The use of natural compounds is becoming increasingly popular among patients, and there is a renewed interest among scientists in nature-based bioactive agents. Traditionally, herbal drugs can be taken directly in the form of teas/decoctions/infusions or as standardized extracts. However, the disadvantages of natural compounds, especially essential oils, are their instability, limited bioavailability, volatility, and often irritant/allergenic potential. However, these active substances can be stabilized by encapsulation and administered in the form of nanoparticles. This brief overview summarizes the latest results of the application of nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers used as drug delivery systems of herbal essential oils or used directly for their individual secondary metabolites applicable in cancer therapy. Although the discussed bioactive agents are not typical compounds used as anticancer agents, after inclusion into the aforesaid formulations improving their stability and bioavailability and/or therapeutic profile, they indicated anti-tumor activity and became interesting agents with cancer treatment potential. In addition, co-encapsulation of essential oils with synthetic anticancer drugs into nanoformulations with the aim to achieve synergistic effect in chemotherapy is discussed.

• Klíčová slova
• anticancer activity, essential oils, herbal drugs, liposomes, nanoemulsions, nanostructured lipid carriers, solid lipid nanoparticles,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Due to the urgent need of innovation in the antimalarial therapeutic arsenal, a series of thirty-seven ring-substituted N-arylcinnamanilides prepared by microwave-assisted synthesis were subjected to primary screening against the chloroquine-sensitive strain of P. falciparum 3D7/MRA-102. The lipophilicity of all compounds was experimentally determined as the logarithm of the capacity factor k, and these data were subsequently used in the discussion of structure-activity relationships. Among the screened compounds, fourteen derivatives exhibited IC50 from 0.58 to 31 µM, whereas (2E)-N-(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide (24) was the most effective agent (IC50 = 0.58 µM). In addition, (2E)-N-[2,6-dibromo-4-(trifluoromethyl)- phenyl]-3-phenylprop-2-enamide (36), (2E)-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-phenylprop- 2-enamide (18), (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide (23), and (2E)-3-phenyl-N-(3,4,5-trichlorophenyl)prop-2-enamide (33) demonstrated efficacy in the IC50 range from 2.0 to 4.3 µM, comparable to the clinically used standard chloroquine. The results of a cell viability screening performed using THP1-Blue™ NF-κB cells showed that none of these highly active compounds displayed any significant cytotoxic effect up to 20 μM, which makes them promising Plasmodium selective substances for further investigations.

• Klíčová slova
• Plasmodium, antiplasmodial activity, cinnamanilides, structure-activity relationships,
• MeSH
• antagonisté kyseliny listové * MeSH
• antimalarika * farmakologie   MeSH
• chlorochin farmakologie   MeSH
• lidé MeSH
• tropická malárie * MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté kyseliny listové * MeSH
• antimalarika * MeSH
• chlorochin MeSH

Microbial infections caused by a variety of drug-resistant microorganisms are more common, but there are fewer and fewer approved new antimicrobial chemotherapeutics for systemic administration capable of acting against these resistant infectious pathogens. Formulation innovations of existing drugs are gaining prominence, while the application of nanotechnologies is a useful alternative for improving/increasing the effect of existing antimicrobial drugs. Nanomaterials represent one of the possible strategies to address this unfortunate situation. This review aims to summarize the most current results of nanoformulations of antibiotics and antibacterial active nanomaterials. Nanoformulations of antimicrobial peptides, synergistic combinations of antimicrobial-active agents with nitric oxide donors or combinations of small organic molecules or polymers with metals, metal oxides or metalloids are discussed as well. The mechanisms of actions of selected nanoformulations, including systems with magnetic, photothermal or photodynamic effects, are briefly described.

• Klíčová slova
• antibiotics, metalloids, metals, nanoformulations, nanomaterials, nanoparticles, polymers,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against Staphylococcus aureus and clinical isolates of methicillin-resistant S. aureus (MRSA). (2E)-N-[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series 1. (2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2E)-3-(3,4-dichlorophenyl)-N-[3-(trifluoromethyl)phenyl]prop-2-enamide, (2E)-3-(3,4-dichloro- phenyl)-N-[4-(trifluoromethyl)phenyl]prop-2-enamide and (2E)-3-(3,4-dichlorophenyl)- N-[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series 2 and in addition to activity against S. aureus and MRSA were highly active against Enterococcus faecalis and vancomycin-resistant E. faecalis isolates and against fast-growing Mycobacterium smegmatis and against slow-growing M. marinum, M. tuberculosis non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages.

