Microwave-assisted synthesis of some hybrid molecules containing penicillanic acid or cephalosporanic acid moieties and investigation of their biological activities

Serap Basoglu,Sengul Alpay-Karaoglu,Serdar Ulker,Neslihan Demirbas

doi:10.1007/s00044-013-0898-4

Serap Basoglu, Sengul Alpay-Karaoglu + Show 2 more

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https://doi.org/10.1007/s00044-013-0898-4

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Abstract

Ethyl 4-amino-2-fluorophenylpiperazin-1-carboxylates containing a 1,3-oxazol(idin)e, 5-thioxo-1,2,4-triazole, 1,3,4-thiadiazole, 5-thioxo-1,3,4-oxadiazole, or 1,3-thiazole nucleus were obtained starting from ethyl piperazine-1-carboxylate (1) by several steps. The treatment of amine, 3 or hydrazide, 9 with several aromatic aldehydes generated the corresponding arylmethyleneamino (3a–f) or arylidenehydrazino (12a–c) compounds. The Mannich reaction between the 1,2,4-triazole or 1,3,4-oxadiazole compounds and 7-aca produced cephalosporanic acid derivatives. Penicillanic acid derivatives were obtained when 6-apa was used in the Mannich reactions. The synthesized compounds were screened for their antimicrobial, antilipase, and antiurease activities. Some of them were found to possess good-moderate antimicrobial activity against the test microorganisms. Two compounds exhibited antiurease activity, and four of them displayed antilipase activity.

Highlights

The limitations of the existing antibacterial drugs caused by various reasons including drug resistance, the serious side effects, and/or lack of efficacy made infectious diseases a vicious cycle
Synthesis of the intermediate and target compounds was performed according to the reactions outlined in Schemes 1, 2, and 3
Ethyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylate (3), that was obtained starting from compound 1 by two steps, was converted to the corresponding arylmethylenamino derivatives (4a–f) by the treatment with several aromatic aldehydes

Summary

Introduction

The limitations of the existing antibacterial drugs caused by various reasons including drug resistance, the serious side effects, and/or lack of efficacy made infectious diseases a vicious cycle. The rising prevalence of multi-drug resistant bacteria continues to serve medicinal chemists to search and discove novel antimicrobial agents effective against pathogenic microorganisms resistant to current treatment. Among the strategies addressed to the synthesis of compounds possessing antimicrobial activity, the syntheses of hybrid molecules incorporating different heterocyclic moieties have been attracting widespread attention (Mallikarjuna et al, 2009). A number of N-containing heterocyclic compounds constitute important building blocks in organic and medicinal chemistry. Triazoles have been shown to possess a number of desirable activities in the context of medicinal chemistry. Ribavirin (antiviral), rizatriptan (antimigraine), alprazolam (psychotropic), fluconazole, and itraconazole (antifungal) are the best examples for potent drugs possessing triazole nucleus (Holla et al, 2006; Walczak et al, 2004; Jones et al, 1965; Ashok et al, 2007). Tazobactam, a b-lactamase inhibitor is the other best known example of triazole containing structures with the broad spectrum antibiotic piperacillin (Kategaonkar et al, 2010)

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