“SYNTHESES, CHARACTERIZATION OF SOME NEW CONDENSED PYRIDINE-2-ONES AND FURANS FOR IN-VITRO ANTI-TUBERCULAR AND ANTI-OXIDANT ACTIVITY”
SYNOPSIS FOR
M.PHARM.DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
LAKSHMI.Y
I M.PHARM
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
PES COLLEGE OF PHARMACY
BANGALORE-560 050
(2009-2011)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of the candidate and address / LAKSHMI.Y1st M. PHARM (PHARMACEUTICAL CHEMISTRY)
PES COLLEGE OF PHARMACY
50 FEET ROAD,
HANUMANTHANAGAR,
BANGALORE-560 050
PERMANENT ADDRESS:
D/O MAHADEVAPPA.Y
NO:153 , IV CROSS LEFT,
G.K.W.LAYOUT
VIJAYANAGAR
BANGALORE-560 040.
2. / Name of the institution / PES COLLEGE OF PHARMACY
50 FEET ROAD,
HANUMANTHANAGAR
B.S.K.1st STAGE
BANGALORE:-560 050.
3. / Course of the study / MASTER OF PHARMACY
(PHARMACEUTICAL CHEMISTRY)
4. / Date of Admission / 19th June- 2009
5. / Title of the topic:
“SYNTHESES, CHARACTERIZATION OF SOME NEW CONDENSED PYRIDINE-2-ONES AND FURANS FOR IN-VITRO ANTI-TUBERCULAR AND ANTI-OXIDANT ACTIVITY”
OXOQUINOLINE TETRAHYDROBENZOFURAN
The labile aminogroup will be reacted with different acid chlorides , aldehydes , chloro acetyl chloride, acetic anhydride and so on to obtain the desired title compounds.
6. / Brief resume of the intended work
6.1 Need for the study
Oxoquinolines have been reported to possess an assortment of pharmacological properties including anti-inflammatory, analgesic, anticancer & biological activities including antibacterial, anti-tubercular, antifungal, antiviral and so on. Tetrahydrobenzofurans are also very well known to the research field for their versatile pharmacological activities. As a result of remarkable pharmacological efficiency of Oxoquinoline and Tetrahydrobenzofuran derivatives, intensive research has been focused on anti-tubercular and anti-oxidant activity of the above mentioned nucleus.
The following are some of the Oxoquinoline and Tetrahydrobenzofuran derivatives found to possess the above mentioned activities:
Scheme: 1
1. 4-(3,4-difluorophenyl)oxazolo[4,5-c]quinolin-2-amine.
2. 6-sulfamoyl-4-oxoquinoline-3-carboxylic acid.
3. 1-(substituted)-1,4-dihydro-6-nitro-7-(substituted secondary amino)-4-oxoquinoline-3-carboxylic acid.
4. 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-thiomorpholino-1,4-dihydroquinoline-3-carboxylic acid.
5. 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid.
6. 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid.
7. N-[p-{3'-(2'-aryl-4'oxo-1',3'-thiazolyl)}diphenyl]-7-hydroxy-4-methyl-2-oxoquinoline.
8. 6-fluoro-1-(4-fluorophenyl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4,4a,8a-tetrahydroquinoline-3-carboxylic acid.
9. 2-(4-methyl-2-oxoquinolin-1-(2H)-yl)acetic acid.
Scheme:2
1. 5-(6-hydroxy-7-(3-methylbut-2-enyl)benzofuran-2-yl)benzene -1,3-diol.
2. 2-(3,4-dihydroxybenzylidene)-4,6-dihydroxy benzofuran-3-one.
3. 1-(1-benzofuran-2-yl)-2-mesitylethanone.
4. 5,6-dihydroxy-2-methyl-1-benzofuran-3-carboxylate derivatives.
5. 5,7-di-tert-butyl-3-p-tolylbenzofuran-2(3h)-one.
6. aryl[(3-imidazol-1-yl)benzofuran-2-yl]ketoxime.
7. aryl(benzofuran-2-yl)ketoxime acetate.
8. 6-(benzofuran-2-yl)-7-methoxybenzo[d][1,3]dioxol-5-ol.
Oxoquinoline:
1 2
3 4
5 6
7 8
9
Benzofuran:
1 2
3 4
5 6
7 8
In the view of the above observations it was thought of interest to synthesize and screen some new oxoquinoline and Tetrahydrobenzofuran derivatives for in-vitro anti-tubercular and anti-oxidant screening. The successful scheme will be reported in the thesis.
