M, Torre MH, Costa-Filho AJ, Cerecetto H, González M, Lavaggi ML, Adachi Y, Sakurai H, Gambino D (2006) J Inorg Biochem 100:281
Martínez-Crespo FJ, Palop JA, Sáinz Y, Narro S, Senador V, González M, López de Ceráin A, Monge A, Hamilton E, Barker AJ (1996) J Heterocycl Chem 33:1671
Haddadin MJ, Issidorides CH (1967) Tetrahedron Lett 8:753
de Vries H, Bojarski J, Donker AA, Bakri A, Beyersbergen van Henegouwen GM (1990) Toxicol 63:85
Jarrar AA (1978) J Heterocycl Chem 15:177
Kawata H, Kikuchi K, Kokubun H (1983) J Photochem 21:343
Namba Y, Oda T, Watanabe T (1963) Bull Chem Soc Jpn 36:79
Cong Q, Lin S, Wang H (1989) Jiegou Huaxue 8:31
Jiang FQ, Hu YZ (2006) Acta Crystallogr E62:o649
Greer ML, Duncan JR, Duff JL, Blackstock SC (1997) Tetrahedron Lett 38:7665
Kraessig R, Bergmann D, Fliegen N, Kummer F, Seiffert W, Zimmermann H (1970) Berichte Bunsen-Ges 74:617
Andreev VP, Ryzhakov AV (1993) Khim Geterotsikl Soedin 1662
Limbach HH, Seiffert W, Ohmes E, Zimmermann H (1970) Berichte Bunsen-Ges 74:966
Stefaniak L (1976) Spectrochim Acta 32A:345
Guenther H, Gronenborn A (1978) Heterocycles 11:337
Panasyuk PM, Melnikova SF, Tselinskii IV (2005) Chem Heterocycl Comp 41:909
Brodskii AE, Gordienko LL, Degtyarev LS (1968) Electrochim Acta 13:1095
Kubota T, Nishikida K, Miyazaki H, Iwatani K, Oishi Y (1968) J Am Chem Soc 90:5080
Barqawi KR, Atfah MA (1987) Electrochim Acta 32:597
Ames JR, Houghtaling MA, Terrian DL (1992) Electrochim Acta 37:1433
Stüewe A, Weber-Schäefer M, Baumgäertel H (1972) Tetrahedron Lett 13:427
Stüewe A, Weber-Schäefer M, Baumgäertel H (1974) Berichte Bunsen-Ges 78:309
Koldasheva EM, Strelets VV, Tse YK, Geletii YV, Shestakov AF (1996) Izvestiya Akademii Nauk, Seriya Khimicheskaya 1992
Nishikida K, Kubota T, Miyazaki H, Sakata S (1972) J Mag Reson 7:260
Kulakovskaya SI, Kulikov AV, Berdnikov VM, Ioffe NT, Shestakov AF (2002) Electrochim Acta 47:4245
Stuewe A, Baumgaertel H (1974) Berichte Bunsen-Ges 78:320
Koldasheva EM, Shestakov AF, Geletii YV, Shilov AE (1992) Izvestiya Akademi Nauk, Seriya Khimicheskaya 845
Razskazovskiy Y, Close DM (2006) Res Chem Intermed 32:625
Acree WE, Powell JR, Tucker SA, Ribeiro da Silva MDMC, Matos MAR, Goncalves JM, Santos LMNBF, Morais VMF, Pilcher G (1997) J Org Chem 62:3722
Ribeiro da Silva MDMC, Gomes JRB, Gonçalves JM, Sousa EA, Pandey S, Acree WE (2004) Org Biomol Chem 2:2507
Ribeiro da Silva MDMC, Gomes JRB, Goncalves JM, Sousa EA, Pandey S, Acree WE (2004) J Org Chem 69:2785
Gomes JRB, Sousa EA, Gonçalves JM, Monte MJS, Gomes P, Pandey S, Acree WE, Ribeiro da Silva MDMC (2005) J Phys Chem B 109:16188
Gomes JRB, Sousa EA, Gomes P, Vale N, Gonçalves JM, Pandey S, Acree WE, Ribeiro da Silva MDMC (2007) J Phys Chem B 111:2075
Gomes JRB, Ribeiro da Silva MDMC, Ribeiro da Silva MAV (2006) Chem Phys Lett 429:18
Novacek L, Polasek L (1982) Biol Chem Zivocisne Vyroby – Vet 18:17
Oda M, Sekizawa Y, Watanabe T (1966) Appl Environ Microbiol 14:365
McIlwain H (1943) Biochem J 37:265
Carta A, Corona P, Loriga M (2005) Curr Med Chem 12:2259
Elina AS, Musatova IS, Padejskaya EN, Pershin GN (1993) RU Patent 677320
Ono M, Chen YSE, Marks DF (1997) JP Patent 09100231
Wu H (2005) CN Patent 1687038
