SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME SUBSTITUTED 4-METHYL 2-QUINOLONES

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

BY
SUNIL KUMAR.U.S
M.PHARM, PART- I

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

UNDER THE GUIDANCE OF

Mr. M.CHANDRASHEKAR, M.PHARM

Department Of Pharmaceutical Chemistry

Dr.H.L.T College of Pharmacy,

Kengal, Channapatna-571502

2007

Rajiv Gandhi University of Health Sciences, Bangalore

Karnataka

AnneXUre II

Proforma for Registration of subjects for Dissertation

1. / Name of the Candidate and
Address (in Block Letters) /

SUNIL KUMAR. U.S

M. PHARM, PART-I
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY.
Dr. H. L. T.COLLEGE OF PHARMACY.
KENGAL, CHANNAPATNA-571502
BANGALORE (RURAL), KARNATAKA.
2 / Name of the Institution / Dr. H. L. T. College of Pharmacy
Kengal, Channapatna,
Bangalore Rural 571 502
3 / Course of the Study and Subject /

Master of Pharmacy in Pharmaceutical Chemistry.

4 / Date of Admission to the Course / 04/06/2007
5 /

Title of the Topic

/ “SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME SUBSTITUTED 4-METHYL 2-QUINOLONES ”

6  BRIEF RESUME OF THE INTENDED WORK

6.1  NEED FOR THE STUDY

Quinoline derivatives are an important class of compounds that has attracted attention as a source of new antibacterial agent1. Studies in the synthesis and biological activities of quinalones and their derivatives gained sufficient momentum especially after discovering the antimalarial alkaloid from the chines plant febrifuge, which was a 4-quinalones. Many derivative show hypnotic and anticonvulsant activity and diuretic have established their firm footing in medicinal chemistry. Substituted quinoline derivative were studied for antimalarial activities by suitably modifying the molecular structure of febrifuge.

Gram positive and Gram-negative organisms have re-emerged as the major hospital pathogens. The limitations of many antibiotics such Penicillin, Vanomycin, Oxazolidinone linezolid, etc have been documented. The Current antibiotic cupboard is rather bare for meeting the challenge of new outbreaks of such resistant bacteria. There is an urgent medical need for new antibacterial agent with improved profile against pathogens.

Flouroquinolones antibacterials are among the most attractive agents in the treatment of bacterial infections since the discovery of norfloxacin. However, despite many advances achieved in flouroquinolones, research during the last several decades, the current qionolones have low intrinsic activity against a number of pathogens.

With view of these facts, our attention is drawn towards synthesis of 4-methyl 2 quinalones derivative as Antibacterial agents.

6.2. REVIEW OF LITERATURE

Extensive literature survey was carried out in the library of Dr.H.L.T. College of Pharmacy, Channapatna, IISC, Bangalore and Visiting various web sites through inter net the relevant data has been collected.

Ø  D.L.Leysan, A.Haemers and W.Bollaert worked on synthesis of some 2,4-disubstituted derivatives of Quinolone-3-carboxylic acid and corbonitriles1

Ø  S.N. Mamledesai et al, worked on synthesis and antifungal activity of 3-alkylaryl amino methyl-4-hydroxy-1-phenyl-2(1H) Quinolones2.

Ø  Y.K. Agarwal and Hardik M. Joshipura, reported condensation of 3-acetyl-4-aryl-2-oxyquinolines with ethyl acetate3.

Ø  Zhenfa Zhang et al; worked on synthesis and structure activity relationship of 7-(substituted) amino methyl-4-quinolone-3-carboxylic acid derivatives4.

6.3.  MAIN OBJECTIVES OF THE STUDY

The objectives of proposed study are:

·  New substituted 4-methyl-2-Quinolones will prepared by using P-Phenyline di-amines, Ethyl acetate, Sodium nitrite, Hydro Chloricacid etc are having better anti microbial activity.

·  Characterizes, identify, quantify, purify the synthesized compounds by thin layer chromatography, melting point determination by Thiels melting point tube (capillary tube method), Infrared Spectroscopy, Nuclear Magnetic Resonance Spectroscopy and Mass Spectroscopy.

·  To screen these newly synthesized compounds for anti microbial activity for various Gram +ve and Gram –ve bacteria.

7.  MATERIALS AND METHODS

7.1 SOURCE OF DATA

The preliminary data required for the experimental study was obtained from

CD-Rom search available at National Center for Scientific Information (NCSI). Chemical Abstract.

Scientific Journals.Dr. H.L.T. college of Pharmacy Library, Indian institution of sciences (IISC). Bangalore, Internet Source

7.2.  METHODS OF COLLECTION OF DATA

A)  Synthetic Studies:

To synthesize proposed target compounds by appropriate methods as per the following scheme: -

P-phenyline di-amines +ethyl aceto acetate

Condensation

6-amino,4-methyl-Quinoline-2-one

Diazotization

Di azo 4-methyl- Quinoline-2-one

Substituted –4-methyl-Quinoline-2-one

B)  Biological screening:

Antibacterial activity will be carried out by zone of inhibition studies by cup plate method.

