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.

• Keywords
• anticancer activity, essential oils, herbal drugs, liposomes, nanoemulsions, nanostructured lipid carriers, solid lipid nanoparticles,
• Publication type
• Journal Article MeSH
• Review MeSH

A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15-5.57 µM) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 µM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 µM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 µM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.

• Keywords
• Michael acceptors, antimicrobial activity, cinnamamides, cytotoxicity, docking study, lipophilicity, structure–activity relationships,
• MeSH
• Anti-Bacterial Agents pharmacology   chemistry   MeSH
• Cinnamates pharmacology   chemistry   MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus * MeSH
• Microbial Sensitivity Tests MeSH
• Staphylococcal Infections * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Cinnamates MeSH
• cinnamic acid MeSH Browser

A new method for modifying the structure of tetracyclic quinobenzothiazinium derivatives has been developed, allowing introduction of various substituents at different positions of the benzene ring. The method consists of reacting appropriate aniline derivatives with 5,12-(dimethyl)thioquinantrenediinium bis-chloride. A series of new quinobenzothiazine derivatives was obtained with propyl, allyl, propargyl and benzyl substituents in 9, 10 and 11 positions, respectively. The structure of the obtained compounds was analyzed by 1H and 13C NMR (HSQC, HMBC) and X-ray analysis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). In addition, all the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. 9-Benzyloxy-5-methyl-12H-quino [3,4-b][1,4]benzothiazinium chloride (6j), 9-propoxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6a) and 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6d) demonstrated high activity against the entire tested microbial spectrum. The activities of the compounds were comparable with oxacillin, tetracycline and ciprofloxacinagainst staphylococcal strains and with rifampicin against both mycobacterial strains. Compound 6j had a significant effect on the inhibition of bacterial respiration as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity, but also bactericidal activity. Preliminary in vitro cytotoxicity screening of the compounds performed using normal human dermal fibroblasts (NHDF) proved that the tested compounds showed an insignificant cytotoxic effect on human cells (IC50 > 37 µM), making these compounds interesting for further investigation. Moreover, the intermolecular similarity of novel compounds was analyzed in the multidimensional space (mDS) of the structure/property-related in silico descriptors by means of principal component analysis (PCA) and hierarchical clustering analysis (HCA), respectively. The distance-oriented structure/property distribution was related with the experimental lipophilic data.

• Keywords
• antibacterial activity, azaphenothiazines, cytotoxicity, descriptor-based similarity analysis, phenothiazine,
• MeSH
• Anti-Bacterial Agents chemistry   MeSH
• Chlorides pharmacology   MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus * MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Chlorides MeSH

A series of eleven benzylated intermediates and eleven target compounds derived from salicylanilide were tested against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as reference strains and against three clinical isolates of methicillin-resistant S. aureus (MRSA) and three isolates of vancomycin-resistant E. faecalis. In addition, the compounds were evaluated against Mycobacterium tuberculosis H37Ra and M. smegmatis ATCC 700084. The in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line THP-1. The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. The benzylated intermediates were found to be completely biologically inactive. Of the final eleven compounds, according to the number of amide groups in the molecule, eight are diamides, and three are triamides that were inactive. 5-Chloro-2-hydroxy-N-[(2S)- 4-(methylsulfanyl)-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (3e) and 5-chloro-2-hydroxy-N-[(2S)-(4-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino)pentan-2-yl)benzamide (3f) showed the broadest spectrum of activity against all tested species/isolates comparable to the used standards (ampicillin and isoniazid). Six diamides showed high antistaphylococcal activity with MICs ranging from 0.070 to 8.95 μM. Three diamides showed anti-enterococcal activity with MICs ranging from 4.66 to 35.8 μM, and the activities of 3f and 3e against M. tuberculosis and M. smegmatis were MICs of 18.7 and 35.8 μM, respectively. All the active compounds were microbicidal. It was observed that the connecting linker between the chlorsalicylic and 4-CF3-anilide cores must be substituted with a bulky and/or lipophilic chain such as isopropyl, isobutyl, or thiabutyl chain. Anticancer activity on THP-1 cells IC50 ranged from 1.4 to >10 µM and increased with increasing lipophilicity.

• Keywords
• antimicrobial activity, cytotoxicity, lipophilicity, peptidomimetics, salicylamide, structure–activity relationships,
• MeSH
• Ampicillin MeSH
• Anilides MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Benzamides MeSH
• Isoniazid MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus * MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium tuberculosis * MeSH
• Peptidomimetics * MeSH
• Salicylanilides pharmacology   MeSH
• Vancomycin MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Ampicillin MeSH
• Anilides MeSH
• Anti-Bacterial Agents MeSH
• Benzamides MeSH
• Isoniazid MeSH
• Peptidomimetics * MeSH
• salicylanilide MeSH Browser
• Salicylanilides MeSH
• Vancomycin MeSH