Zhao R, Wang Y, Xue F, Xu Z, Li J, Li J, Yan X, Du X, Miao X (2006) CN Patent 1785979
Takahata T, Sekimura N, Sumiyoshi Y (2006) JP Patent 2006241111
Council Directive. OJ No L160/34, 20.6.1987:1–2
Suter W, Rosselet A, Knuesel F (1978) Antimicrob Agents Chemother 13:770
Fadeeva NI, Padeiskaya EN, Degtyareva IN, Pershin GN (1978) Farmakologiya i Toksikologiya 41:613
Usai D, Sanna P, Sechi LA, Carta A, Paglietti G, Zanetti S (2004) L'Igiene Moderna 121:289
Carta A, Paglietti G, Rahabar Nikookar ME, Sanna P, Sechi L, Zanetti S (2002) Eur J Med Chem 37:355
Carta A, Loriga M, Paglietti G, Mattana A, Fiori PL, Mollicotti P, Sechi L, Zanetti S (2004) Eur J Med Chem 39:195
OMS. WHO annual report on global TB control summary (2003) Weekly Epidemiol Rec 78:121
Sainz Y, Montoya ME, Martínez-Crespo FJ, Ortega MA, López de Ceráin A, Monge A (1999) Arzneim-Forsch 49:55
Ortega MA, Sáinz Y, Montoya ME, López de Ceráin A, Monge A (1999) Pharmazie 54:24
Ortega MA, Sáinz Y, Montoya ME, Jaso A, Zarranz B, Aldana I, Monge A (2002) Arzneim-Forsch 52:113
Montoya ME, Sáinz Y, Ortega MA, López de Ceráin A, Monge A (1998) Farmaco 53:570
Ortega MA, Montoya ME, Jaso A, Zarranz B, Tirapu I, Aldana I, Monge A (2001) Pharmazie 56:205
Zarranz B, Jaso A, Aldana I, Monge A (2003) Bioorg Med Chem 11:2149
Jaso A, Zarranz B, Aldana I, Monge A (2003) Eur J Med Chem 38:791
Jaso A, Zarranz B, Aldana I, Monge A (2005) J Med Chem 48:2019
Zanetti S, Sechi L, Molicotti P, Cannas S, Bua A, Deriu A, Carta A, Paglietti G (2005) Int J Antimicrob Agents 25:179
WHO Thirteenth Program Report: UNDP/World Bank/World Health Organization program for research and training in tropical diseases (1997) Geneva
Aldana I, Ortega MA, Jaso A, Zarranz B, Oporto P, Giménez A, Monge A (2003) Pharmazie 58:68
Zarranz B, Jaso A, Lima LM, Aldana I, Monge A, Maurel S, Sauvain M (2006) Braz J Pharm Sci 42:357
Cerecetto H, Di Maio R, González M, Risso M, Saenz P, Seoane G, Denicola A, Peluffo G, Quijano C, Olea-Azar C (1999) J Med Chem 42:1941
Aguirre G, Cerecetto H, Di Maio R, González M, Montoya ME, Jaso A, Zarranz B, Ortega MA, Aldana I, Monge A (2004) Bioorg Med Chem Lett 14:3835
Urquiola C, Vieites M, Aguirre G, Marín A, Solano B, Arrambide G, Noblía P, Lavaggi ML, Torre MH, González M, Monge A, Gambino D, Cerecetto H (2006) Bioorg Med Chem 14:5503
Overgaard J (1989) Int J Radiat Biol 56:801
Lin AJ, Cosby LA, Shansky CW, Sartorelli AC (1972) J Med Chem 15:1247
Cerecetto H, González M (2001) Mini-Rev Med Chem 1:219
Daniels JS, Gates KS (1996) J Am Chem Soc 118:3380
Zamalloa E, Aldana I, Bachiller CM, Monge A (1997) Arzneim-Forsch 47:873
Zamalloa E, Dios-Viéitez C, González-Peñas E, Monge A, Aldana I (1997) Arzneim-Forsch 47:1044
Vieites M, Noblía P, Torre MH, Cerecetto H, González M, Lavaggi ML, Da Costa Filho AJ, López de Ceráin A, Monge A, Parajón-Costa B, Gambino D (2006) J Inorg Biochem 100:1358
Lin PS, Ho KC (1998) J Nucl Med 39:677
Zhang W, Wu Y, Lu W, Li W, Sun X, Shen X, Li X, Tang L (1995) Zhongguo Yaowu Huaxue Zazhi 5:242
Gali-Muhtasib HU, Haddadin MJ, Rahal DN, Younes IH (2001) Oncol Rep 8:679
Cerecetto H, González M, Lavaggi ML, Aravena MA, Rigol C, Olea-Azar C, Azqueta A, López de Ceráin A, Monge A, Bruno AM (2006) Med Chem 2:511
