A REVIEW ON BIOLOGICAL STUDIES OF QUINOXALINE …

11
Ali et al. World Journal of Pharmacy and Pharmaceutical Sciences
A REVIEW ON BIOLOGICAL STUDIES OF QUINOXALINE
DERIVATIVES
1 , Muhammad Umer
1 , Sajjad Ahmad
Department of Chemistry, The University of Lahore, Sargodha Campus, Pakistan.
2 Department of Chemistry, UET Lahore, Pakistan.
ABSTRACT
Quinoxaline moieties are nitrogen containing heterocyclic derivatives
which have broad spectrum biological and pharmaceutical
applications. The quinoxaline derivatives are used for the cure of vast
range of various diseases. Modifications in structure of quinoxaline
substrates have provided applications in various fields and developed
remarkable efficacy against diseases with lesser side effects. In this
account, glimpses of such quinoxaline derivatives have been presented
known for their activity as antiprotozoal, anticancer, antimalarial,
antimicrobial antiviral, anti-inflammatory, antidiabetic, anti-tubercular,
anti-nociceptive, anthelmintic and as a kinase inhibitor.
KEYWORDS: Bioactive quinoxaline, anticancer, antimicrobial, antineoplastic, anti-
inflammatory.
INTRODUCTION
Organic compounds which are formed by replacing carbon atoms of ring with one or more N,
O or S elements are called as heterocyclic organic compounds. Quinoxaline moiety and its
derivatives are belonged to class of nitrogen containing heterocyclic compounds with broad
range of biological activities and pharmacological applications. [1]
Benzopyrine and
diazanaphthalene are its other names. Quinoxaline ring atoms are numbered as below in
Figure 1. The number of resonance structures of quinoxaline increases by the fusion of one or
more benzene rings to quinoxaline and phenazine rings and the dipole moment of quinoxaline
is zero. [2]
DOI: 10.20959/wjpps20172-8533
SJIF Impact Factor 6.647
Volume 6, Issue 02, 11-30 Review Article ISSN 2278 – 4357
www.wjpps.com Vol 6, Issue 2, 2017.
12
Quinoazoline, cinnolenes and phthalazines are isomeric with quinoxline. Quinoxaline is
formed by the fusion of diazine with benzene ring. Some of heterocyclic system are given
below. [3]
Figure 2: Hetrocyclic compounds
Quinoxaline derivatives which have a wide variety of potential applications in biological,
medicinal and pharmacological fields. [4]
Quinoxaline derivatives act as antiprotozoal,
antiviral, anti-inflammatory, and antibacterial and as a kinase inhibitor. [5]
Quinoxaline have
receptor. Quinoxaline derivatives showed anticancer, antimalarial, antimicrobial, anti-
nociceptive, antiepileptic, antidiabetic, anti-tubercular and anthelmintic characteristics. [6]
Figure 3: Biological activities of quinoxaline derivatives.
13
The present study shows advancement in synthesis and biological diversities of quinoxaline
derivatives to develop new pathways for therapeutic targets, drug design and future drug
discovery.
Abid & Azam reported substituted indophenazines quinoxaline derivative 1 as anti-amoebic
and psychotropic agent as well as anti-inflammatory. The derivative 1 was formed by the
refluxing of 1-N-thio-carboxamide-3-phenyl-2-pyrazolines with 1,2-dichloroquinoxaline. [7]
Wagle et al screened 3-Methyl-7-substituted-1{[5-(aryl)-1,3,4-oxadiazoles-2-yl]-methyl}-
quinoxaline-2(1H)-ones as best anti-inflammatory compound. Non-steroidal anti-
inflammatory drugs (NASID) were used for inflammation, arthritis, margarine, fever or for
acute and chronic pains. [8]
N
Thioquinox 3 (a quinoxaline derivative) demonstrated a potential antifungal activities as
reported by Laddah & Bhatanagar. [9]
N
N
S
14
reaction between the phenazine derivative and the indenoquinoxaline by Soliman. [10]
N
N
O
O
R1
HN2
Chloro quinoxaline sulphonamide 5 is used as anti-neoplastic. Quinoxaline derivatives have
inhibitory activity against human cancer cells lines. The platelet-derived growth factor
(PDGF) receptor kinase is inhibited selectively by quinoxaline derivatives reported by Gao et
al. [11]
Quinoxaline carboxamide derivative showed 5-HT3 (setrons) receptor antagonistic is class of