6.2 Review of the literature:
Oxoquinolines:
v Eswaran S, et al., reported the new 1,3-oxazolo[4,5-c]quinoline derivatives: Synthesis and evaluation of antibacterial and antituberculosis properties(1).
v Luo ZG, et al., reported the synthesis of 6-sulfamoyl-4-oxoquinoline-3-carboxylic acid derivatives as integrase antagonists with anti-HIV activity(2) .
v Senthilkumar P, et al., reported the synthesis and anti mycobacterial activities of novel 6-nitroquinolone-3-carboxylic acids(3).
v Senthilkumar P, et al., reported the synthesis and antimycobacterial evaluation of newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondaryamino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids(4).
v Dinakaran M, et al., reported the antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid(5).
v Almeida MVd, et al., reported the synthesis and antitubercular activity of lipophilic moxifloxacin and gatifloxacin derivatives(6).
v Bishnoi A, et al., repoted the synthesis ,characterization and in-vitro anti-JEV activity of N-[p-{3'-(2'-aryl-4'oxo-1',3'-thiazolyl)}diphenyl]-7-hydroxy-4-methyl-2-oxoquinolines(7).
v Mitscher LA, et al., reported the synthesis and Antimicrobial Activity of the Enantiomers of 6-Fluoro-7-( 1-piperaziny1)- 1-(2'-trans -phenyl-1'-cyclopropy1)-1,4-dihydro-4-oxoquinoline-3-carboxyllic acid(8).
v DeRuiter J, et al., reported the synthesis and Aldose Reductase Inhibitory Activity of Substituted 2- Oxoquinoline- 1 -acetic Acid Derivatives(9).
Benzofurans:
v Kapche GDWF, et al., reported the prenylated arylbenzofuran derivatives from Morus mesozygia with antioxidant activity(1).
v Detsi A, et al., reported the natural and synthetic 20-hydroxy-chalcones and aurones: Synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity(2).
v Kirilmis C, et al., reported the synthesis and antimicrobial activity of some novel 1-(1-benzofuran-2-yl)-2-mesitylethanone derivatives(3).
v Fakhari AR, et al., reported the electrochemical synthesis of 5,6-dihydroxy-2-methyl-1-benzofuran-3-carboxylate derivatives(4).
v Meng X, et al., reported the study on the antioxidant activities of benzofuranones in melt processing of polypropylene(5).
v Gündoğdu-Karaburun N, et al., reported the synthesis and antifungal activities of some aryl[3-(imidazol-1-yl/triazol-1-ylmethyl) benzofuran-2-yl] ketoximes(6).
v Demirayak Se, et al., reported the synthesis and antifungal activities of some aryl(benzofuran-2-yl)ketoximes(7).
v Jinno S, et al., reported the synthesis of an anti-oxidant isolated from yeast via palladium-catalyzed coupling and its application for related compounds(8).
6.3 Objectives of the study
1. To achieve the synthesis of some novel Oxoquinolines and Tetrahydrobenzofurans.
2. The purity and progress of the reactions will be monitored by micro TLC.
3. The purification of the compounds will be carried out by recrystallization by suitable solvents.
4. To characterize the structures of new compounds by UV, IR, NMR and MASS spectra.
5. To evaluate the in-vitro anti-anti-tubercular and ani-oxidant activity of the new compounds to study the structure-activity relationships and to optimize the structure.
6. To publish the research work in peer reviewed journals.
7. / 7.1 Materials and methods:
Chemicals and other reagents will be purchased from standard companies. The progress of the reactions will be monitored by micro thin layer chromatography. The standard protocols will be followed for purification of the products. Structures of the synthesized molecules will be confirmed by the analytical and spectral data. The in-vitro anti-tubercular and anti-oxidant screening results will be used to study structure-activity relationships.
7.2 Sources of data:
IISc library, Bangalore.
PESCP library, Bangalore.
RGUHS Digital library(Helinet).
Central College library, Bangalore.
7.3 Method of collection of data
Chemical Abstracts, Journals like Indian Journal of Chemistry, Journal of Medicinal Chemistry, Indian Journal of Heterocyclic Chemistry, Neurochemistry International, Indian Journal of Pharmaceutical Sciences, Journal of Organic chemistry, European Journal of Medicinal Chemistry, Bioorganic & Medicinal Chemistry, Bioorganic & Medicinal Chemistry Letters, Tetrahedron Letters, Asian Journal of Chemistry and Helinet.
7.4 Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
-NO-
7.5 Has ethical clearance been obtained from your institution in
case of 7.4?
-NO-
8 / References:
Oxoquinolines:
1. Eswaran S, Adhikari AV, Kumar A. New 1,3-oxazolo[4,5-c]quinoline derivatives: Synthesis and evaluation of antibacterial and antituberculosis properties. Eur J Med Chem. 20 November 2009.
2. Luo ZG, Zeng CC, Yang LF, He HQ, Wang CX. Synthesis of 6-sulfamoyl-4-oxoquinoline-3-carboxylic acid derivatives as integrase antagonists with anti-HIV activity. Chin J Chem Lett 2009; 20: 789–92.
3. Senthilkumar P, Dinakaran M, Yogeeswari P, Sriram D, China A, Nagaraja. V. Synthesis and antimycobacterial activities of novel 6-nitroquinolone-3-carboxylic acids. Eur J Med Chem. 2009; 44 345-58.
