SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF
SOME NOVEL
BIS-2-AZETIDINONES.
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA.
BY
CHAITRA.A
I M. PHARM
Department of Pharmaceutical Chemistry
M. S. Ramaiah College of Pharmacy
BANGALORE – 560 054
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE. KARNATAKA
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS
FOR DISSERTATION
1.0 / NAME OF THE CANDIDATE AND ADDRESS / CHAITRA.ANo. 4566.Behind Dwaraka plaza,
B.H.Road. Nelamangala.
BANGALORE – 562 123.
2.0 / NAME OF THE INSTITUTION / M. S. RAMAIAH COLLEGE OF PHARMACY
M.S.R. NAGAR, M.S.R.I.T. POST,
BANGALORE – 560 054
3.0 / COURSE OF STUDY AND SUBJECT / M. PHARM
PHARMACEUTICAL CHEMISTRY
4.0 / DATE OF ADMISSION / 9th JUNE 2007
5.0 / TITLE OF TOPIC / SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME NOVEL
BIS-2-AZETIDINONES.
6.0 / BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR PRESENT STUDY
Design and synthesis of heterocyclic compounds by simple environment friendly methods will have a direct impact on the health and well being of human and other living creatures. The modern heterocyclic chemistry relates the importance and structural diversities of azetidinones and other related nucleus.
2-Azetidinones, commonly known as β-lactams are well known heterocyclic compounds among the organic and medicinal chemists.1 The activity of famous antibiotics like Penicillins, Cephalosporins and Carbapenems are attributed to the presence of 2-azetidinone ring in them.
Recently, some other types of biological activity besides the anti bacterial activity have been reported in compounds containing 2-azetidinone ring.2 Such pharmacological activities like anti-fungal, anti-tubercular,anti-microbial,2,3 anti-inflammatory, anti-convulsant,4 inhibitors of cholesterol absorption 5 etc.
Therefore, in this study, a strategy has been planned to synthesize newer bis-2-
azetidinones and screening for antibacterial and antifungal activities as per standard
methodology by the use of bacterial strains like S. aureus, E. coli, B. subtilis etc
and fungal strains like C. albicans, and A. niger respectively.
6.2 REVIEW OF LITERATURE
· Synthesis of azetidinone and thiazolidinone derivatives of pyrazinoic acid for possible anti-tubercular, anti-fungal and anti-bacterial activity was reported.2
· Synthesis of some new 2-azetidinones as potential anti-microbial agents was reported.3
· Synthesis of some new 1,2,4-triazolo-thiadiazoles and its 2-oxo azetidines as anti-microbial, anti-convulsant, anti-inflammatory agents was reported.4
· Synthesis of C3 hetero atom substituted azetidinones that display potene cholesterol absorption inhibitory activity was reported.5
· Synthesis and anti-microbial activity of heterocyclic Schiff bases,4-thiazolidinones and 2-azetidinones was reported.6
· Synthesis of some new 4-(N,N'-dimethyl-amino-sulfonyl-phenyl)-3-chloro phenyl azetidine 2-ones was reported.7
· Synthesis and biological evaluation of 4-(substituted aryl)-1-N-indolyl acetamido)-3-chloro-2-azetidinone was reported.8
· Synthesis and biological activity studies of some thiazolidinones and azetidinones was reported.9
· Synthesis and anti-bacterial activity of 4-oxo-thiazolidines and 2-oxo-azetidines was reported.10
· Synthesis of O-benzyl azetidinone derivatives of (R) and (S) 2-amino butanols was reported.11
· Bisheterocyclic synthesis and anti-microbial studies on some biologically significant 2-[N-(3'-chloro-4'-substituted azetidinone-2)]-amino-4-hydroxy purines was reported.12
· Thermally induced isomerisation of cis-1,3,4-tri-substituted 2-azetidinones was reported.13
· Synthesis of some new azetidine-2-ones as potential anti-microbial agents was reported.14
· Design, synthesis and in vitro anti-bacterial studies of some biologically significant N-3-chloro-4-[2-hydroxy-5-(phenyl azo)phenyl]azetidine-2-ones was reported.15
· Synthesis and anti-microbial screening of N-[6'-coumarinyl amino-3-chloro-4-arly]azetidine-2-ones was reported.16
· Convenient synthesis and biological activity of 2-azetidinones and 4-thiazolidinones was reported.17
· Synthesis and pharmacological activity of some azetidinones bearing Ibuprofen moiety was reported.18
· Synthesis and biological evaluation of some new azetidinones and thiazolidinones was reported.19
· Synthesis of novel bisquinazolinyl β-lactams was reported.20
· Synthesis of 4-thiazolidinones and 2-azetidinones bearing benzo(b)thiophene nucleus possessing anti-tubercular, anti-microbial activity was reported.21
· Synthesis of 2-azetidinones and other heterocycles from N-(3-hydroxy propyl)imines was reported.22
· Synthesis and biological activity of 2-azetidinones, 4-thiazolidinones, 5-imidazolinones having benzthiozole moiety was reported.23
· Rapid and efficient synthesis of some biologically active 2-azetidinones under microwave irradiation was reported.24
· Synthesis and biologically activity of some new Schiff bases, thiazolidinones and azetidinones of 4-hydroxy coumarin was reported.25
· Chemo enzymatic synthesis of chiral 3-hydroxy azetidine-2-ones was reported.26
6.3 AIMS AND OBJECTIVES OF STUDY
· To synthesize the title compounds using some simpler techniques.