drugs which treated nausea and vomiting due to induced cancer. The condensation of
Mannich bases like p-amino phenol reacted with 3-chloro-2-quinoxaloylchloride to afford
carboxamide quinoxaline derivatives by Mahesh et al. [12]
N
N
Cl
O
CH2R
OH
R1
6
15
Yoo et al synthesized 7, 8-Bis(bromomethyl)benzo[g]quinoline-5,10-dione 7 which exhibited
excellent cytotoxic effect against leiomyosarcoma, liposarcoma, fibroblastic,
rhabdomyosarc-omas, synovial sarcomas, angiosarcoma and kaposi's sarcoma etc. [13]
N
Br
Br
O
O
7
Figure 10: 7,8-Bis(bromomethyl)benzo[g]quinoline-5,10-dione 7
Deleuze et al reported imidazo[1,2-a]quinoxaline analogues 8 and 9 were synthesized by
condensation of 2-imidazole carboxylic acid, followed by a coupling with ortho-
fluoroaniline. These quinoxaline derivatives showed prominent antitumor activities against
human amelanotic melanoma cell line (A 375 cells). These analogues were used in cytokine
research in outside of living organism or in vitro but not in vivo. [14]
N
N
Figure 12: Antitumor Imidazo[1,2-a]quinoxaline analogues 9
Monoamine oxidases (MAO) belonged to a family of enzymes that catalyze the oxidation of
monoamines and acted as inhibitors chemicals which inhibited the activity of the monoamine
oxidase enzyme family. Some novel monoamine oxidase A inhibitors (MAO) such as 3-
benzyl-2-substituted quinoxalines derivatives treated Parkinson’s disease, depression and
anxiety disorders was prepared by Seham et al. [15]
16
N
N
N
R1
R2
R3
H
R4
10
1,2,3-Trisubstituted-1,4-dihydrobenzoquinoxaline-5,10-diones derivative 11 showed
excellent antibacterial activity in biological cultures in slants or petri dishes was determined
by Vishnu et al. [16]
N
N
O
O
OH
H
11
OH
C
Kleim et al prepared quinoxaline derivatives such as 6-chloro-3,3-dimethyl-
4(isopropenyloxy-carbonyl)-3,4-dihydroquinolin-2-(1H)-thione and (S)-4-
isopropoxycarbonyl-6-methoxy-3-methylthiomethyl-3,4-dihydroquinoxaline-2(1H)-thione
(HBY 097) 12 exhibited anti HIV activity against HIV reverse transcriptase enzyme
inhibitor. [17]
The quinoxaline derivatives N-(4-fluorophenyl)-2-(3-oxo-3,4-dihydroquinoxalin-2-yl)
hydrazine carbothioamide 13 were used in the treatment of high sugar level (anti-diabetic)
called as mild hypoglycemic agent by Reddy et al. [18]
17
N
Figure 16: Quinoxaline derivative as mild hypoglycemic agent 13
Li afforded quinoxaline derivative based Brimonidin (Alphagan) 14 drug is called 5-bromo-
N-(2H-imidazol-2-yl)quinoxalin-6-amine and used to treat the intraocular pressure and the
eyes diseases especially glaucoma in which symptoms appeared like increased pressure
within the eyeball that causing gradual loss of sight. [19]
Figure 17: Quinoxaline Alphgan drug derivative 14
6-Chloro-7-((4-hydroxyphenyl)amino)-2,3-di(pyridin-2-yl)quinoxaline-5,8-dione derivative
15 exhibited excellent and highest anti-proliferative activity was screened by Chung et al. [20]
N
N
O
O
Cl
Figure 18: Quinoxaline derivative 15 an anti-proliferative agent
Selvam et al synthesized diphenyl quinoxaline (DPQ) 16 which showed inhibitory activity in
vitro against the aids virus HIV-1 (111B) replication in human metallothionein 4 cells (MT-4
cells). [21]
18
N,6,7-triphenylquinoxaline-2-sulfonamide 18 and N-((6,7-diphenylquinoxalin-2-
properties were prepared by Rahul & Rajendra. [22]
N
NPh
Ph
N
NPh
Ph
S
N
NPh
Ph
Figure 22: Quinoxaline derivative 19 showing anti-inflammatory activity
The amino acids in the peptide chains of triostin-A 20 and quinomycin 21 are: D-Ser (D-
serine), Ala (Alanine), MeCys (N-Methyl-L-cysteine), MeVal (N-Methyl-L-valine) reported
by Gauvreau & Waring. [23]
19
N
N
O
Quinoxaline derivatives 6,7-dimethyl-2-phenylquinoxaline (AG 1295) 22 & 2-
phenylbenzo[g]quinoxaline (AG 1385) 23 showed the specific blocking EGFR kinase and
ATP competitive inhibitory properties determined by Kovalenko et al. [24]
N
N
22
Figure 25: EGFR Tyrosine Kinase inhibitors of quinoxaline derivative 22
N
N
23
Figure 26: EGFR Tyrosine Kinase inhibitors of quinoxaline derivative 23
