ABSTRACT
We present the development of surfactant-free, silica-free and fully biobased oil-in-water antimicrobial Pickering emulsions, based on the self-assembly of ß-cyclodextrin and phytoantimicrobial oils (terpinen-4-ol or carvacrol). Undecylenic acid (UA), derived from castor oil, can be used as bio-based drug to treat fungal infection, but is less effective than petroleum-based drugs as azole derivatives. To maximize its antifungal potential, we have incorporated UA in fully biobased Pickering emulsions. These emulsions are effective against fungi, Gram-positive and Gram-negative bacteria. The carvacrol emulsion charged with UA is +390 % and +165 % more potent against methicillin-resistant S. aureus (MRSA), compared to UA and azole-based commercial formulations. Moreover, this emulsion is up to +480 % more efficient that UA ointment against C. albicans. Finally, remarkable eradication of E. coli and MRSA biofilms was obtained with this environmental-friendly emulsion.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Cymenes/pharmacology , Undecylenic Acids/pharmacology , beta-Cyclodextrins/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Candida albicans/drug effects , Castor Oil/chemistry , Cymenes/chemical synthesis , Cymenes/chemistry , Dose-Response Relationship, Drug , Emulsions/chemical synthesis , Emulsions/chemistry , Emulsions/pharmacology , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Undecylenic Acids/chemical synthesis , Undecylenic Acids/chemistry , beta-Cyclodextrins/chemical synthesis , beta-Cyclodextrins/chemistryABSTRACT
The increased prevalence of antibiotic-resistant bacteria is a critical issue for human health. Developing new antibiotic agents is vital for fighting persistent infections and lowering mortality rates. In this study, we designed lutidine-disubstituted bis-benzimidazolium salts (lutidine-bis-benzimidazolium core with octyl, adamantyl, and cholesteryl lipophilic side chains), and tested their antimicrobial activity, their capacity to inhibit planktonic bacterial and fungal growth, and their ability to inhibit the formation of or disrupt mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms. The antibiofilm activity of these salts was analyzed in terms of their lipophilicity, capacity to induce transmembrane ion transport, perturbation of the cellular membrane, and mechanism of action in the phospholipid bilayer. The synthesized compounds were not active against MRSA biofilms, as the formation of transmembrane channels had no effect on the integrity of the extracellular polymeric substance matrix and only octyl and adamantyl derivatives possessed the capacity to inhibit biofilm formation. The synthesized derivatives could be used as lead candidates for the development of anti-MRSA agents.
Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Biofilms/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Bacillus thuringiensis/drug effects , Bacillus thuringiensis/physiology , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Biofilms/growth & development , Candida/drug effects , Candidiasis/drug therapy , Drug Design , Escherichia coli/drug effects , Escherichia coli/physiology , Humans , Methicillin-Resistant Staphylococcus aureus/physiology , Microbial Sensitivity Tests , Models, Molecular , Salts/chemistry , Salts/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiologyABSTRACT
Novel thyroxine analogs with hindered phenol, amino and carboxylic acid groups have been synthesized and the effects of the synthesized compounds on angiogenesis using the chick chorioallantoic membrane and mouse matrigel models have been tested. Pharmacological profiles revealed that thyroxine tolerates numerous modifications on the amino group and remains active. These results provide the rationale for the selection of a novel thyroxine nanoparticle precursor.
