Nejvíce citovaný článek - PubMed ID 11902656
Ring substituted 3-phenyl-1-(2-pyrazinyl)-2-propen-1-ones as potential photosynthesis-inhibiting, antifungal and antimycobacterial agents
The greatest threat and medicinal impact within gram-positive pathogens are posed by two bacterial genera, Staphylococcus and Enterococcus. Chalcones have a wide range of biological activities and are recognized as effective templates in medicinal chemistry. This study provides comprehensive insight into the anti-staphylococcal and anti-enterococcal activities of two recently published brominated and chlorinated pyrazine-based chalcones, CH-0y and CH-0w. Their effects against 4 reference and 12 staphylococcal and enterococcal clinical isolates were evaluated. Bactericidal action, the activity in combination with selected conventional antibiotics, the study of post-antimicrobial effect (PAE, PAE/SME), and in vitro and in vivo toxicity, were included. In CH-0y, anti-staphylococcal activity ranging from MIC = 15.625 to 62.5 μM, and activity against E. faecium from 31.25 to 62.5 μM was determined. In CH-0w, anti-staphylococcal activity ranging from 31.25 to 125 μM, and activity against E. faecium and E. faecalis (62.5 μM) was revealed. Both CH-0y and CH-0w showed bactericidal action, beneficial impact on bacterial growth delay within PAE and PAE/SME studies, and non/low toxicity in vivo. Compared to CH-0w, CH-0y seems to have higher anti-staphylococcal and less toxic potential. In conclusion, chalcones CH-0y and CH-0w could be considered as structural pattern for future adjuvants to selected antibiotic drugs.
Chalcones are polyphenolic secondary metabolites of plants, many of which have antioxidant activity. Herein, a set of 26 synthetic chalcone derivatives with alkyl substituted pyrazine heterocycle A and four types of the monophenolic ring B, were evaluated for the potential radical scavenging and antioxidant cellular capacity influencing the growth of cells exposed to H₂O₂. Before that, compounds were screened for cytotoxicity on THP-1 and HepG2 cell lines. Most of them were not cytotoxic in an overnight MTS assay. However, three of them, 4a, 4c and 4e showed 1,1-diphenyl-2-picrylhydrazyl (DPPH●) radical scavenging activity, through single electron transfer followed by a proton transfer (SET-PT) mechanism as revealed by density functional theory (DFT) modeling. DFT modeling of radical scavenging mechanisms was done at the SMD//(U)M052X/6-311++G** level. The in vitro effects of 4a, 4c and 4e on the growth of THP-1 cells during four days pre- or post-treatment with H₂O₂ were examined daily with the trypan blue exclusion assay. Their various cellular effects reflect differences in their radical scavenging capacity and molecular lipophilicity (clogP) and depend upon the cellular redox status. The applied simple in vitro-in silico screening cascade enables fast identification and initial characterization of potent radical scavengers.
- Klíčová slova
- DFT, antioxidant, chalcone-like, in silico, in vitro, pyrazine, radical scavenging,
- Publikační typ
- časopisecké články MeSH
Two novel thiosemicarbazones and eight novel 2-{[1-(5-alkyl/arylalkylpyrazin-2-yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones were prepared and tested against a panel of eight fungal strains-Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton interdigitale 445. 1,3-Thiazolidin-4-ones exhibited activity against all strains, the most potent derivative was 2-{[1-(5-butylpyrazin-2-yl)ethylidene]hydrazono}e-1,3-thiazolidin-4-one. Susceptibility of C. glabrata to the studied 1,3-thiazolidin-4-ones (minimum inhibitory concentrations (MICs) were in the range 0.57 to 2.78 mg/L) is of great interest as this opportunistic pathogen is poorly susceptible to azoles and becomes resistant to echinocandins. Antifungal potency of thiosemicarbazones was slightly lower than that of 1,3-thiazolidin-4-ones.