Eslam et al synthesized following quinoxaline-2,3-diones derivatives 6-isocyano-7-
nitroquinoxaline-2,3(1H,4H)-dione (CNQX) 24, 6,7-dinitroquinoxaline-2,3(1H,4H)-dione
which demonstrated excellent anticonvulsant activities. [25]
H N
N H
20
H N
N H
Ahoya et al reported 2-Methylquinoline-3(4H)-thione 27 showed less antibacterial activities
than 4-ethyl-2-methylquinoline-3(4H)-thione 28 as compared to the standard references of
clotrimazole and tetracycline. [26]
N CH3
Figure 31: Antibacterial quinoxaline derivatives 28
Umarani Natarajan et al reported the tetrazolo quinoxaline derivatives 29d and 29f were
showed high antimicrobial activities while 29g and 29h exhibited optimum potent
antimicrobial properties. The compound 29j was moderately active while compound 29i was
showed mild antimicrobial activity against the tested strains. The derivative 29i was optimum
potent and showed remarkable anti-inflammatory activity. The derivative 29j was exhibited
closely in anti-inflammatory activities to compound 29i. The moderate anti-inflammatory
21
activity was showed by compounds 29a-h. In short the derivatives 29i and 29j exhibited
optimum anti-inflammatory activity but showed minimum antimicrobial characteristics and
activity. The rest of derivatives in the synthesized series showed moderate anti-inflammatory
but remarkable high antimicrobial activities. [27]
29a 2-OH- (C6H4),29b 3-OH- (C6H4), 29c 4-OH- (C6H4), 29d 2-NO2 - (C6H4)
29e 3-NO2 - (C6H4), 29f 4-NO2
- (C6H4), 29g 2-Cl- (C6 H4), 29h 4-Cl- (C6 H4) 29i 2-N (CH3)2C6H4, 29j 3, 4, 5- (OCH3)3C6H2
N
R29
Figure 32: Synthesis of schiff's bases of tetrazolo[1,5-a] quinoxalines 29
The quinoxaline derivatives 35 a-d and 38 exhibited anticonvulsant activity similar to
compounds 30-34. The compound 37 was the best anticonvulsant agent. The compound 36b
was equipotent in anxiolytic effect with that of diazepam. The derivatives 36d and 37 were
induced more anxiolytic effect than diazepam. Therefore these derivatives were considered
most potent and active in anxiolytic effect. The functional groups of compounds 36, 36b, 38
and 39 were lack ability to induce anxiolytic effect while all these derivatives showed
sedative effects reported by Olayiwola et al. [28]
H N
N H
22
N
receptor antagonists
H N
N H
R O
O
36
98a R=H, 98b R=Cl, 98c R=CH3, 98d R= NO2
Figure 34: Substituted Quinoxaline-2, 3-diones derivatives
N H
23
N
N
Figure 37: Substituted Quinoxaline-2, 3-diones derivatives
Ali et al afforded the quinoxalin-2-ones 40 and quinoxaline-2,3-diones 41 which
demonstrated antimicrobial activity. [29]
N
Figure 38: Substituted Quinoxaline-2-dione & Quinoxaline-2, 3-diones derivatives
Osama, S. M. screened quinoxaline derivative 42 and 43 which were highly active against
Gram positive bacteria and exhibited excellent inhibitory growth. Antifungal activities
showed by 42 and 44 derivatives against the tested strains of fungi. It was concluded that the
derivatives 42, 43 and 44 exhibited remarkable antimicrobial activities. [31]
24
N
Figure 39: Synthesis of pyridinyl and isoxazolyl quinoxaline derivatives
The quinoxaline derivatives 46, 47a, 47c, 47d, 47e, 49a and 49c were showed excellent
antibacterial activity against both Gram positive and Gram negative bacteria. Antibacterial
activity against E. coli. were exhibited by 47c, 47d, 49a, 49c and 49e. The antibacterial
activity was not showed by compound 49d against Escherichia coli and Pseudomonas
aeruginosa. The quinoxaline derivatives 49b and 49c were not exhibited antimicrobial
characteristics against Pseudomonas aeruginosa. As we introduced aromatic ring and –CH3
group in the compounds, the lipophilicity of the compounds were increased. High
antibacterial activity of these compounds 46, 47a, 47c, 47d, 47e and 49c were due to
increase in lipophilicity which resulted in permeability through the microbial cell wall. The
derivative 49d was showed best antimicrobial activities due to presence of –COOH and was
considered as analogue to famous antimicrobial agent benzoic acid.