4. Senthilkumar P, Dinakaran M, Banerjee D, Devakaram RV, Yogeeswari P, China A, et al. Synthesis and antimycobacterial evaluation of newer1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondaryamino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids. Bioorg Med Chem 2008; 16 2558–69.
5. Dinakaran M, Senthilkumar P, Yogeeswari P, China A, Nagarajaa V, Srirama. D. Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylicacid. Bioorg Med Chem 2008;16: 3408–18.
6. Almeida MVd, Saraiva McF, Souza MVNd, Costa CFd, Vicenteb FRC, Lourenc. MCS. Synthesis and antitubercular activity of lipophilic moxifloxacin and gatifloxacin derivatives. Bioorg Med Chem Lett 2007; 17 5661–4.
7. Bishnoi A, Srivastava k, Joshi MN. Synthesis ,characterization and in-vitro anti-JEV activity of N-[p-{3'-(2'-aryl-4'oxo-1',3'-thiazolyl)}diphenyl]-7-hydroxy-4-methyl-2-oxoquinolines. Indian J chem 2006;45B:1961-4.
8. Mitscher LA, Sharma tPN, Chu tDTW, Shen LL, Pernett AG. Chiral DNA Gyrase Inhibitors. 1. Synthesis and Antimicrobial Activity of the Enantiomers of 6-Fluoro-7-( 1-piperaziny1)- 1-(2'-trans -phenyl- 1'-cyclopropy1)-1,4-dihydro-4-oxoquinoline-3-carboxyllic acid. J Med Chem. 1986; 29 2044-7.
9. DeRuiter J, Brubaker AN, Whitmer WL, Stein. JL. Synthesis and Aldose Reductase Inhibitory Activity of Substituted 2- Oxoquinoline- 1 -acetic Acid Derivatives. J Med Chem. 1986;29: 2024-8.
Benzofurans:
1. Kapche GDWF, Fozing CD, Donfack JH, Fotso GW, Amadou D, Tchana AN, et al. Prenylated arylbenzofuran derivatives from Morus mesozygia with antioxidant activity. Phytochem 2009; 70 216–21.
2. Detsi A, Majdalani M, Kontogiorgis CA, Hadjipavlou-Litina D, Kefalas. P. Natural and synthetic 20-hydroxy-chalcones and aurones: Synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity. Bioorg Med Chem 2009;17:8073–85.
3. Kirilmis C, Ahmedzade M, Servi Sl, Koca M, Kizirgil A, Kazaz. C. synthesis and antimicrobial activity of some novel 1-(1-benzofuran-2-yl)-2-mesitylethanone derivatives. Eur J Med Chem 2008;43: 300e8.
4. Fakhari AR, Nematollahi D, Shamsipur M, Makarem S, Davarani SSH, Alizadehd A, et al. Electrochemical synthesis of 5,6-dihydroxy-2-methyl-1-benzofuran-3-carboxylate derivatives. Tetrahedron 2007;63: 3894–8.
5. Meng X, Gong W, Xin Z, b. ZC. Study on the antioxidant activities of benzofuranones in melt processing of polypropylene. Polym Degrad Stab. 2006;91: 2888e93.
6. Gündoğdu-Karaburun N, Benkli K, Tunali Y, Uçucu Ü, Demirayak. Ş. Synthesis and antifungal activities of some aryl[3-(imidazol-1-yl/triazol-1-ylmethyl) benzofuran-2-yl] ketoximes. Eur J Med Chem 2006;41: 651–6.
7. Demirayak Se, Uc¸ucu Um, Benkl K, Gu¨ndog˘du-Karaburun N, Karaburun ACar, Akar D, et al. Synthesis and antifungal activities of some aryl(benzofuran-2-yl)ketoximes. Il Farmaco 2002;57: 609–12.
8. Jinno S, Okita T, Inouye. K. Total synthesis of an anti-oxidant isolated from yeast via palladium-catalyzed coupling and its application for related compounds. Bioorg Med Chem Lett. 1999;9: 1029-32.
9 / Signature of the candidate : / [LAKSHMI.Y]
10. / Remarks of the guide: / FORWARDED WITH A REQUEST FOR APPROVAL
11. / Name and designation of:
11.1 GUIDE
11.2 SIGNATURE / Dr. J. Saravanan
Prof. and Head
Department of Pharm Chemistry,
PES College of Pharmacy
Bangalore- 560 050
11.3 CO-GUIDE
11.4 SIGNATURE / ------NIL------
11.5 HEAD OF THE DEPARTMENT
11.6 SIGNATURE / Dr. J. Saravanan
Prof. and Head
Department of Pharm Chemistry,
PES College of Pharmacy
Bangalore- 560 050
12. / 12.1 REMARKS OF THE PRINCIPAL: FORWARDED FOR APPROVAL
12.2 SIGNATURE: Prof. Dr. S. Mohan
Director Principal,
PES College of Pharmacy
Bangalore-560 050
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