· The synthesized compounds will be purified by the standard purification
methods like recrystalization and chromatographic methods.
· The new compounds synthesized will be characterized by using spectral
and analytical data like IR, NMR, Mass spectroscopy etc and elemental
analysis.
· These new compounds will be subjected to screening for anti-microbial
properties.
7.0 / MATERIALS AND METHODS:
7.1 SOURCE OF DATA
1. Literature survey, Internet searches in web sites:
www.google.com, www.pubmed.com, www.jhchem.com.and Chemical
Abstracts.
2. Journals and Publications like Indian journal of chemistry, Indian journal of
Pharmaceutical sciences, Indian journal of Heterocyclic chemistry, Indian
Journal of Medicinal chemistry, Tetrahedron letters etc.
7.2 METHOD OF COLLECTION OF DATA
· SYNTHESIS OF THE COMPOUNDS:
Chemicals and other reagents required for synthesis will be produced from standard company.
Compounds will be synthesized by using standard techniques and also by the use of microwave irradiation. TLC will be used to monitor the reaction at various stages. Purification of the compound will be done by employing techniques like Column Chromatography.
· CHARACTERIZATION OF THE COMPOUNDS:
The synthesized compounds will be characterized by preliminary laboratory techniques such as melting point, boiling point etc. Compounds synthesized will be confirmed by FTIR, Mass Spectroscopy and NMR spectral data.
· SCREENING OF ANTIMICROBIAL ACTIVITY:
(1) SCREENING OF ANTIBACTERIAL ACTIVITY BY DISC DIFFUSION METHOD: 27
Screening will be carried out on both Gram positive and Gram negative organisms like Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis etc using sterile Media like Mueller-Hinton Agar etc by Disc Diffusion Method. Zone of inhibition of the compounds synthesized will be noted and compared with that of standard drugs like Amoxicillin, Ciprofloxacin etc.
(2) SCREENING OF ANTIFUNGAL ACTIVITY BY DISC DIFFUSION METHOD: 27
Screening will be carried out on organisms like Candida albicans and Aspergillus niger using Media like Sabouraud Dextrose Agar. Zone of inhibition of the compounds synthesized will be compared with that of standard drugs like Clotrimazole.
The entire work will be done using Horizontal Laminar Flow hood.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON THE PATIENTS OR OTHER HUMAN/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
8.0 / LIST OF REFERENCES
1. Foye WO, Lemke TL, Williams DA. Principles of medicinal chemistry.4th edition. New Delhi. BI Waverly pvt ltd.1995.
2. Govindarajan R, Jameela HJ, Bhat AR. Synthesis of azetidinone and thiazolidinone derivatives of pyrazinoic acid for possible anti-tubercular, anti-fungal, anti-bacterial activity. Indian J heterocycl chem.2003; 12: 229-232.
3. Oza HB, Datta NJ, Joshi DG, Parekh HH. Synthesis of some new 2-azetidinones as potential anti-microbial agents. Indian J heterocycl chem.2003; 12: 275-276.
4. Srivastava SK, Srivastava S, Srivastava SD. Synthesis of new 1,2,4-triazolo-thiadiazoles and its 2-oxo azetidines as anti-microbial, anti-convulsant, anti-inflammatory agents. Indian J chem.2002; 41B: 2357-2363.
5. Mc Kittrick BA, Ke Ma, Huie K, Yumibe N, Devis H, Clader JJW, Czarniecki M. Synthesis of C3 heteroatom-substituted azetidinones that display potent cholesterol absorption inhibitory activity. J med chem.1998; 41: 752-759.
6. Bhusare SR, Shinde AB, Pawar RP, Vibhute YP. Synthesis and anti-microbial activity of heterocyclic Schiff bases, 4-thiazolidinones and 2-azetidinones. Indian J Pharm Sci.2004; 228-231.
7. Patel HS, Patel VK. Synthesis of some new 4-(N,N'-dimethyl-amino-sulfonyl-phenyl)-3-chloro-4-phenyl azetidine-2-ones. Indian J heterocycl chem.2003; 12: 253-256.
8. Chowdary PVR, Jawarkar SG, Shashikala RK, Girija R, Prasad V. Synthesis and biological evaluation of 4-(substituted aryl)-1-N-indolyl-acetamido)-3-chloro-2-azetidinones. Indian J Pharm Sci.2005; 610-614.