The quinoxaline derivatives 46, 48, and 49a acted as moderate antifungal agent against both
A. niger and C. albicans strains. The quinoxaline compounds 47b, 47c, 47d and 47e exhibited
no activity against C. albicans while showed moderate antifungal activity against A. niger.
25
Compounds of quinoxaline 47a, 47b, 47c, 49d and 49e showed no activity against A.
niger. [32]
N-((4-(2-methylquinoxalin-3-yloxy)phenyl)methylene)-4-substituted benzenamine
R= H, Cl, CH3, 4-COOH, 2- CH2 , 6- CH3 Compounds 47(a-e)
N
N
O
CH
47
4-(2-methylquinoxalin-3-yloxy)-N-substituted benzylidene benzenamine
R= 4-OH, 2-NO2, 4-N(CH3)2, 2-OH, 3-OCH, 2-OCH3, 3-OCH3, 4-OCH3 Compounds 49(a-e)
Chih-Hua reported that 11-(3-(dimethylamino) propoxyimino)-N-(3-(dimethylamino)
propyl)-11H-indeno [1,2-b]quinoxaline-6-carboxamide demonstrated inhibitory activities
topoisomerase-1 and topoisomerase-2 with reference to control compound. Zebrafish
Xenograft method confirmed the anti-tumor activities of compound 50. [33]
26
N
which exhibited anti-proliferative activities against both human non- small cell lung
carcinoma and glioblastoma cell lines. [34]
N
The nitrogen containing heterocyclic quinoxaline core can easily be synthesized and modified
into different derivatives which have potential biological, pharmacological and medicinal
applications. The quinoxaline compounds are pharmacophore and have diverse applications
in biological, pharmacological and organic material chemistry fields. Quinoxaline is
important moiety which is biologically active and exhibit excellent and remarkable clinical
and therapeutic properties. The plethora of research mentioned in this review article is helpful
to develop such strategies and methodologies to synthesize new generation of quinoxaline
skeleton based therapeutic agents, drugs and analogues which have optimum potent efficacy,
no cytotoxicity and greater bio absorption.
ACKNOWLEGMENT
Author is much acknowledged to Dr. Ameer Fawad Zhaoor Assistant Professor, Institute of
chemistry, G. C University Faisalabad for providing facilities necessary for the publication of
this article.
27
REFERENCES
1. Katritzky AR. In Comprehensive Heterocyclic Chemistry: the structure, reactions,
synthesis, and uses of heterocyclic compounds. Rees, C.W Eds. Pergamon Press: Oxford
U.K: 1984; pp: 157–97.
2. Noorulla S, Sreenivasulu N. Antibacterial activity of novel substituted quinoxaline
heterocycles with isoniazide. International Journal of Research in Pharmaceutical and
Biomedical Sciences, 2011; 2: 1100-6.
3. Ganapaty, Ramalingam P, Rao B. Sar Study: Impact of hydrazide hydrazones and
sulfonamide side chain on in vitro antimicrobial activity of quinoxaline. International
Journal of Pharmacology and Biological Sciences, 2011; 2: 13-18.
4. Loriga M, Moro P, Sanna P, Paglietti G, Zanetti S. 2-[Anilino]-3-(carboxyl)-6 (7)-
substituted quinoxalines as non-classical antifoate agents. Synthesis and evaluation of
anti-cancer, anti-HIV and antifungal activity. ILFARMACO, 1997; 52: 531-37.
5. Seitz LE, Suling WJ, Reynolds RC. Synthesis and antimycobacterial activity of pyrazine
and quinoxaline derivatives. Journal of Medicinal Chemistry, 2002; 45: 5604-6.
