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ANTIMICROBIAL ACTIVITY OF AZETIDINONE DERIVATIVES: A REVIEW OF THE LITERATURE

 

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About Author:
Alex Martin*
Department of Pharmaceutical Chemistry,
St. Joseph’s College of Pharmacy, Kerala University of Health Sciences,
Cherthala-688524 (Kerala), India.
aalexmartin@rediffmail.com

Abstract
Azetidinone is the simplest β-lactam known for a number of pharmacological activities. Azetidinones exhibits a wide range of biological activities which includes anti-tubercular, anti-inflammatory, anti-tumor anti-HIV, anti-parkinsonian, anti-diabetic activities etc. In addition, the azetidinone moiety is reposted as a potent mechanism based inhibitor of several enzymes like human tryptase, chymase, thrombin, leukocyte elastase, human cytomegalovirus protease and serine protease enzyme. The four membered heterocyclic β-lactam is well known for its antibacterial and antifungal activities. They have shown significant antibacterial activity against a wide range of microorganisms like fungi, Gram positive strains such as Staphylococcus aureus, Bacillus subtilis and Bacillus lintus and Gram negative strains such as Escheria coli, Vibrio cholera and Pseudomonas aeruginosa. The present review reports the methods of synthesizing some of the 1,3,4-oxadiazole derivatives and their anti-microbial activity.

Reference Id: PHARMATUTOR-ART-1985

INTRODUCTION
A β-lactam ring, is a four-membered lactam. It is named as such, because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl group. The simplest β-lactam possible is 2-azetidinone.


2-Azetidinones shows various biological activities such as antifungal, antibacterial, antitubercular, anticonvulsant, analgesic, anti- inflammatory, antiviral activities. It is also known as a potent mechanism based inhibitor of several enzymes like human tryptase, chymase, thrombin, leukocyte elastase, human cytomegalovirus protease and serine protease enzyme. The four membered heterocyclic β-lactam is well known for its antibacterial and antifungal activities. This review article highlights the recent work that has been carried out on azetidinones reporting the antimicrobial properties of 2-azetidinones.

J. Senthil Kumaran et al 1 synthesized transition metal complexes from Schiff bases derived from 4-aminoantipyrine and 4-hydroxy-3-methoxy benzaldehyde.


Sathe Bushankumar S. et al 2synthesized and screened various derivatives of flourobenzothiazole incorporated azetidinones. The titled compounds exhibited significant antimicrobial, anthelmintic and anti-inflammatory activity.

V. Harinadha Babu et al 3(synthesized a new series of azetidin-2-ones from isoniazid. The synthesized compounds have shown promising anti-bacterial activity.

Amit M. Patel and Tarun M. Patel et al 4 synthesized a new series of azetidinone derivatives from 4-(1H-napthol(1,8-de)(1,2,3) triazin-1-ylsulfonyl)aniline. The newly synthesized compounds showed moderate to good antibacterial and antifungal activities.

Ravindra kumar, Abha Shukha and D.S. Tyagi et al 5synthesized a new series of bioactive azetidinones and were found to have good activity against all bacterial strains used.

Akash R. Patel and Jabali J. Vora et al 6synthesized Schiff bases from 4-amino antipyrine and 1,3-diphenyl-1H-pyrazole-4-carbaldehyde. Some of the derivatives showed promising antibacterial and antifungal activity.

Anand P. Mishra and Rajendra Jain et al 7synthesized the metal complexes of Schiff bases of 4-amino antipyrine and 2-pyridine caboxaldehyde. The Schiff bases formed were found to have good antibacterial activity.

Pushkal Samadhiya et al 8synthesized a new series of 2-azetidinone derivatives from phenothiazine. The synthesized derivatives showed varying range of antibacterial, antifungal and antitubercular activity depending on the substituents.

Chavi Raj Singh et al 9synthesized a series of azetidinone derivatives from 2-amino-5-(benzothiazol-2’-yl-thiomethyl)-1,3,4-thiadiazole. It appeared from the screening results that most of the synthesized compounds inhibited the mycelia growth of test fungi at 1000ppm.

Subash B. Junne et al 10synthesized some new Schiff bases and 2-azetidinones from iodo hydroxyl biphenyl moiety. Some of the synthesized compounds showed potential antibacterial activity.

