ABSTRACT
BACKGROUND: In general, fungal species are characterized by their opportunistic character and can trigger various infections in immunocompromised hosts. The emergence of infections associated with high mortality rates is due to the resistance mechanisms that these species develop. METHODS: This phenomenon of resistance denotes the need for the development of new and effective therapeutic approaches. In this paper, we report the investigation of the antioxidant and antifungal behavior of dimeric naphthoquinones derived from lawsone whose antimicrobial and antioxidant potential has been reported in the literature. RESULTS: Seven fungal strains were tested, and the antioxidant potential was tested using the combination of the methodologies: reducing power, total antioxidant capacity and cyclic voltammetry. Molecular docking studies (PDB ID 5V5Z and 1EA1) were conducted which allowed the derivation of structureactivity relationships (SAR). Compound 1-i, derived from 3-methylfuran-2-carbaldehyde showed the highest antifungal potential with an emphasis on the inhibition of Candida albicans species (MIC = 0.5 µg/mL) and the highest antioxidant potential. CONCLUSION: A combination of molecular modeling data and in vitro assays can help to find new solutions to this major public health problem.
Subject(s)
Antifungal Agents/pharmacology , Antioxidants/pharmacology , Candida albicans/drug effects , Molecular Docking Simulation , Naphthoquinones/pharmacology , Quantum Theory , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , DNA Repair , Dimerization , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Molecular Structure , Naphthoquinones/chemical synthesis , Naphthoquinones/chemistry , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Structure-Activity RelationshipABSTRACT
Several enzymatic reactions of heteroatom-containing compounds have been explored as unnatural substrates. Considerable advances related to the search for efficient enzymatic systems able to support a broader substrate scope with high catalytic performance are described in the literature. These reports include mainly native and mutated enzymes and whole cells biocatalysis. Herein, we describe the historical background along with the progress of biocatalyzed reactions involving the heteroatom(S, Se, B, P and Si) from hetero-organic substrates.
Subject(s)
Bacteria/metabolism , Biocatalysis , Biotransformation , Enzymes/metabolism , Fungi/metabolism , Biosensing Techniques , Enzymes/chemistry , Substrate SpecificityABSTRACT
ABSTRACT Several enzymatic reactions of heteroatom-containing compounds have been explored as unnatural substrates. Considerable advances related to the search for efficient enzymatic systems able to support a broader substrate scope with high catalytic performance are described in the literature. These reports include mainly native and mutated enzymes and whole cells biocatalysis. Herein, we describe the historical background along with the progress of biocatalyzed reactions involving the heteroatom(S, Se, B, P and Si) from hetero-organic substrates.
Subject(s)
Bacteria/metabolism , Biotransformation , Enzymes/metabolism , Biocatalysis , Fungi/metabolism , Substrate Specificity , Biosensing Techniques , Enzymes/chemistryABSTRACT
By a targeted enzyme engineering approach, we were able to create an efficient NADPH oxidase from a monooxygenase. Intriguingly, replacement of only one specific single amino acid was sufficient for such a monooxygenase-to-oxidase switch-a complete transition in enzyme activity. Pre-steady-state kinetic analysis and elucidation of the crystal structure of the C65D PAMO mutant revealed that the mutation introduces small changes near the flavin cofactor, resulting in a rapid decay of the peroxyflavin intermediate. The engineered biocatalyst was shown to be a thermostable, solvent tolerant, and effective cofactor-regenerating biocatalyst. Therefore, it represents a valuable new biocatalytic tool.