Ganley B, Chowdhury G, Bhansali J, Daniels JS, Gates KS (2001) Bioorg Med Chem 9:2395
Chowdhury G, Kotandeniya D, Daniels JS, Barnes CL, Gates KS (2004) Chem Res Toxicol 17:1399
Diab-Assef M, Haddadin MJ, Yared P, Assaad C, Gali-Muhtasib HU (2002) Mol Carcinog 33:198
Gali-Muhtasib HU, Diab-Assaf M, Haddadin MJ (2005) Cancer Chem Pharmacol 55:369
Azqueta A, Pachón G, Cascante M, Creppy EE, López de Ceráin A (2005) Mutagenesis 20:165
Azqueta A, Pachón G, Cascante M, Creppy EE, López de Ceráin A (2007) Chem-Biol Interact 168:95
Zarranz B, Jaso A, Aldana I, Monge A (2004) Bioorg Med Chem 12:3711
Gali-Muhtasib H, Sidani M, Geara F, Mona AD, Al-Hmaira J, Haddadin MJ, Zaatari G (2004) Int J Oncol 24:1121
Nagai K, Hecht SM (1991) J Biol Chem 266:23994
Helissey P, Giorgi-Renault S, Colson P, Houssier C, Bailly C (2000) Bioconjugate Chem 11:219
Cerecetto H, Dias E, Di Maio R, González M, Pacce S, Saenz P, Seoane G, Suescun L, Mombrú A, Fernández G, Lema M, Villalba J (2000) J Agric Food Chem 48:2995
Jingzhong M, Chaonan H, Shengwei Z, Jianhong L, Hong J (2005) Xiandai Huagong 25:34
Kang IY, Kim SY, Kim HS, Huh K (1990) Yakhak Hoechi 34:112
Leach SC, Weaver RD, Kinoshita KL, William W (1981) J Electroanal Chem Interf Electrochem 129:213
Ryan MD, Scamehorn RG, Kovacic P (1985) J Pharm Sci 74:492
Crawford PW, Scamehorn RG, Hollstein U, Ryan MD, Kovacic P (1986) Chem-Biol Interact 60:67
Schoenfelder D, Stumm G, Bohle M, Niclas J (1988) Pharmazie 43:837
Gomes JRB, Ribeiro da Silva MDMC, Ribeiro da Silva MAV (2006) Chem Phys Lett 429:18
Hashimoto T, Negishi T, Namba T, Hayakawa S, Hayatsu H (1979) Chem Pharm Bull 27:1954
Voogd CE, Van der Stel JJ, Jacobs JJJAA (1980) Mut Res 78:233
Negishi T, Tanaka K, Hayatsu H (1980) Chem Pharm Bull 28:1347
Beutin L, Preller E, Kowalski B (1981) Antimicrob Agents Chemother 20:336
Cihak R, Srb V (1983) Mut Res 116:129
Cihak R, Vontorkova M (1983) Mut Res 117:311
Yoshimura H (2002) Toxicol Lett 129:115
Hao L, Chen Q, Xiao X (2006) Mut Res Fund Mol Mech Mut 599:21
Fuchs T, Gates KS, Hwang JT, Greenberg MM (1999) Chem Res Toxicol 12:1190
Inbaraj JJ, Motten AG, Chignell CF (2003) Chem Res Toxicol 16:164
Crosby J, Milner JA (1979) UK Patent 2010850
Graves DF, Engels HW (1988) EU Patent 289752
Yamamoto T (1997) Int Appl Patent 9715607
Morioka Y, Sato M, Iwasa S, Iriyama J, Nakahara K, Suguro M (2003) JP Patent 2003115297
Iriyama J, Morioka Y, Iwasa S, Nakahara K, Sato M, Suguro M (2003) JP Patent 2003178801
Morioka Y, Iwasa S, Iriyama J, Yamamoto H, Nakahara K, Suguro M, Sato M (2004) JP Patent 2004192829
Author information
Authors and Affiliations
Corresponding author
Editor information
Rights and permissions
Copyright information
© 2007 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
González, M., Cerecetto, H., Monge, A. (2007). Quinoxaline 1,4-Dioxide and Phenazine 5,10-Dioxide. Chemistry and Biology. In: Khan, M.T.H. (eds) Bioactive Heterocycles V. Topics in Heterocyclic Chemistry, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7081_2007_066
Download citation
DOI: https://doi.org/10.1007/7081_2007_066
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-73405-5
Online ISBN: 978-3-540-73406-2
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)