6. Bahekar RH, Jain MR, Gupta AA, Goel A, Jadav PA, Patel DN, Prajapati VM, Patel PR.
Synthesis and antidiabetic activity of 3, 6, 7-trisubstituted-2-(1H-imidazol-2-ylsulfanyl)
quinoxalines and quinoxalin-2-yl isothioureas. Archiv Der Pharmazie, 2007; 340: 359-66.
7. Abid M, Azam A. Synthesis, characterization and antiamoebic activity of 1-(thiazolo[4,5-
b]quinoxaline-2-yl)-3-phenyl-2-pyrazoline derivatives. Bioorganic & Medicinal
Chemistry Letters, 2006; 16: 2812-16.
8. Wagle S, Adhikari VA, Kumari SN. Synthesis of some new 2-(3-methyl-7- substituted-2-
oxoquinoxalinyl)-5-(aryl)-1,3,4-oxadiazoles as potential non-steroidal anti-inflammatory
and analgesic agents. Indian Journal of Chemistry, 2008; 47B: 439-48.
9. Laddah SS, Bhatnagar SP. Novel Fused quinazolinones. Further studies on the
anticonvulsant activity of 1,2,9,11 tetrasubstituted-7H-thieno[2’,3’:4,5]pyrimido[6,1-b]-
quinazolin-7-one and1,3,10,12-tetrasubstituted-8H-pyrido[2’,3’:4,5]pyrimido[6,1-
b]quinazolin-8-one. Bioorganic and Medicinal Chemistry, 2009; 17: 6796-6802.
10. Soliman HS. Synthesis, characterization, anti-bacterial and anti-fungal activities of new
quinoxaline-1,4-di-N-Oxide derivatives. International Journal of Organic Chemistry,
2013; 3: 65-72.
11. Gao H, Yamasaki EF, Chan KK, Shen LL, Snapka RM. Chloroquinoxaline sulfonamide
(NSC 339004) is a topoisomerase IIα/β poison. Cancer Research Journal, 2000; 60: 5937-
40.
28
12. Mahesh R, Perumal RV, Pandi PV. Pharmacophore based synthesis of 3-
chloroquinoxaline-2-carboxamides as serotonin 3 (5-HT3) receptor antagonist. Biological
and Pharmaceutical Bulletin, 2004; 27: 1403-5.
13. Yoo HW, Suh ME, Park SW. Synthesis and cytoxicity of 2-methyl-4,9-dihydro-1-
substituted-1H-imidazo[4,5-g]quinoxaline-4,9-diones and 2,3-disubstituted-5,10-
pyrazino[2,g]quinoxalinediones. Journal of Medicinal Chemistry, 1998; 41: 4716-22.
14. Deleuze MC, Moarbess G, Khier S, Gayraud PS, Bressolle F, Pinguet F, Bonnet PA. New
imidazole[1,2-a]quinoxaline derivatives: synthesis and in vitro activity against human
melanoma. European Journal of Medicinal Chemistry, 2009; 44: 3406-11.
15. Seham YH, Sherine NK, Adnan AB, Adel A. Synthesis of 3-benzyl-2-substituted
quinoxalines as novel monoamine oxidase A inhibitors. Bioorganic & Medicinal
Chemistry Letters, 2006; 16: 1753–56.
16. Vishnu KT, Dharmendra BY, Hardesh KM, Ashok KC, Praveen KS. Design, synthesis
and biological evaluation of 1,2,3-trisubstituted-1,4-dihydrobenzo[g]quinoxaline-5,10-
diones and related compounds as antifungal and antibacterial agents. Bioorganic and
Medicinal Chemistry, 2006; 14: 6120-26.
17. Kleim J, Bender R, Billhard U, Meichsner C, Riess G, Rosner M, Winkler I, Paessens A.
Activity of a novel quinoxaline derivative against human immunodeficiency virus type1
reverse transcriptase and viral replication. Antimicrobial Agents and Chemotherapy,
1993; 37: 1659-64.
18. Reddy S, Marwah CV, Marwah AK, Rao GS. Synthesis and biological activity of some
new N-arylcarbamoyl and arylthiocarbamoyl hydrazinoquinoxalin-2-ones. .Indian Journal
of Chemistry, 1989; 8B: 885–91.
