ANTIMICROBIAL ACTIVITY OF AZETIDINONE DERIVATIVES: A REVIEW OF THE LITERATURE

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 2^nd 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.

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