Steroidal hydrazones as antimicrobial agents: biological evaluation and molecular docking studies.

Most of pharmaceutical agents display several or even many biological activities. It is obvious that testing even one compound for thousands of biological activities is a practically not reasonable task. Therefore, computer-aided prediction is the method of choice for the selection of the most promising bioassays for particular compounds. Using PASS Online software, we determined the probable antimicrobial activity of the 31 steroid derivatives. Experimental testing of the antimicrobial activity of the tested compounds by microdilution method confirmed the computational predictions. Furthermore, P. aeruginosa and C. albicans biofilm formation was investigated. Compound 11 showed a biofilm reduction by 42.26% at the MIC of the tested compound. The percentages are lower than ketoconazole, but very close to its activity.

Functionally substituted 2-aminothiazoles as antimicrobial agents: in vitro and in silico evaluation.

Nine new functionally substituted derivatives of 2-aminothiazole were evaluated for antimicrobial activity using microdilution method against the panel of eight bacterial and eight fungal strains. Evaluation of antibacterial activity revealed that compounds are potent antibacterial agents, more active than ampicillin and streptomycin except of some compounds against B. cereus and En. cloacae. The best compound appeared to be compound 8. The most sensitive bacteria appeared to be En. cloacae, while L. monocytogenes was the most resistant. Compounds also exhibited good antifungal activity much better than two reference drugs, ketoconazole and bifonazole. Compound 1 exhibited the best antifungal activity. The most sensitive fungus was T. viride, while A. fumigatus was the most resistant. Bacteria as well as fungi in general showed different sensitivity towards compounds tested. Molecular docking studies revealed that MurB inhibition is probably involved in the mechanism of antibacterial activity, while CYP51 of C. albicans is responsible for the mechanism of antifungal activity. Finally, it should be mentioned that all compounds displayed very good druglikeness scores.

Caffeic and 3-(3,4-dihydroxyphenyl)glyceric acid derivatives as antimicrobial agent: biological evaluation and molecular docking studies.

Herein we report the evaluation of the antimicrobial activity of some previously synthesized 3-(3,4-dihydroxyphenyl)glyceric acid in benzylated and in free 3,4 hydroxy groups in catechol moiety along with some caffeic and 3-(3,4-dihydroxyphenyl)glyceric acid amides using the microdilution method. The evaluation revealed that compounds showed in general moderate to low activity with MIC in range of 0.36-4.5 mg/mL. Compounds were also studied against three resistant bacteria strains MRSA (Methicillin-resistant Staphylococcus aureus), E. coli and P. aeruginosa. Seven out of ten compounds were more potent than reference drugs ampicillin and streptomycin against MRSA, while against another two resistant strains seven compounds showed low activity and the rest were inactive. Antifungal activity of the tested compounds was much better than antibacterial, with MIC in the range of 0.019-3.0 mg/mL. Compounds #7 and 15 showed good activity against all fungi tested, being more potent than ketoconazole and in some case even better than bifonazole used as reference drugs. Docking studies revealed that the most active compound #7 binds to the haem group of the enzyme in the same way as ketoconazole.

Appendix A. dithioloquinolinethiones as new potential multitargeted antibacterial and antifungal agents: Synthesis, biological evaluation and molecular docking studies.

Herein we report the design, synthesis, molecular docking study and evaluation of antimicrobial activity of ten new dithioloquinolinethiones. The structures of compounds were confirmed by 1H NMR, 13C NMR and HPLC-HRMS. Before evaluation of their possible antimicrobial activity prediction of toxicity was performed. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. All compounds appeared to be more active than ampicillin and almost all than streptomycin. The best antibacterial activity was observed for compound 8c 4,4,8-trimethyl-5-{[(4-phenyl-5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)thio]acetyl}-4,5-dihydro-1H-[1,2]dithiolo[3,4c]quino lone-1-thione). The most sensitive bacterium En.cloacae followed by S. aureus, while L.monocytogenes was the most resistant. All compounds were tested for antifungal activity also against eight fungal species. The best activity was expressed by compound 8d (5-[(4,5-Dihydro-1,3-thiazol-2-ylthio)acetyl]-4,4-dimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione). The most sensitive fungal was T. viride, while P. verrucosum var. cyclopium was the most resistant one. All compounds were more potent as antifungal agent than reference compound bifonazole and ketoconazole. The docking studies indicated a probable involvement of E. coli DNA GyrB inhibition in the anti-bacterial mechanism, while CYP51ca inhibition is probably responsible for antifungal activity of tested compounds. It is interesting to mention that docking results coincides with experimental.

Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections.

Aspergillosis represents a spectrum of fungal diseases which are caused by fungi of the genus Aspergillus. Animal models have been developed and used to address immune-based mechanisms of defense against these fungi. Invertebrate models enabled mass screening of virulence attributes of Aspergillus species as well as mechanisms of acquired resistance to antifungal agents. This review represents a concise view of cellular and humoral participants in an immune response to Aspergillus gained mostly from rodent models of aspergillosis. The survey of immune defense mechanisms was given, including the role of innate immune cells (macrophages, neutrophils, monocytes, eosinophils, innate-like lymphocytes) and receptors in antifungal response, the significance of dendritic cells in activation of specific adaptive T cell-mediated immune responses and the regulatory mechanisms of excessive response. Insight into innate immune defense mechanisms gained using non-vertebrate models of infections with Aspergillus sp. was given as well. The contribution of animal models to the current knowledge of immune mechanisms of resistance or susceptibility to these fungi was stressed and the significance of data gained from these models in forming the basis for the design of therapeutic strategies in prevention and/or treatment of aspergillosis was pointed out.

Antimicrobial activity and chemical composition of Brunfelsia uniflora flower oleoresin extracted by supercritical carbon dioxide.

Brunfelsia genus is traditionally utilized in popular medicine due to its antibacterial and antifungal properties to name but a few. However, studies on the antimicrobial activity of Brunfelsia uniflora flower oleoresin have not been found yet. This study aimed to evaluate the chemical composition and antimicrobial activity of B. uniflora flower oleoresin obtained by supercritical carbon dioxide. Oleoresin from the plant dried flowers was obtained by carbon dioxide, and the chemical composition was analyzed by gas chromatographic-mass spectrometry. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) of this oleoresin for seven bacteria and eight fungi were determined using 96-well microtiter plates. The oleoresin MBC for Bacillus cereus, Enterobacter cloacae, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella enterica, and Staphylococcus aureus ranged from 0.01 to 0.08 mg/mL, whereas the controls streptomycin and ampicillin varied from 0.1 and 0.5 mg/mL. The oleoresin MFC for Aspergillus fumigatus, Aspergillus niger, Aspergillus ochraceus, Aspergillus versicolor, Penicillium funiculosum, Penicillium ochrochloron, Penicillium verrucosum var. cyclopium, and Trichoderma viride varied from 0.01 to 0.08 mg/mL, whereas the controls bifonazole and ketoconazole ranged from 0.2 to 3.5 mg/mL. The oleoresin obtained by supercritical carbon dioxide presented bacteriostatic, bactericidal, fungistatic, and fungicidal activities that were higher than the positive controls streptomycin, ampicillin, bifonazole, and ketoconazole. The high antimicrobial activity was related to the high content of (E, E)-geranyllinalool that composes 21.0% of the oleoresin and a possible synergic action with fatty acid esters that made up 50.5% of the oleoresin. The oleoresin antimicrobial activity against common multiresistant bacteria in severe infectious processes as P. aeruginosa or against toxin-producing fungi such as P. ochrochloron or fungi that are difficult to control such as T. viride suggests the development of promising applications of this product in the food, farming, livestock, and pharmaceutical industry.

Antifungal and antibacterial activities of Petroselinum crispum essential oil.

