Synthesis and Anti-Microbial Activity of Some

SYNTHESIS AND ANTI-MICROBIAL ACTIVITY OF SOME

NOVEL SUBSTITUTED QUNOLINE DERIVATIVES

M.Pharm. dissertation protocol

Submitted to the

Rajiv Gandhi university of health science, Bangalore,

Karnataka.

By

SARADE ANAND NAGANATH

B.Pharm.

Under the esteemed guidance of

Dr. N.V. Kalyane

M.Pharm. Ph.D.

Prof. and Head

Dept. of Pharmaceutical chemistry.

B.L.D.E.A’S COLLEGE OF PHARMACY, BIJAPUR

2008-2009

Rajiv Gandhi University of Health Sciences,

Bangalore, Karnataka.

ANNEXUURE II

PROFORMA FOR REGISTRATION OF SUBJECT OF DISSERTATION

I / Name and address of candidate / SARADE ANAND NAGANATH
B.L.D.E.A’S.COLLEGE OF PHARMACY,
POST BOX NO.40, B.L.D.E. UNIVERCITDY CAMPUS.BIJAPUR-586103
2 / Name of institution / B.L.D.E.A’S COLLEGE OF PHARMACY, BIJAPUR.
3 / Cource of study and subject / MASTER OF PHARMACY IN
PHARMACEUTICAL CHEMISTRY
4 / Date of addmition
To cource / 15-06-2009
5 / Title of topic / “SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME NOVEL SUBSTITUTED QUINOLINE DERIVETIVES”
6.  Brief resume of intended work
6.1 Need for study:
The most useful medical properties associated with these naturally occurring quinoline have lead to investigation of several synthetic analogue for such properties. This has resulted in voluminous work in this area. Several monograph on synthetic and natural quinoline have appeared in the literature. As background for present investigation a brief summary of natural and synthetic quinoline is given under.
A number of natural and synthetic quinoline are of considerable chemical and biological importance varius quinoline have displayed Anti-microbial1, Antibacterial2, And antifungal3, antiviral4,antimalarial5, etc. Most of drug derived from different hetero quinoline. Many natural product with useful medical properties have served as compound in drug development
In view of above fact quinoline have been investigated .The investigation of these derivatives as search for new drug or to increase efficacy of existing drug has been most common approach in recent year .It is expected that substitutes of this quinoline heterocyclic may result in clinically useful drug molecule
So in present study we plan to synthesize a simple rout for synthesis of some newer quinoline derivatives as bioactive compound with less toxic effect.
6.2 Review of literature:
Literature survey reveal that qunoline has received considerable attention during last two decade as they are endowed with variety of biological activities and wide range of therapeutic activities And some literature survey of present study is as under;’
·  Gopalkrishnan S. et al, studied the total acidity of the materials decreased after ion-exchange as revealed from TPD (ammonia) study. It also showed selective ion-exchange of strong acid sites by Ga3+, In3+, La3+ and Ce3+ ions. Their catalytic activity was tested in the solvent free synthesis of coumarin using resorcinol and ethyl acetoacetate in the liquid phase. Lewis acid ion-exchanged catalysts showed higher activity than the parent ZAPO-5. The Lewis acid metal ion could act as a template which brings the reactants to its co-ordination sphere and subsequently reacts to form coumarin6,
·  Kalagouda B. et al, developed a new Mannich base, [7-hydroxy-4-methyl-8-coumarinyl]glycine [MCGH2], prepared by the condensation of 7-hydroxy-4-methylcoumarin with glycine and formaldehyde. The antimicrobial activity of all the compounds was studied against Gram negative (Escherichia coli) and Gram positive (Bacillus cirroflagellosus) bacteria and fungi, Aspergillus niger and Candida albicans7,