- Klíčová slova
- 1,3-thiazolidin-4-ones, Candida glabrata, acetylpyrazine, antifungal, thiosemicarbazones,
- MeSH
- antifungální látky chemická syntéza chemie farmakologie MeSH
- Aspergillus účinky léků MeSH
- Candida účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Mucorales účinky léků MeSH
- thiazolidindiony chemická syntéza chemie farmakologie MeSH
- thiosemikarbazony chemická syntéza chemie farmakologie MeSH
- Trichophyton účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antifungální látky MeSH
- thiazolidindiony MeSH
- thiosemikarbazony MeSH
Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal and antimycobacterial activity. The highest potency was exhibited by derivatives with electron withdrawing groups (EWG) in positions 2 and 4 of the ring B. As halogens also have electron withdrawing properties, novel halogenated derivatives were prepared by Claisen-Schmidt condensation. All compounds were submitted for evaluation of their antifungal and antibacterial activity, including their antimycobacterial effect. In the antifungal assay against eight strains of selected fungi, growth inhibition of Candida glabrata and Trichophyton interdigitale (formerly T. mentagrophytes) was shown by non-alkylated derivatives with 2-bromo or 2-chloro substitution. In the panel of selected bacteria, 2-chloro derivatives showed the highest inhibitory effect on Staphylococcus sp. In addition, all products were also screened for their antimycobacterial activity against Mycobacterium tuberculosis H37RV My 331/88, M. kansasii My 235/80, M. avium 152/80 and M. smegmatis CCM 4622. Some of the examined compounds, inhibited growth of M. kansasii and M. smegmatis with minimum inhibitory concentrations (MICs) comparable with those of isoniazid.
- Klíčová slova
- antibacterial, antifungal, antimycobacterial, chalcone, halogenated, pyrazine,
- MeSH
- antiinfekční látky * chemická syntéza chemie farmakologie MeSH
- Candida glabrata růst a vývoj MeSH
- chalkon * chemická syntéza chemie farmakologie MeSH
- halogenované uhlovodíky * chemická syntéza chemie farmakologie MeSH
- Mycobacterium růst a vývoj MeSH
- pyraziny * chemická syntéza chemie farmakologie MeSH
- Trichophyton růst a vývoj MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiinfekční látky * MeSH
- chalkon * MeSH
- halogenované uhlovodíky * MeSH
- pyraziny * MeSH
Infectious diseases, such as tuberculosis and invasive mycoses, represent serious health problems. As a part of our long-term efforts to find new agents for the treatment of these diseases, a new series of pyrazine analogs of chalcones bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The structures of the compounds were corroborated by IR and NMR spectroscopy and their purity confirmed by elemental analysis. The susceptibility of eight fungal strains to the studied compounds was tested. The results have been compared with the activity of some previously reported propyl derivatives. The only strain that was susceptible to the studied compounds was Trichophyton mentagrophytes. It was found that replacing a non-branched propyl with a branched isopropyl did not have a decisive and unequivocal influence on the in vitro antifungal activity against T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes comparable with that of fluconazole was exhibited by nitro-substituted derivatives. Unfortunately, no compound exhibited efficacy comparable with that of terbinafine, which is the most widely used agent for treating mycoses caused by dermatophytes. Some of the prepared compounds were assayed for antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was also displayed by nitro-substituted compounds. The results of the present study are in a good agreement with our previous findings and confirm the positive influence of electron-withdrawing groups on the B-ring of chalcones on the antifungal and antimycobacterial activity of these compounds.
- MeSH
- antifungální látky chemická syntéza chemie farmakologie MeSH
- antituberkulotika chemická syntéza chemie farmakologie MeSH
- Cercopithecus aethiops MeSH
- chalkonoidy chemická syntéza chemie farmakologie MeSH
- houby klasifikace účinky léků MeSH
- magnetická rezonanční spektroskopie s uhlíkem 13C MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- protonová magnetická rezonanční spektroskopie MeSH
- pyraziny chemie MeSH
- spektrofotometrie infračervená MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antifungální látky MeSH
- antituberkulotika MeSH
- chalkonoidy MeSH
- pyraziny MeSH
