Antibiotic resistance and drug modification: Synthesis, characterization and bioactivity of newly modified potent ciprofloxacin derivatives.

Development of new derivatives of commercial antibiotics using different organic reagents and testing these derivatives against different microorganisms are the main goals of this article. Thus, the antibiotic ciprofloxacin, CF, was acylated via reaction with ethyl cyanoacetate and ethyl acetoacetate in basic medium to give the cyanoacetylpiprazinyl dihydroquinoline derivative 3, and oxobutanoylpiprazinyl dihydroquinoline derivative 5, respectively. On the other hand, N-alkylated derivatives 8-10, were prepared through the reaction of CF with chloroacetonitrile, chloroacetyl acetone and chloroacetone in the presence of carbonate salt. In basic medium, both 3 and 10 were coupled with benzenediazonium chloride to afford hydrazono derivatives, which were then cyclized to give 4-(dihydropyridazinecarbonyl)piperazinyl-1,4-dihydroquinoline. Furthermore, compounds 3 and 10 were reacted with benylidenemalononitrile to produce 4H-pyan and pyrido[1,2-a]pyrazine derivatives, respectively. Both 3 and 10 were reacted with DMFDMA to give enaminone derivatives. These enaminones were cyclized to aminopyrimidine derivatives by reacting with urea or thiourea. X-ray, elemental analysis and spectral data were used to illustrate and confirm the structures of the isolated compounds. The bioactivities of the novel compounds were investigated against different gram-positive and gram-negative bacteria. In addition, these novel antibiotic derivatives were tested against ciprofloxacin-resistant bacteria isolated from patients aged 65-74 years. This study reveals that most of the modified drugs show high to moderate antibacterial activity. Additionally, these drugs show good effects against ciprofloxacin-resistant bacteria.

Effect of sulfa drugs on kidney function and renal scintigraphy.

AIM: The sulfonamide group is widely used for bacterial diseases including kidney and urinary tract infections. The present study investigates the effect of a sulfa drug on kidney function and renography studies by using a radionuclide. METHODS: Renography studies were performed on New Zealand white rabbits. Each rabbit was injected with 48.1 MBq technetium-99m mercaptoacetyltriglycine ((99m) Tc-MAG-3). Dynamic images were acquired using a gamma camera. Radioactivity time curves were generated from the regions of interest, time to peak activity (Tmax ) and time from peak to 50% activity (T1/2 ). Each rabbit served as its own control. The sulfa drug was given to these rabbits for 7 days (i.v injection 130 mg/kg daily in two divided doses; i.e. the single dose is 65 mg/kg), then dynamic images were acquired. RESULTS: Treatment with sulfa shifted the experimental curves to the right of the control curves. This result showed that there was a delayed renal uptake of (99m) Tc-MAG-3 and its clearance. Calculated averages of Tmax were 2.2 ± 0.3 and 5.9 ± 0.5 min; while for T1/2 were 3.1 ± 0.3 and 8.4 ± 0.6 min for control and sulfa-treated rabbits, respectively (n = 20; P < 0.05). CONCLUSION: Our results indicate that sulfa drug induced pharmacokinetic changes because of delaying both the Tmax and T1/2 . Sulfa drug has an effect on the reabsorption from the renal tubules and the excretion process of (99m) Tc-MAG-3 which is excreted almost exclusively by the renal tubules. Therefore, sulfa drug causes a deterioration in kidney function and an alteration on radionuclide renography.

Verapamil induces calcium influx in the trachea.

Verapamil, a Ca(2+) entry blocker, can induce bronchorelaxation and bronchoconstriction. The mechanism of verapamil-induced bronchoconstriction is poorly understood. The present study determines the direct effect of verapamil on smooth muscle of isolated ovine airways and analyzes the mechanisms involved. Isolated tracheal strips were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to verapamil as assessed by basal tone were examined in the presence or absence of epithelium. The effects of verapamil on carbachol and cooling-induced contraction were also recorded. Measurement of unidirectional fluxes was carried out using (45)Ca(2+) in the absence or presence of verapamil. Verapamil induced contractions of basal tracheal smooth muscle that were proportional to its concentrations. Removal of epithelium did not affect the verapamil contractile effect. Verapamil-induced contractions were abolished in Ca(2+)-free Krebs solution containing 2 mM EGTA. Verapamil increased the (45)Ca(2+) influx into the tracheal smooth muscle. It caused relaxation of the muscle tone induced by carbachol or KCl, but it potentiated the effect of cooling-induced contraction. Verapamil induced Ca(2+) influx that may lead to bronchoconstriction. These results proved that verapamil may worsen bronchoconstriction; therefore verapamil should be used with caution in asthmatic individuals.