A.R. Sundane and Prabhakar Walmik et al 11synthesized azetidinone derivatives linked to indole nucleus. The compounds were screened for their antioxidant, antimicrobial, antimycobacterial and cytotoxic activities. Some of them displayed excellent activity.

Jyotsana S. Meshram et al 12 synthesized a novel series of azetidinones from 1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one under microwave methods. The compounds showed potent antibacterial activity.

Chetan P. Pulate et al 13synthesized novel azetidinone derivatives from dehydroacetic acid by using microwave system. The compounds showed moderate to good antimicrobial activity against some bacteria and fungi.

B.A. Baviskar et al 14synthesized thiazolyltriazole substituted azetidinone derivatives. The new analogues, among which five of them showed maximum antibacterial activity and others showed moderate to good activity.

Jainey P. James et al 15synthesized a novel series of azetidinone derivatives from sulphamethoxazole moiety. The resultant compounds showed moderate to good antimicrobial activity against some bacteria and fungi.

Rahul B. Shete et al 16synthesized novel azetidinone derivatives of pyrazolone. The products showed moderate to good antibacterial activity.

V. Prakash and M.S. Suresh et al 17prepared chelates of Schiff base derived from 4-aminoantipyrine, furfural and o-phenylenediamine. The MIC values showed that the intermediate Schiff bases also exhibited antibacterial activity.

Amit Rai et al 18also synthesized and characterized Schiff base ligands derived from 4-amino antipyrine and 4-aminosalicylaldehyde, benzene-1,2-diamine and its metal complexes.

Kokila Parmer, Rinku Patel and Sarju Prajapati et al 19synthesized new azetidinone derivatives from aryl amino-1,3,4-oxadiazole. The new derivatives were screened for their antibacterial and antifungal activity and were found to have promising activities.

Ajay Bhagerwal et al 20synthesized azetidinone derivatives from napthylamine moiety. The synthesized compounds exhibited good antibacterial and antifungal activities.

Jyotsna Meshram et al 21synthesized 3-phenyl-4-substituted phenylazetidin-2-ones from 2-aminothiazoles. The antibacterial screening data shows that the compounds are active against the used strains.

A. Rajasekharan et al 22synthesized a series of seven novel azetidinones by cyclocondensation of various Schiff bases of phenothiazine with chloroacetyl chloride in the presence of triethylamine. The titled compounds were found to have antitubercular, antibacterial, antifungal and anti-inflammatory activities.

Rajiv Dua and S.K. Sonwane et al 23synthesized some new 2-azetidinone derivatives of 2-methylbenzimidazole. The derived compounds were screened for their antimicrobial activity whose results showed that some of them displayed pronounced biological activity.

Yeshwant B. Vibhute et al 24synthesized novel Schiff bases of 4,4’-sulfonyldianiline by using microwave assisted synthesis. The results of the antibacterial activity indicated that the synthesized compounds had moderate to potent activities at low and high concentrations with reference to their appropriate reference standards.

Jyotsna Meshram, Parvez Ali and Vandana Tiwari et al 25synthesized a series of 3-chloro-1[(2-hydroxynapthalen-1-yl-substituted phenylmethyl)]-4-substituted phenylazetidin-2-ones under microwave irradiation. The synthesized compounds were screened for their antibacterial activity and were found to be promising candidates as new antibacterial agents.

Bhupendra Mistry and Smitha Jahuari et al 26synthesized and characterized some quinoline based azetidinones. The results of antimicrobial studies and bioassays showed that the newly synthesized analogues emerged as lead molecules with excellent MIC.

N. Anbalagan et al 27synthesized 2-(4-(azetidin-2-one)-3-chloro-4-phenyl)-1H-phenyl benzimidazole. The synthesized compounds showed significant activity of antibacterial, antifungal, analgesic and anti-inflammatory comparable to that of a standard.

S. Jubie et al 28synthesized different derivatives of 2-azetidinones from p-anisidine and different aldehydes. All the derivatives showed comparable antimicrobial activities. Among these, the one having 2,4-dimethylaminophenyl at 2nd position have shown good activity in all species.

Marunmayee P. Toraskar et al 29synthesized novel N-substituted-2-azetidinone derivatives using Schiff bases synthesized from ethyl-1H-benzotriazole-1-acetate. The synthesized compounds exhibited moderate to good antifungal activity when tested in-vitro against C. albicans.

