Synthesis and in-vitro antibacterial activity of/N-piperazinyl quinlone derivatives with 5-chloro-2-thienyl group

Fluoroquinolones are an important group of antimicrobial agents that are used widely in the treatment of various infectious diseases. The purpose of the present study was to synthesize new N-piperazinyl quinolone derivatives with 5-chloro-2-theinyl group having possible antimicrobial activity. Reaction of ciprofloxacin [1], norfloxacin [2] and enoxacin [3] with alpha-bromoketone 10 or alpha-bromooxime derivatives 11a-c in DMF, in the presence of NaHCO[3] at room temperature, afforded corresponding ketones 4a-c or oxime derivatives 5-7[a-c], respectively. The synthesized compounds were tested against a series of Gram-positive and Gram-negative bacteria. The results of MIC tests against both Gram-positive and Gram-negative bacteria revealed that ciprofloxacin derivatives [compounds 4a, 5a, 6a and 7a] were more active than norfloxacin and enoxacin analogues. Compound 5a, containing N-[2-[5-chlorothiophen-2-yl]-2-hydroxyiminoethyl] residue provided a high in vitro antibacterial activity against Gram-positive bacteria, with MIC of 0.06, 0.125, 0.5 and 0.125 micro g/mL against S. aureus, S. epidermidis, E. feacalis and B. subtilis, respectively. Its activity was found to be 4 to 8 times better than reference drug [ciprofloxacin] against all Gram-positive bacteria with the exception of E. feacalis

In-vitro susceptibility of Pseudomonas pseudomallei isolated in Malaysia to some new cephalosporins and a quinolone.

The current drugs recommended for treatment of melioidosis are tetracycline, chloramphenicol and cotrimoxazole. Unfortunately these drugs are not the drug of choice in an acutely ill patient with septicaemia prior to the availability of laboratory results. With the discovery of the new cephalosporins which have a broad spectrum of activity clinicians are using them either alone or in combination with other antibiotics in such critical situations. Hence, an in-vitro study was carried out on the susceptibility of 41 strains of P. pseudomallei isolated in Malaysia, to these new cephalosporins and a new quinolone. The results showed that all the cephalosporins tested had some activity on the strains tested, with ceftazidime being the most active drug. Pefloxacin had very poor activity. However, further clinical studies are required to determine the duration, dosage and in-vivo activity of the antibiotics.