Parsley [Petroselinum crispum (Mill.) Fuss] is regarded as an aromatic, culinary, and medicinal plant and is used in the cosmetic, food, and pharmaceutical industries. However, few studies with conflicting results have been conducted on the antimicrobial activity of parsley essential oil. In addition, there have been no reports of essential oil obtained from parsley aerial parts, except seeds, as an alternative natural antimicrobial agent. Also, microorganism resistance is still a challenge for health and food production. Based on the demand for natural products to control microorganisms, and the re-evaluation of potential medicinal plants for controlling diseases, the objective of this study was to determine the chemical composition and antibacterial and antifungal activities of parsley essential oil against foodborne diseases and opportunistic pathogens. Seven bacteria and eight fungi were tested. The essential oil major compounds were apiol, myristicin, and b-phellandrene. Parsley essential oil had bacteriostatic activity against all tested bacteria, mainly Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica, at similar or lower concentrations than at least one of the controls, and bactericidal activity against all tested bacteria, mainly S. aureus, at similar or lower concentrations than at least one of the controls. This essential oil also had fungistatic activity against all tested fungi, mainly, Penicillium ochrochloron and Trichoderma viride, at lower concentrations than the ketoconazole control and fungicidal activity against all tested fungi at higher concentrations than the controls. Parsley is used in cooking and medicine, and its essential oil is an effective antimicrobial agent.

Antimicrobial activity of the pygidial gland secretion of the troglophilic ground beetle Laemostenus (Pristonychus) punctatus (Dejean, 1828) (Insecta: Coleoptera: Carabidae).

The antimicrobial activity of the pygidial gland secretion released by adult individuals of the troglophilic ground beetle Laemostenus (Pristonychus) punctatus (Dejean, 1828), applying microdilution method with the aim to detect minimal inhibitory concentration, minimal bactericidal concentration and minimal fungicidal concentration, has been investigated. In addition, morphology of the pygidial glands is observed. We have tested 16 laboratory and clinical strains of human pathogens - eight bacterial both gram-positive and gram-negative species and eight fungal species. The pygidial secretion samples have showed antimicrobial properties against all strains of treated bacteria and fungi. Micrococcus flavus proved to be more resistant compared with other bacterial strains. More significant antimicrobial properties of the secretion are observed against Escherichia coli, which proved to be the most sensitive bacteria. Aspergillus fumigatus proved to be the most resistant, while Penicillium ochrochloron and Penicillium verrucosum var. cyclopium the most sensitive micromycetes. Commercial antibiotics Streptomycin and Ampicillin and antimycotics Ketoconazole and Bifonazole, applied as positive controls, showed higher antibacterial properties for all bacterial and fungal strains, except for P. ochrochloron, which proved to be more resistant on Ketoconazole compared with the pygidial gland secretion of L. (P.) punctatus. Apart from the role in ecological aspects, the antimicrobial properties of the tested secretion possibly might have medical significance in the future.

Further in vitro evaluation of antiradical and antimicrobial activities of phytol.

The antiradical activity of phytol was evaluated by electron paramagnetic resonance towards hydroxyl radical (·OH), superoxide anion radical (·O2(-)), methoxy radical (·CH2OH), carbon-dioxide anion radical (·CO2(-)), as well as towards nitric-oxide radical (·NO) and 2,2-diphenyl-1-picrylhydrazyl (·DPPH) radical. It reduced the production of all tested radicals showing more promising activity against ·CO2(-), ·CH2OH and ·DPPH radicals (56%, 50% and 48%, respectively) in comparison with ·NO, ·O2(-) and ·OH radicals (38%, 23% and 15%, respectively). The antimicrobial activity of phytol was evaluated by the microdilution method against eight bacterial and eight fungal strains. To varying degrees, it was proven to be active against all tested bacteria and fungi (MIC 0.003-0.038 mg/mL and MBC 0.013-0.052 mg/mL, MIC 0.008-0.016 mg/mL and MFC 0.090-0.520 mg/mL, respectively). According to the obtained results, medical foods containing phytol may support development of new therapies for heart disease.

Synthesis and biological evaluation of some 5-arylidene-2-(1,3-thiazol-2-ylimino)-1,3-thiazolidin-4-ones as dual anti-inflammatory/antimicrobial agents.

