Synthesis and biological evaluation of 2-mercapto-1,3-benzothiazole derivatives with potential antimicrobial activity.

The enhancement of bacterial resistance of pathogens to currently available antibiotics constitutes a serious public health threat. So, intensive efforts are underway worldwide to develop new antimicrobial agents. To identify compounds with a potent antimicrobial profile, we designed and synthesized low molecular weight 2-mercaptobenzothiazole derivatives 2a-2l and 3a-3l. Both series were screened for in-vitro antibacterial activity against the representative panel of Gram-positive and Gram-negative bacteria strains. The biological screening identified compounds 2e and 2l as the most active ones showing an interesting antibacterial activity with MIC values of 3.12 microg/mL against Staphylococcus aureus and 25 microg/mL against Escherichia coli, respectively. The replacement of the S-H by the S-Bn moiety resulted in considerable loss of the antibacterial action of the 3a-3l series. The antibiotic action of compounds 2e and 2l was also investigated by testing their activity against some clinical isolates with different antimicrobial resistance profile. Moreover, the involvement of the NorA efflux pump in the antibacterial activity of our molecules was evaluated. Finally, in this paper, we also describe the cytotoxic activity of the most interesting compounds by MTS assay against HeLa and MRC-5 cell lines.

In vitro synergic efficacy of the combination of Nystatin with the essential oils of Origanum vulgare and Pelargonium graveolens against some Candida species.

In this study we investigated a synergistic effect between the essential oils Origanum vulgare, Pelargonium graveolens and Melaleuca alternifolia and the antifungal compound Nystatin. Nystatin is considered a drug of choice in the treatment of fungal infections, but it can cause some considerable problems through its side effects, such as renal damage. Finding a new product that can reduce the Nystatin dose via combination is very important. Our findings showed an experimental occurrence of a synergistic interaction between two of these essential oils and Nystatin. The essential oil O. vulgare appeared to be the most effective, inhibiting all the Candida species evaluated in this study. Some combinations of Nystatin and P. graveolens essential oil did not have any synergistic interactions for some of the strains considered. Associations of Nystatin with M. alternifolia essential oil had only an additive effect.

The inhibition of Candida species by selected essential oils and their synergism with amphotericin B.

In this work we highlight a possible synergistic anti-Candida effect between Melaleuca alternifolia, Origanum vulgare and Pelargonium graveolens essential oils and the antifungal compound Amphotericin B. The antifungal activity was assessed using the agar dilution method in eleven Candida strains. The results obtained indicate the occurrence of a synergistic interaction between the essential oils under study and Amphotericin B. P. graveolens essential oil appeared to be the most effective, inhibiting all the Candida species evaluated by this study.

Antibacterial effect of some essential oils administered alone or in combination with Norfloxacin.

UNLABELLED: The objective of the present study was that of verifying a possible synergistic antibacterial effect between Pelargonium graveolens [Lis-Balchin, M., Deans, S.G., Hart, S., 1996. Bioactive Geranium oils from different commercial sources. J. Essential Oil Res. 8, 281-290.] essential oil (and its main components) and Norfloxacin antibiotic. As a first step growth inhibition by some types of essential oils was assessed in five microbial species. The antimicrobial effects of P. graveolens oil, as well as those of its components, were evaluated by means of the agar dilution method (ADM) against Bacillus cereus ATCC 11778, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 35218, Staphylococcus aureus ATCC 6538 and S. aureus ATCC 29213. The results obtained highlighted the occurrence of a pronounced synergism between P. graveolens essential oil and Norfloxacin against three of the five bacterial species under study with a FIC index in the 0.37-0.50 range. Such antibacterial effects were also shown to increase, although to a lesser extent, when Norfloxacin was given with the main components of P. graveolens essential oil. SIGNIFICANCE AND IMPACT OF THE STUDY: The combination of Norfloxacin with either P. graveolens essential oil, or with some of the main components of this latter, in the treatment of infections caused by some bacterial species is likely to reduce the minimum effective dose of Norfloxacin thus minimizing the side effects of the antibiotic.

Antimicrobial activity of saponins from Medicago sp.: structure-activity relationship.

The antimicrobial activity of saponins from Medicago sativa, M. arborea and M. arabica against a selection of medically important yeasts, Gram-positive and -negative bacteria was investigated. Structure-activity growth inhibitory effects of related prosapogenins and sapogenins are also described. Increasing antibiotic activity was observed going from the saponin extracts to the sapogenin samples, suggesting that the sugar moiety is not important for the antimicrobial efficacy. Activity was especially high against Gram-positive bacteria (Bacillus cereus, B. subtilis, Staphylococcus aureus and Enterococcus faecalis) with M. arabica being the species showing a broader spectrum of action. Discrete antifungal activity was also observed, mainly against Saccharomyces cerevisiae. The observed antimicrobial properties of M. sativa and M. arborea were related to the content of medicagenic acid, while hederagenin seems to contribute to the bioactivity of M. arabica total sapogenins.

Structural modifications and antimicrobial activity of N-cycloalkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles.

A series of N-cycloalkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles 5a-j, N-cycloalkyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles 8a-e, and N-alkyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles 8f-h, were synthesized and tested for in vitro antibacterial and antifungal activities against four gram-positive and five gram-negative bacteria (Bacillus subtilis 6633, Enterococcus faecalis 29212, Staphylococcus aureus 6538, Staphylococcus aureus 25923, Escherichia coli 25922, Acinetobacter calcoaceticus a1, A. calcoaceticus a2, Pseudomonas aeruginosa 27835, Klebsiella oxytoca 49131), four yeast-like fungi and one fungus (Candida tropicalis 750, C. albicans 14053, C. albicans 10231, Cryptococcus laurentii 18803, and Saccharomyces cerevisiae). Microdilution broth and agar dilution methods were used for antimicrobial tests. The findings obtained showed that some of the tested compounds 5 and 8 were effective against some of the bacterial strains used, whereas, only compounds 8b-g exhibited a moderate antifungal activity against the yeast strains evaluated.

Synthesis and antibacterial activity of pyridazino[4,3-b]indole-4-carboxylic acids carrying different substituents at N-2.

The synthesis and the in vitro evaluation of antibacterial activity of new pyridazino[4,3-b]indole-4-carboxylic acids 2-4, 6 against some selected representative of Gram-positive and Gram-negative bacteria are reported. The role of the lipophilicity in the modulation of the antibacterial activity of the tested compounds is discussed. All the synthesized compounds appear quite weak against Gram-positive bacteria, whereas have no significant activity against Gram-negative bacteria. Only derivative 2g possesses an interesting activity against Gram-positive bacteria.