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IJEB Vol.45(12) [December 2007] >

Title: Antibacterial and toxicological evaluation of ß-lactams synthesized by immobilized ß-lactamase-free penicillin amidase produced by Alcaligenes sp.
Authors: Gayen, Jiaur R
Majee, Sutapa B
Das, Shuvendu
Samanta, Timir B
Keywords: Alcaligenes sp.
Penicillin amidase
Synthetic ß-Lactams
Toxicological evaluation
Issue Date: Dec-2007
Publisher: CSIR
Abstract: Search for anti-ß-lactamase and synthesis of newer penicillin were suggested to overcome resistance to penicillin in chemotherapy. It was found that clavulanic acid, an ant-ß-lactamase was ineffective due to its structural modification by bacteria. Thus, there is a need for the synthesis of newer pencillins. Retro-synthesis was inspired by the success of forward reaction i.e.conversion of penicillin G to 6-aminopenicillanic acid (6-APA) by biological process. In the present study a better enzymatic method of synthesis of newer pencillin by a ß-lactamase-free penicillin amidase produced by Alcaligenes sp. is attempted. Antibacterial and toxicological evaluation of the enzymatically synthesized ß-lactams are reported. Condensation of 6-APA with acyl donor was found to be effective when the reaction is run in dimethyl formamide (DMF 50% v/v) in acetate buffer (25 mM pH 5.0) at 37°C. Periplasm entrapped in calcium alginate exihibited the highest yield (~34%) in synthesis. The minimum inhibitory concentration of the synthetic products against Staphylococcus aureus and Salmonella typhi varied between 20–80 µg/ml. Some of the products exhibited antibacterial activity against enteric pathogens. It was interesting to note that product A was potent like penicillin G. LD50 value of three products (product A, B and C) was more than 12mg/kg. Furthermore, these synthetic ß-lactams did not exihibit any adverse effect on house keeping enzymes viz., serum glutamate oxalacetate-trans-aminase, serum glutamate pyruvate -trans-aminase, acid phosphatase, alkaline phosphatase of the test animals. The hematological profile (RBC and WBC) of the test animals also remained unaffected.
Page(s): 1068-1072
ISSN: 0975-1009 (Online); 0019-5189 (Print)
Source:IJEB Vol.45(12) [December 2007]

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