• Klíčová slova
• antimicrobial activity, cinnamamides, cytotoxicity, lipophilicity, structure-activity relationships,
• MeSH
• ampicilin farmakologie   MeSH
• antibakteriální látky farmakologie   MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium tuberculosis * MeSH
• prasata MeSH
• savci MeSH
• stafylokokové infekce * MeSH
• Staphylococcus aureus MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ampicilin MeSH
• antibakteriální látky MeSH

Despite the established treatment regimens, tuberculosis remains an alarming threat to public health according to WHO. Novel agents are needed to overcome the increasing rate of resistance and perhaps achieve eradication. As part of our long-term research on pyrazine derived compounds, we prepared a series of their ortho fused derivatives, N-phenyl- and N-benzyl quinoxaline-2-carboxamides, and evaluated their in vitro antimycobacterial activity. In vitro activity against Mycobacterium tuberculosis H37Ra (represented by minimum inhibitory concentration, MIC) ranged between 3.91-500 µg/mL, with most compounds having moderate to good activities (MIC < 15.625 µg/mL). The majority of the active compounds belonged to the N-benzyl group. In addition to antimycobacterial activity assessment, final compounds were screened for their in vitro cytotoxicity. N-(naphthalen-1-ylmethyl)quinoxaline-2-carboxamide (compound 29) was identified as a potential antineoplastic agent with selective cytotoxicity against hepatic (HepG2), ovarian (SK-OV-3), and prostate (PC-3) cancer cells lines. Molecular docking showed that human DNA topoisomerase and vascular endothelial growth factor receptor could be potential targets for 29.

• Klíčová slova
• Mycobacterium tuberculosis, antimycobacterial, cytotoxicity, molecular docking, pyrazinamide, quinoxaline, tuberculosis,
• Publikační typ
• časopisecké články MeSH

Series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate and 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate showed antistaphylococcal (MICs = 42 µM against MRSA) and antimycobacterial (MICs = 21 µM) activity against the tested strains comparable with or higher than that of the standards ampicillin and isoniazid. In the case of bulkier carbamate tails (R > propyl/isopropyl), the activity was similar (MICs ca. 70 µM). Screening of the cytotoxicity of both of the most effective compounds was performed using THP-1 cells, and no significant lethal effect was observed (LD50 >30 µM). The structure-activity relationships are discussed.

• Klíčová slova
• carbamates, hydroxynaphthalene-carboxamides, in vitro antibacterial activity, in vitro antimycobacterial activity, in vitro cytotoxicity assay, structure-activity relationships,
• MeSH
• antiinfekční látky * chemická syntéza   chemie   farmakologie   MeSH
• cytotoxiny * chemická syntéza   chemie   farmakologie   MeSH
• karbamáty * chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus růst a vývoj   MeSH
• Mycobacterium tuberculosis růst a vývoj   MeSH
• nádorové buněčné linie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiinfekční látky * MeSH
• cytotoxiny * MeSH
• karbamáty * MeSH

A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, M. kansasii and M. smegmatis. Screening of the cytotoxicity of the compounds was performed using human monocytic leukemia THP-1 cells. Some of the tested compounds showed antimycobacterial activity comparable with or higher than that of rifampicin. For example, 2-hydroxy-N-(4-propoxyphenyl)-naphthalene-1-carboxamide showed the highest activity (MIC = 12 µM) against M. tuberculosis with insignificant cytotoxicity. N-[3-(But-2-yloxy)phenyl]- and N-[4-(but-2-yloxy)phenyl]-2-hydroxy-naphthalene-1-carboxamide demonstrated high activity against all tested mycobacterial strains and insignificant cytotoxicity. N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides demonstrated rather high effect against M. smegmatis and M. kansasii and strong antiproliferative effect against the human THP-1 cell line. Lipophilicity was found as the main physicochemical parameter influencing the activity. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Structure-activity relationships are discussed.

• Klíčová slova
• MTT assay, hydroxynaphthalenecarboxamides, in vitro antimycobacterial activity, lipophilicity, structure-activity relationships,
• MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• buněčné linie MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mikrobiální viabilita účinky léků   MeSH
• molekulární struktura MeSH
• Mycobacterium kansasii účinky léků   MeSH
• Mycobacterium smegmatis účinky léků   MeSH
• Mycobacterium tuberculosis účinky léků   MeSH
• naftoly chemická syntéza   chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• naftoly MeSH