9. Mehta PD, Sengar NPS, Subramanyam EVS, Satyanarayana D. Synthesis and biological activity studies of some thiazolidinones and azetidinones. Indian J Pharm Sci.2006; 68(1): 103-106.
10. Desai NC, Lopa SB, Vadekar KR, Kagathara NK. Synthesis and anti-bacterial activity of 4-oxo thiazolidines and 2-oxo azetidines. Indian J heterocycl chem.2001; 10: 193-196.
11. Dinesh SN, Shah AC. Synthesis of O-benzyl azetidinone derivative of (R) and (S)-2-amino butanols. Indian J heterocycl chem.2007; 16: 221-226.
12. Pratibha S, Kumar A, Sharma S. Bisheterocyclic synthesis and anti-microbial studies on some biologically significant 2-[N-(3'-chloro-4'-substituted azetidinone-2)]amino-4-hydroxy purines. Indian J chem.2004; 43B: 385-388.
13. Benito A, Perdo A, Nati RS, Alberto RV. Thermally induced isomerisation of cis-1,3,4-substituted-2-azetidinones. J org chem.2000; 65: 4453-4455.
14. Halve KA, Dubey R, Bhadauria D, Bhaskar B, Gour P. Synthesis of some new azetidine-2-ones as potential anti-microbial agents. J Indian chem Soc.2006; 83: 386-388.
15. Halve KA, Bhadauria D, Bhaskar B, Dubey R, Bhadauria R. Design, synthesis and in vitro studies of some biologically significant N-3-chloro-4-[2-hydroxy-5-(phenyl azo)phenyl]azetidine-2-ones. J Indian chem Soc.2007; 84: 193-196.
16. Chowdary BP, Mulwad VV. Synthesis and anti-microbial screening of N-[6-coumarinyl-amino-3-chloro-4-aryl]azetidine-2-one. Indian J heterocycl chem.2003; 12: 197-200.
17. Havaldar FH, Bhise SS, Burudkar SM. Convenient synthesis and biological activity of 2-azetidinones and 4-thiazolidinones. Indian J heterocycl chem.2005; 14: 297-300.
18. Bhat KI, Mubeen M, Kalluraya B. Synthesis and pharmacological activity of some azetidinones bearing Ibuprofen moiety. Indian J heterocycl chem.2003; 13: 183-184.
19. Modha JJ, Parmar JM, Datta NJ, Parekh HH. Synthesis and biological evaluation of some new azetidinones and thiazolidinones. Indian J chem.2002; 41B: 2694-2697.
20. Reddy PSN, Reddy PP, Vasanta T. Bisaza heterocycles:Part-7- Synthesis of novel Bisquinazolinyl β-lactams. Indian J chem.2002; 41B: 1946-1949.
21. Joshi HS, Kachhadia VV. Synthesis of 4-thiazolidinones and 2-azetidinones bearing benzo(b)thiophene nucleus possessing anti-tubercular and anti-microbial agents. Indian J chem.2003; 1544-1547.
22. Sharma SD, Bhaduri S. Synthesis of 2-azetidinones and other heterocycles from N-(3-hydroxy propyl)imines. Indian J heterocycl chem.2002; 11: 221-224.
23. Mehta DS, Shah VH. Synthesis and biological activity of 2-azetidinones, 4-thiazolidinones, 5-imidazolinones having benzthiazole moiety. Indian J heterocycl chem.2001; 11: 139-144.
24. Desai KG, Desai KR. Rapid and efficient synthesis of some biologically active 2-azetidinone under microwave irradiation. Indian J chem.2005; 44B: 2093-2096.
25. Mulwad VV, Shirodkar JM. Synthesis and biological activity of some new Schiff bases, thiazolidinones and azetidinones of 4-hydroxy coumarin. Indian J heterocycl chem.2002; 2: 199-202.
26. Bari SS, Madhan S, Sethi MK. Chemo enzymatic synthesis of chiral 3-hydroxy-azetidine-2-ones. J Indian chem. Soc.1999; 38B: 10-17.
27. Pelczar MJ, Chan ECS, Noel RK. Microbiology. 5th edition. New Delhi; tata Mcgraw Hill publishing company limited; 536-537.
9.0 / SIGNATURE OF THE CANDIDATE
10.0 / REMARKS OF THE GUIDE
11.0 / NAME AND DESIGNATION OF:
11.1 GUIDE / Prof.M.NARAYANA BABU.
Dept. of Pharmaceutical Chemistry,
M.S. Ramaiah College of Pharmacy,
Bangalore – 560 054
11.2 SIGNATURE
11.3 CO-GUIDE / NIL
11.4 SIGNATURE / NIL
11.5 HEAD OF THE DEPARTMENT
( INCHARGE ) / Prof. C.H.S. VENKATARAMANA
Dept. of Pharmaceutical Chemistry,
M.S. Ramaiah College of Pharmacy,
Bangalore – 560 054
11.6 SIGNATURE
12.0 / 12.1 REMARKS OF THE PRINCIPAL
12.2 SIGNATURE
13