S.J. Wadher et al 30synthesized a series of Schiff bases and 2-azetidinones of 4,4’-diaminodiphenylsulphone. The compounds were characterized and some derivatives were found to exhibit potent antibacterial activity.

REFERENCES:
1.Senthil Kumaran J., Priya S., Jayachandramani S. and Mahalakshmi S. (2013). Synthesis, Spectroscopic Characterization and Biological activities of Transition Metal Complexes derived from Tridentate Schiff base. Journal of Chemistry, 32, 67-78.
2.Bushankumar S.S. and Saneer S.S. (2012). Synthesis and biological screening of various different derivatives of Flourobenzothiazole incorporated Azetidinones. Journal of Pharmaceutical and Scientific innovation, 13, 32-45.
3.Babu H.V., Rani S.E., Parmeshwar R., Ranganath S.Y., Naveen B.K. and Kumar A.G. (2012). Synthesis and antibacterial screening of some novel N-(3-chloro-2-oxosubstituted phenyl azetidin-1-yl) isonicotinamide and 4-(5-substituted phenyl-1,3,4-oxadiazol-2-yl)pyridine derivatives. International Journal of Pharmacy and Pharmaceutical Sciences, 4, 23-34.
4.Patel A.M. and Tarun M.P. (2012). Synthesis and Anti-microbial activity of some new Azetidinone derivatives. Der Pharmacia Lettre, 4, 579-583.
5.Kumar R., Shukla A. and Tyagi T.S. (2012). An efficient synthesis of Bioactive Azetidinones and Thiazolidinones of 3-methyl-1-phenyl-1H-pyrazol-5-ol.International Journal Of Scientific and Research Publications, 2, 47-59.
6.R.P. Akash, Jabali J.V., Dinesh R.P. and Sandip D. (2012). Synthesis and Antimicrobial activity of some new 4-(substituted aryl)-1,3-diphenyl-1H-pyrazole-4-ylmethyleneamino)-1,5-dimethyl-2-phenylpyrazolidin-3-one derivatives, International Journal of Pharmaceutical Science Research, 3, 68-79.
7.Mishra A.M., Rudra M., Rajendra J. and Santosh G. (2012). Synthesis of new Cobalt, Nickel and Copper complexes with Isatin-3-chloro-4-flouroaniline and 2-pyridinecarboxylidiene-4-aminoantipyrine and their Anti-microbial studies. Journal of Microbiology, 40, 20-26.
8.Pushkal S., Ritusharma S., Srivastava S.D. and Srivastava S.K. (2012). Synthesis and Pharmaceutical importance of 2-azetidinone derivatives of phenothiazine. Journal of Chemical Science, 124, 633-637.
9.Singh C.R. and Singhal A. (2012). Synthesis of novel Schiff base and azetidinone derivatives and their Anti-microbial activity. European Journal of Chemistry, 34, 272-276.
10.Junne S.B., Archana B.K., Sainath B.Z., Saheb L.S. and Yeshwant B.V. (2012). Synthesis and Antibacterial activity of some new Schiff bases and 2-Azetidinones containing iodohydroxybiphenyl moiety. International Multidisciplinary Research Journal, 2, 44-47.
11.Sundane A.R. and Walmik P. (2012). Synthesis, Antioxidant, Anti-microbial, Anti-microbial, Anti-mycobacterial and Cytotoxic activities of Azetidinone and Thiazolidinone moieties linked to Indole nucleus. Journal of Chemistry, 28, 49-56.
12.Meshram S.J. , Himani N.C., Ramakanth P. and Venkateshwar J. (2012). An efficient synthesis of novel bioactive Azetidinones and Thiazolidinones of 1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one. International Journal of Pharma and Bio Sciences, 2, 24-32.
13.Pulate C.C., Swamy G., Rishikesh V. and Goli D. (2011). Microwave assisted synthesis and Antimicrobial activity of novel Azetidinone from Dehydroacetic acid. International Journal of Drug Discovery and Design, 2, 483-487.
14.Baviskar B.A., Shiradhkar M.R., Khadabadi S.S., Deore S.L. and Bothara K.G. (2011). Synthesis of thiazolyltriazole substituted azetidinones as antimicrobial agents. Indian Journal of Chemistry, 50B, 321-325.
15.James P.J., Ishwar B.K., Sunil K.M., Shastry C.S. (2011). Antimicrobial studies of azetidinone derivatives from sulphamethoxazole moiety. Journal of Chemical and Pharmaceutical Research, 6, 234-243.
