Antimicrobial activity of novel c2-substituted 1,4-dihydropyridine analogues.

The antimicrobial activity of 3-methyl-5-isopropyl (or ethyl) 6-methyl-4-nitrophenyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives was evaluated. Prokaryotes (bacteria) appeared to be more sensitive to their antimicrobial activity than were eukaryotes (filamentous fungi). The best antibacterial activity was shown by derivative 33, which was able to inhibit the growth of Mycobacterium smegmatis (MIC33 = 9 µg.ml(-1)), Staphylococcus aureus (MIC33 = 25 µg.ml(-1)), and Escherichia coli (MIC33 = 100 µg.ml(-1)). In addition, derivative 4 demonstrated its antibacterial power on the acid-fast bacterial species M. smegmatis and on Gram-positive S. aureus. Focusing on the structure-activity relationship, it appears that the increase in the substituent bulk at the C2 position improved the antibacterial activity of the set of compounds studied. Derivatives 33 and 4, carrying 2-cyano-3-oxo-3-phenylprop-1-en-1-yl and allyliminomethyl groups, respectively, showed significantly higher inhibition activities on all tested microorganisms in comparison with the rest of the derivatives. This enhancement was also in good correlation with different log P values (lipophilicity parameter).

Novel quercetin derivatives in treatment of peroxynitrite-oxidized SERCA1.

Sarco/endoplasmic reticulum calcium ATP-ase (SERCA) is regulated by low concentrations of peroxynitrite and inhibited by high levels, as indicated in human diseases. We studied quercetin (Q) and its novel derivatives monochloropivaloylquercetin (MPQ) and chloronaphthoquinonequercetin (CHQ) as agents with expected preventive properties against peroxynitrite-induced SERCA impairment. Q and MPQ protected the SERCA1 against peroxynitrite induced activity decrease, while CHQ potentiated the inhibitory effect of peroxynitrite. Quercetin derivatives were found to be weaker antioxidants compared with Q, as indicated by their ability to scavenge peroxynitrite and prevent of SERCA1 carbonylation, both decreasing in the order (Q > MPQ > CHQ). Quantum-chemical values of theoretical parameter E HOMO also indicated lower antioxidant capacities for MPQ and CHQ. Prooxidant properties estimated by calculations of frontier molecular orbitals (E LUMO) correlated with experimentally determined SH-group decrease induced by the compounds studied. Both methods showed a decrease of prooxidant properties as follows: CHQ > MPQ > Q. In addition, experimentally measured half-wave potentials indicated stronger prooxidant properties of quercetin derivatives as compared to Q. More expressive alterations of conformation in the transmembrane region of SERCA1 induced by quercetin derivatives, as compared with Q, may at least partially correlate with their higher lipophilicities. The protective effects of Q and MPQ on different isoforms of SERCA activity may be useful in prevention and treatment of inflammation or muscle diseases. The inhibitory effect of CHQ on SERCA isoforms may be beneficial in therapeutic approaches aimed at anti-tumor treatment.

Induction of resistance in Mycobacterium smegmatis.

In this work, we assayed the ability of newly prepared indolizine derivates (epimers) 6C and 6A to inhibit the growth of Mycobacterium smegmatis and used them for resistance induction. 6A inhibited the growth of M. smegmatis at a concentration of 100 µg/mL. No inhibitory effect was observed in the presence of 6C. By incubating the bacteria with 6C and 6A, colonies resistant to 6A were observed. Finally, 37 stable resistant strains were isolated. These resistant strains were able to grow on a 5-fold higher concentration of 6A (500 µg/mL) than the minimal inhibitory concentration of the wild type (100 µg/mL), with no growth inhibition. Resistant strains were then tested for cross-resistance to other antibiotics: ampicillin, tetracycline, ciprofloxacin, chloramphenicol, gentamicin, and streptomycin. Determinations of resistance patterns to 6 antibiotics revealed 36 strains that were resistant to at least one drug.

Voltammetric determination of caffeine in beverage samples on bare boron-doped diamond electrode.

A sensitive and selective electrochemical method for the caffeine determination using bare boron-doped diamond electrode was developed. It was found that caffeine provided highly reproducible and well-defined irreversible oxidation peak at very positive potential. The effects of supporting electrolyte, pH and scan rate on the voltammetric response of caffeine oxidation were studied to select the optimum experimental conditions. Linear response of peak current on the concentration in the range from 4×10(-7) to 2.5×10(-5)M, good repeatability (RSD of 2.1%) and detection limit of 1.5×10(-7)M without any chemical modifications and electrochemical surface pretreatment were evaluated. The effect of possible interferents appeared to be negligible which evidently proved very good selectivity. The proposed method was successfully applied for the caffeine determination in commercially available beverage samples, with results in a close statistical agreement to those declared by manufacturer and HPLC used as independent method.