As a part of our ongoing studies in developing new derivatives as dual antimicrobial/anti-inflammatory agents we describe the synthesis of novel 5-arylidene-2-(1,3-thiazol-2-ylimino)-1,3-thiazolidin-4-ones. All newly synthesized compounds were tested for their anti-inflammatory activity using carrageenan mouse paw edema bioassay. Their COX-1/LOX inhibitory activities were also determined. Moreover, all compounds were evaluated for their antimicrobial and antifungal activities against a panel of Gram positive, Gram negative bacteria and moulds. All tested compounds exhibited better antimicrobial activity than commercial drugs, bifonazole, ketoconazole, ampicillin and streptomycin.

Synthesis of novel sulfonamide-1,2,4-triazoles, 1,3,4-thiadiazoles and 1,3,4-oxadiazoles, as potential antibacterial and antifungal agents. Biological evaluation and conformational analysis studies.

The significant antifungal activity of a series of sulfonamide-1,2,4-triazole and 1,3,4-thiazole derivatives against a series of micromycetes, compared to the commercial fungicide bifonazole has been reported. These compounds have also shown a comparable bactericidal effect to that of streptomycin and better activity than chloramphenicol against various bacteria. In view of the potential biological activity of members of the 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole ring systems and in continuation of our search for bioactive molecules, we designed the synthesis of a series of novel sulfonamide-1,2,4-triazoles, -1,3,4-thiadiazoles and -1,3,4-oxadiazoles emphasizing, in particular, on the strategy of combining two chemically different but pharmacologically compatible molecules (the sulfomamide nucleus and the five member) heterocycles in one frame. Synthesized compounds were tested in vitro for antibacterial and antifungal activity and some analogues exhibited very promising results especially as antifungal agents. In order to explain structure-activity relationships, conformational analysis was performed for active and less active analogues using NMR spectroscopy and molecular modeling techniques. Furthermore, molecular properties which can be further used as descriptors for SAR studies, were predicted for the synthesized analogues. In general, antifungal activity seems to depend more on the triazol-3-thione moiety rather than the different length of the alkyl chain substitutions.

Novel (E)-1-(4-methyl-2-(alkylamino)thiazol-5-yl)-3-arylprop-2-en-1-ones as potent antimicrobial agents.

New (E)-1-(4-methyl-2-(alkylamino)thiazol-5-yl)-3-arylprop-2-en-1-ones, unsubstituted or carrying fluoro, bromo, methoxy, nitro, methyl and chloro groups on the benzene ring, were synthesized and assayed in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria and fungi. The compounds were very potent towards all tested microorganisms and in most cases their activity was better than that of reference drugs.

Thiazole-based chalcones as potent antimicrobial agents. Synthesis and biological evaluation.

As part of ongoing studies in developing new antimicrobials, we report the synthesis of a new class of structurally novel derivatives, that incorporate two known bioactive structures a thiazole and chalcone, to yield a class of compounds with interesting antimicrobial properties. Evaluation of antibacterial activity showed that almost all the compounds exhibited greater activity than reference drugs and thus could be promising novel drug candidates.

Morphological characteristics and mycelial compatibility of different Mycogone perniciosa isolates.

The major disease of the cultivated mushroom Agaricus bisporus Lange (Imb) in Serbian mushroom farms is wet bubble caused by the fungus Mycogone perniciosa (Magnus) Delacr. In this study we report the morpho-physiological characteristics and inter-relationships between colonies of five isolates of M. perniciosa. The results suggest that mycelial compatibility could serve as an additional parameter for a more reliable determination of different pathotypes of M. perniciosa.

Antifungal activity of the essential oil of Thymus vulgaris L. and thymol on experimentally induced dermatomycoses.

The in vivo evaluation of the toxicological and antifungal activity of the essential oil of Thymus vulgaris L. and its main component thymol was made on 2-month-old male Wistar rats. We examined the therapeutic potency against experimentally induced dermatomycoses in rats, using the most frequent dermatomycetes, Trichophyton mentagrophytes, T. rubrum, and T. tonsurans. The therapeutic efficacy of a 1% solution of the essential oil of Thymus vulgaris and thymol as well as the commercial preparation bifonazole was evaluated. During the 37-day observation period the oil-treated animals were cured.