·  Palanippan S. et al, studied polyaniline-sulfate salts were prepared using four different oxidizing agents such as benzoyl peroxide, ammonium persulfate, sodium persulfate and potassium dichromate. Polyaniline-sulfate salts were characterized by spectral, physical and electrical methods. Polyaniline base was redoped to different polyaniline salts using various acids. Polyaniline salts are used as polymer supported acid catalysts for the preparation of 7-hydroxy-4-methyl coumarin8,
·  Dinakaran V. et al, studied some new, 2,3-disubstituted quinazolin-4-(3H)-ones have been synthesized by the condensation of respective 2-substituted 1,3-benzoxazin-4-ones (4a-b) with different primary amines in equimolar conc. The structure of these compound have been established on the basis of their elemental, analytical and spectral data9,
·  Milan Cacic and Mladen Trkovnik synthesized (7-hydroxy-2-oxo-2H-chromen-4-yl) –acetic acid hydrazide from (7-hydroxy -2-oxo-2H-chromen-4-yl)-aceticacid ethyester and 100% hydrazine hydrate. The compound (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide is key intermediate for several series of new compound such as schiff’s bases,formic acid N’-[2-(7-hydroxy-2-oxo—2H-chromen-4-yl)acetyl hydrazide and like other derivatives which shows antimicrobial acivity10,
·  Mashooq A.Bhat and S.A.Khan synthesized some coumarin incorporated 1,3,4-oxadiazoles in wich salicylaldehyde and diethylmalonate were reacted in presence of piperridine in ethanolto form ethyl ester o f coumarin which upon treatment with hydrazine hydrat (99%)resulted in coumarin-3-carbonylhydrazide which has reacted with different aldehyde and ketones to form schiff’s bases which on cyclization in excess of acetic unhydride gave 4-acetyl-2-coumaryl-5-substituted -1,3,5-oxadiazol11,
·  P Vijaya Kumar and V Rajeswar Rao “synthesized 3-(3-mercaptoalkyl-7H-[1,2,4] triazol[3,4-b] [1,3,4]-thiadiazin-6-yl)chromen-2-one derivative has achived by condensation of 3-(2-bromoacetyl) coumarin with4-amino -5-mercaptoalkyl-4H-[1,2,4]-triazol-3-thiol in unhydrus ethanol reflux for 3 to 4 hr12,
6.3 Objectives :
The increasing clinical importance of drug resistance bactetial; and fungal pathogen has lent additional urgency to anti microbial research and development of new anti bacterial compound .Hence we planeed in present objectives of study will be as below.
1  To developed a simle synthetic method for synthesis of titled compound
2  Chemical characterization of newely synthesized compound by I.R, NMR, and mass spectral data
3  Screening for Anti-microbial activity
MATERIAL AND METHOD
7.1  source of data
The present project is synthesis and chemical characterization of some novel benzoxazole derivatives and their biological evaluation. All chemical required for synthesis were purchase from Aldrich, fluka and SD fine chemicals etc, through college funds. The subject will be studied in detail by referring national and international journals in medicinal chemistry. Our college has E-library facility to browse all the journals and also college providing the necessary financial assistance for the student to visit library at IICT Hyderabad and IISC, bangalore for the literature survey.
Scheme for synthesis of proposed work
Resorcinol + Ethyl acetoacetate