7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so please describe briefly.

The study does not require any investigations on patients or humans or animals.

7.4  Has ethical clearance been obtained from your institution in case of 7.3.

……………………..Not Applicable………………………………………..

8.  LIST OF REFERENCES

  1. D.L.Leysen, A.Haemers and W.Bollaert. The Synthesis of some 2,4-Sisubstitued Derivatives of Quinolone-3-Carboxlyic acids and Carbonitriles, Indian journal of Heterocyclic Chemistry, 1987;Nov-Dec 24:1611.
  1. S.N.Mamledesai.et.al., Synthesis and Antifungal activity of 3-Alkyl Aryl Aminomethyl-4-Hydroxy-1-phenyl-2(1H) Quinalones, Indian Journal of Heterocyclic chemistry., 2007; April-June 16: 407-408.
  1. Y.K.Agarwal and Hardik M Joshipura, Reported Condensation of 3-acetyl-4-aryl-2-oxyquinolones with ethyl acetate, Indian Journal of Chemistry. 2005 August, 44 B: 1649-1652.

4.  Zhenfa Ahang, et.al., Synthesis and structural activity relationship of 7-(substituted)-aminomethyl-4-quinalone-3-carboxlic acid derivatives. Bioorganic and medical chemistry, 2007 .15: 7274-7280.

5.  David A. Williams, Thomas L.Lemke, Foeye’s Principles of medicinal chemistry, 5th Ed, Lippincott Williams and Wilkins publication. New Delhi, 2002:825-850.

6.  John H Block et.al., Wilson and Gisvold’s Text book of organic medicinal and Pharmaceutical chemistry. 11th Ed, Lippincott William and Wilkins. New York, 2004: 247-252.

7.  Jerry march, Advanced organic chemistry 4thEd, John Willey and Sons, Newyork,1992: 890-897.

8.  K.D.Tripathi, Essentials Of Medical Pharmacology. 5th Ed, Jaypee brothers, New Delhi.2003: 646-652.

9.  Goodman and Gilman’s, The pharmacological basis of therapeutics. 10th Ed, Mc graw-Hill, New York. 2001:1179-1185.

  1. Hobart H.Willard, Lynne L.merit, Jr.John A.Dean, Frank A, Settle, Jr.Instrumental Method Of Analysis. 7th Ed, Wads Worth publishing company, California.1988: 465-505.

9 / Signature of the candidate
10 / Remarks of the Guide / Topic selected for Dissertation work is satisfactory. This can be carried out in our Laboratory.
11 / Name and Designation of
(In Block Letters)
11.1  Guide
11.2  Signature / Mr. M. CHANDRASHEKAR M. Pharm
PROFESSOR
DEPT. OF PHARMACEUTICAL CHEMISTRY.
Dr. H. L. T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-571 502
BANGALORE (RURAL), KARANATAKA.
11.3  Co – Guide
(If any)
11.4  Signature
11.5  Head of the Department
11.6 Signature / Mr. M. GURUMURTHY.M. Pharm
ASSISTANT PROFESSOR
DEPT. OF PHARMACEUTICAL CHEMISTRY.
Dr. H. L. T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-571 502
BANGALORE (RURAL), KARANATAKA.
12 / 12.1  Remarks of the Chairman and Principal
12.2  Signature / The above mentioned information is correct and recommend the same for approval.

From

SUNIL KUMAR.U.S

M.Pharm, Dept.of Pharmaceutical Chemistry,

Dr.H.L.T College of Pharmacy,

Kengal, Channapatna.

To

The Registrar (Evaluation),

Rajiv Gandhi University of Health Sciences,

4th ‘‘T’’ Block, Jayanagar,

Bangalore-560 041

(Through Proper Channel)

Respected Sir,

Sub: Submission of Synopsis of Dissertation

Herewith, I am submitting synopsis of dissertation work “SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME SUBSTITUTED 4-METHYL 2-QUINOLONES” for registration in M.Pharm (Pharmaceutical chemistry) of Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka.

Kindly accept the same and oblige.

Thanking you,

Yours faithfully,

Place: Channapatna (SUNIL KUMAR.U.S.)

Date:

Guide:

Mr. M.CHANDRASHEKAR, M.Pharm

DEPT. OF PHARMACEUTICAL CHEMISTRY PRINCIPAL

Dr. H.L.T.College of Pharmacy, Dr. H.L.T.College of Pharmacy, Kengal, Channapatna Kengal, Channapatna.

Bangalore (Rural)-571 502 Bangalore (Rural) 571 502