16.Shete B.R., Rishikesh V.A., Rajesh J.O., Sandip S.K., Sampada S.J. and Hemlata M.N. (2011). New 4-(substituted)-pyrazolone, Part 1 : Microwave assisted synthesis and antibacterial activity of novel 4-substituted azetidinone derivatives of pyrazolone. International Journal of Drug Design and Discovery, 2, 648-653.
17.Prakash V. and Suresh M.S. (2011). Preparation, Characterization and Antibacterial studies of Chelates of Schiff base derived from 4-aminoantipyrine, furfural and o-phenylenediamine. E-Journal of Chemistry, 28, 1408-1416.
18.Rai A., Ashish K.R. and Sirohi R. (2011). Synthesis and Characterization of Schiff base ligands derived from 4-aminoantipyrine and 4-nitrosalicylaldehyde, Benzene-1,2-diamine and its complex with Molybedenum Tricarbonyl. VSRD Technical and Non-Technical Journal, 8, 352-357.
19.Parmar K., Modi V., Prajapati S. and Patel R. (2011). A Facile and Expeditious approach for the synthesis of 2-azetidinone derivatives with antimicrobial activity. Asian Journal of Biochemical and Pharmaceutical Research, 1, 36-47.
20.Bhagerwal A., Ashish B., Rakesh K. and Dinesh K.P. (2011). Synthesis and Antimicrobial studies of Azetidinone derivatives from Napthylamine Moiety. International Journal of Chem Tech Research, 3, 274-279.
21.Meshram J., Parvez A. and Vandana T. (2010). Microwave mediated cyclocondensation of 2-aminothiazole into β-lactam derivatives: Virtual Screening and In-vitro Antimicrobial activity with various microorganisms. International Journal of Chem Tech Research, 2, 956-964.
22.Rajasekharan A., Periasamy M. and Venkatesan S. (2010). Synthesis, Characterization and Biological activity of some novel azetidinones . Journal of Developmental Biology and Tissue Engineering, 2, 5-13.
23.Dua R., Sonwane S.K., Srivastava S.K. and Srivastava S.D. (2010). Synthesis of some novel 2-azetidinone derivatives of 2-methylbenzimidazole by conventional and microwave assisted synthesis and evaluation of their antimicrobial efficacy. Der Pharmacia Lettre, 2, 483-487.
24.Vibhute B.Y., Omprakash G., Bhanusree S., Sainath B.Z. and Shivaji B.C. (2010). Comparative study of Conventional and Microwave assisted synthesis of novel Schiff bases and their antimicrobial screening. Journal of Chemical and Pharmaceutical Research, 6, 234-243.
25.Meshram J., Vandana T. and Pervez A. (2010). Synthesis and Antibacterial activity of 3-chloro-1-[(2-hydroxynapthalen-1-yl-(substituted)-phenylazetidin-2-ones and Thiazolidin-4-ones encompassing Benzthiazole. Indian Journal of Pharmaceutical Science, 12, 34- 42.
26.Mistry B. and Jauhari S. (2010). Synthesis and Characterization of some quinoline based azetidinones and thiazolidinones as antimicrobial agents. Archives of Applied Science Research, 6, 332-343.
27.Anbalagan N., Shanmugapandiyan P., Denshing K.S., Illavarasan R. and Nirmal R. (2010). Synthesis and biological activity of 2-[(thiazolidin-4-one) phenyl]-1H-phenylbenzimidazoles and 2-[4-(azetidin-2-one)-3-chloro-4-phenyl]-1H-phenylbenzimidazoles. International Journal of Pharmaceutical Sciences and Drug Research, 2, 115-119.
28.Jubie S., Gowramma B., Nitin K., Kalirajan R., Gomathi S. and Elango K. (2009), International Journal of Chem Tech Research, 1, 153-157.
29.Toraskar M.P., Vilasrao M., Kadam P., Vithal D. and Kulkarni M. (2009). Synthesis and antifungal activity of some Azetidinones. International Journal of Chem Tech Research, 1, 1194-1199.
30.Wadher S.J., Pauranik M.P., Karanke N.A. and Yeole P.G. (2009). Synthesis and Biological evaluation of Schiff base of Dapsone and their derivatives as Antimicrobial agents.International Journal of Pharma Tech Research, 1, 22-33.

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