7-hydroxy-4-methylcoumarine
+
Sulphonamide

1-{4-[(aminooxy)sulfinyl]phenyl}-7-hydroxy-4-methylquinolin-2(1H)-one
+
R-CHO

Derivatives of Quinoline
7.2  Method of collection of data
The chemical structures of the synthesized compounds will be established on the bases of physical, chemical and analytical data. Purification of the synthesized compounds will be done by using recrystallization techniques. Melting point of the newly synthesized compounds will be analyzed by using open capillary tube method.
The chemical characterization of the newly synthesized compounds will be confirmed by IR, NMR and Mass spectral data.
Antimicrobial activity of newly synthesized compound will be tested by using disc diffusion method by using varius Gram positive and Gram negative organism and this activity will be carried out in our laboratory
7.3  Does the study require any investigstion tobe conducted on patient or humans or animals?If so, please describe briefly.
NOT APPLICABLE
7.4  Has ethical clearance been obtained from your institution in case of 7.3?
NOT APPLICABLE
8. References:-
1. Mamledesai S.N., Katagi M.S., Khare P.V., Maddi, Bhat A.R. Synthesis and antimicrobial activity of 4-hydroxy-1-methyl/phenyl-3-substituted qunoline-2-(1H)-one. Ind J of het chem. 2008; 17: 381-82.
2. Rajesh K., Reddy B.P., Vijaykumar V. Synthesis and biological evaluation of 4-(4-(DI-(1H-indol-3-yl)methyl)phenoxy)-2-chloroqunolines. Ind J of het chem. 2009;19:95-96
3. Revanasiddappa B.C., Subrahmanyam E.V.S., Satyanarayan D. synthesis and biological evaluation of 2-aryl-5(8_qunolinoxymethyl)1,3,4-oxadiazoles. Ind J of het chem. 2009; 18: 403-04.
4. Ganguly S., Murugesan S., Maga G. Synthesis, evaluation and molecular modeling studies of some novel tetrahydroisoqunoline derivatives targated at the HIV-1 reverse transcriptase. Ind J of het chem. 2009; 18: 357-60
5. More U.B., Narkhede H.P., Raut C.N., Mahulikar P.P. Polymer supported synthesis of bioactive heterocyclic compound. Ind J of het chem. 2009; 19: 43-46
6. Gopalkrishna S., Viswanathan K.R., Vishnu Priya S., Herbert Mabel J., Palanichamy M., Murgesan V. “Synthesis of 7 hydroxy-4-methyl coumarin over lewis acid metal ion exchanged ZAPO-5 molecular sieves” Microporous and Mesoporous Materials 2009; 118: 523-530.
7.  Gudasi K.B., Patil M.S., Vadavi R.S. “Synthesis of characterization of copper(II), cobalt (II), nickel (II), zinc and cadmium (II) complex of [ 7 hydroxy-4-methyl-8-coumarinyl] glucine and a comparative study of their microbial activities” Eur J of med chem 2008; 43: 2436-2441.
8.  Palagouda S., Chandra Shekhar R. “ Synthesis of 7 hydroxy -4-methyl coumarin using polyaniline supported acid catalyst” J of mol catalyst A:chemical 2004; 209: 117-124.
9.  Dinakaran v., Unnissa H., Kalishwari E. “Synthesis and antibacterial activity of 2,3-disubstitutted quinazolin-4(3H) ones” Ind J of het chem 2008; 17: 347-350.
10.  Cacic M, Trkovnik M., Cacic F. & Has-Schon E. “Synthesis & antimicrobial activity of some derivative of (7-hydroxy-2-oxo-2H-chromen-4-yl) acetic acid hydrazide”.Molecules 2006; 11:134-147.
11. Bhat M. A., Khan S. A. and Siddiqui N. ”Synthesis & antibacterial activity of coumarin
Incorporated 1,3,4-oxadiazole”. Ind. J of het chem 2005; 271-272.
12. Vijaya Kumar P., V. Rajeshvar Rao. “Synthesis & anti tubercular, anticancer
activity of 3-93-mercaptoalkyl-7-H-[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazine-6-yl)chromen-
2-one & its derivatives” Ind.J.of Chem 2008; 106-11.
9. / Signature of Candidate / [ANAND NAGANATH SARADE]
10. / Remarks of the Guide / .
11. / Name & Designation of (in block letters)
11.1 / Guide / Dr. N.V. KaLYANE
M.Pharm., Ph.D..
PROFESSOR & HEAD
DEPT. OF PHARACEUTICAL CHEMISTRY
B.L.D.E.A’s COLLEGE OF PHARMACY, BIJAPUR
11.2 / Signature
11.3 / Co-Guide:
11.4 / Signature
11.5 / Head of Department / Dr. N.V. KaLYANE
M.Pharm., Ph.D..
PROFESSOR & HEAD
DEPT. OF PHARMACEUTICAL CHEMISTRY
B.L.D.E.A. COLLEGE OF PHARMACY, BIJAPUR.
11.6 / Signature
12. / 12.1 / Remarks of the Chairman & Principal
12.2 / Signature / (Dr.N.V. KALYANE)