19. Li JJ. Synthesis of novel 3-substituted pyrrolo[2,3-b]quinoxalines via an intermolecular
Heck Reaction on an aminoquinoxaline scaffold. The Journal of Organic Chemistry,
1999; 64: 8425-27.
20. Chung JH, Jung JO, Chae JM, HongYuS, Chung HK, Lee KS, Chung KR. Synthesis and
biological evaluation of quinoxaline-5, 8-diones that inhibit vascular smooth muscle cell
proliferation. Bioorganic & Medicinal Chemistry Letters, 2005; 15: 3380-84.
21. Selvam P, Chandramohan M, Christophe P, De-Clercq E. Studies on antiviral activity of
2,3–diphenylquinoxalin. International Journal of Pharmacy & Industrial Research, 2011;
01: 138-40.
29
22. Rahul GI, Rajendra PM. Sulfonamido Quinoxalines - search for anti-inflammatory
agents. International Journal of Pharmaceutical Research & Allied Sciences, 2012; 1: 46-
51.
23. Gauvreau D, Waring JM. Directed biosynthesis of novel derivatives of echinomycin.
Canadian Journal of Microbiology, 1984; 30: 730-38.
24. Kovalenko M, Gazit A, Böhmer A, Rorsman C, Rönnstrand L, Heldin CH, Waltenberger
J, Böhmer FD, Levitzki A. Selective platelet-derived growth factor receptor kinase
blockers reverse sis-transformation. Cancer Research Journal, 1994; 54: 6106-14.
25. Eslam E, Adel G, Ahmed E, Kamal E, Helmy S. Synthesis and biological evaluation of
some quinoxaline-2-one derivatives as novel anticonvulsant agents. Chemical Science
Review and Letters, 2014; 3: 1375-87.
26. Ahoya AC, Daouda B, Bouhfid R, Hançali A, Bousmina M, Zerzouf A, Essassi E.
Synthesis and antibacterial activity of new spiro[thiadiazolinequinoxaline] derivative.
Arkivoc Journal, 2011; 2: 217-26.
27. Umarani N, Ilango K, Narendra, KS. A facile design and efficient synthesis of schiff's
bases of tetrazolo [1,5-a] quinoxalines as potential anti-inflammatory and anti-microbial
agents. Der Pharma Chemica, 2010; 2: 159-67.
28. Olayiwola, G, Obafemi, AC, Taiwo, OF. Synthesis and neuropharmacological activity
of some quinoxalinone derivatives. African Journal of Biotechnology, 2007; 6: 777-86.
29. Ali MM, Ismail MM. F., El-Gaby, MSA, Zahran MA, Ammar YA. Synthesis and
antimicrobial activities of some novel quinoxalinone derivatives. Molecules, 2000; 5:
864–73.
30. Ries UJ, Priekpe HW, Havel NH, Handschuh S, Mihm G, Stassen JM, Wienen W, Nar H.
Heterocyclic thrombin inhibitors. Part 2: quinoxalinone derivatives as novel, potent
antithrombotic agents. Bioorg. Med. Chem. Lett, 2003; 13: 2297–2302.
31. Osama SM. Synthesis of some new heterocycles of pharmaceutical interest: pyridinyl and
isoxazolyl quinoxaline derivatives. Journal of the chinese chemical society, 2003; 50:
1205-8.
32. Dharmchand PS, Sanjay KD, Syed RH, Ram GS. Synthesis and Antimicrobial activity of
some new quinoxaline derivatives. Pharmaceuticals, 2010; 3: 2416-25.
33. Chih-Hua T, You-Ren C, Cherng-Chyi T, Wangta L, Chon-Kit C, Chien-Chih C, Yeh-
Long, C. Discovery of Indeno[1,2-b]quinoxaline Derivatives as Potential Anticancer
Agents. European Journal of Medicinal Chemistry, 2015; 1-54. doi:
10.1016/j.ejmech.2015.11.031.
30
34. Hajri M, Esteve M, Khoumeri O, Abderrahim R, Terme T, Montana M, Vanelle P.
Synthesis and evaluation of in vitro antiprolife rative activity of new ethyl 3-(ar
ylethynyl) quinoxaline -2-carboxylate and pyrido[4,3- b] quinoxalin-1 (2 H )-one
derivatives. European Journal of Medicinal Chemistry, 2016; 124: 959-66.

Documents

A REVIEW ON BIOLOGICAL STUDIES OF QUINOXALINE …