The Relevance and Insights on 1,4-Naphthoquinones as Antimicrobial and Antitumoral Molecules: A Systematic Review.

Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary metabolites found in plants and are used in traditional medicine to treat diverse human diseases. Considering this, the synthesis of naphthoquinone derivatives has been explored to contain compounds with potential biological activity. It has been reported that the chemical modification of naphthoquinones improves their pharmacological properties by introducing amines, amino acids, furan, pyran, pyrazole, triazole, indole, among other chemical groups. In this systematic review, we summarized the preparation of nitrogen naphthoquinones derivatives and discussed their biological effect associated with redox properties and other mechanisms. Preclinical evaluation of antibacterial and/or antitumoral naphthoquinones derivatives is included because cancer is a worldwide health problem, and there is a lack of effective drugs against multidrug-resistant bacteria. The information presented herein indicates that naphthoquinone derivatives could be considered for further studies to provide drugs efficient in treating cancer and multidrug-resistant bacteria.

Use of a Cellulase from Trichoderma reesei as an Adjuvant for Enterococcus faecalis Biofilm Disruption in Combination with Antibiotics as an Alternative Treatment in Secondary Endodontic Infection.

Apical periodontitis is an inflammation leading to the injury and destruction of periradicular tissues. It is a sequence of events that starts from root canal infection, endodontic treatment, caries, or other dental interventions. Enterococcus faecalis is a ubiquitous oral pathogen that is challenging to eradicate because of biofilm formation during tooth infection. This study evaluated a hydrolase (CEL) from the fungus Trichoderma reesei combined with amoxicillin/clavulanic acid as a treatment against a clinical E. faecalis strain. Electron microscopy was used to visualize the structure modification of the extracellular polymeric substances. Biofilms were developed on human dental apices using standardized bioreactors to evaluate the antibiofilm activity of the treatment. Calcein and ethidium homodimer assays were used to evaluate the cytotoxic activity in human fibroblasts. In contrast, the human-derived monocytic cell line (THP-1) was used to evaluate the immunological response of CEL. In addition, the secretion of the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine IL-10 were measured by ELISA. The results demonstrated that CEL did not induce the secretion of IL-6 and TNF-α when compared with lipopolysaccharide used as a positive control. Furthermore, the treatment combining CEL with amoxicillin/clavulanic acid showed excellent antibiofilm activity, with a 91.4% reduction in CFU on apical biofilms and a 97.6% reduction in the microcolonies. The results of this study could be used to develop a treatment to help eradicate persistent E. faecalis in apical periodontitis.

Interactions of Antibacterial Naphthoquinones with Mesoporous Silica Surfaces: A Physicochemical and Theoretical Approach.

1,4-naftoquinone (NQ) molecules have been extensively evaluated as potent antibacterial compounds; however, their use is limited, since they have low water solubility and exhibit toxicities in healthy eukaryotic cells. A possible path to overcoming these challenges is the use of particulate vehicles, such as SBA-15, which is a biocompatible and biodegradable mesoporous silica material, that may enhance drug delivery and decrease dosages. In this work, an isotherm model-based adsorption of three NQs into SBA-15 microparticles was evaluated. Interactions between NQs and SBA-15 microparticles were modeled at the B3LYP/6-31+G(d,p) level of theory to understand the nature of such interactions. The results demonstrated that the adsorption of NQ, 2NQ, and 5NQ into SBA-15 fit the Freundlich adsorption model. According to theorical studies, physisorption is mediated by hydrogen bonds, while the most stable interactions occur between the carbonyl group of NQ and silica surfaces. Both experimental and theoretical results contribute to a deeper understanding of the use of SBA-15 or similar particles as nanovehicles in such a way that NQs can be modified in carbonyl or C3 to enhance adsorptions. The theoretical and experimental results were in accordance and contribute to a deeper understanding of how interactions between NQ-type molecules and SiO2 materials occur.

Synthesis and Antimicrobial Evaluation of Amino Acid Naphthoquinone Derivatives as Potential Antibacterial Agents.

BACKGROUND: The synthesis and biological evaluation of 1,4-naphthoquinone derivatives are of great interest since these compounds exhibit strong antibacterial, antifungal, antimalarial, and anticancer activities. The electronic properties of naphthoquinones are usually modulated by attaching functional groups containing nitrogen, oxygen, and sulfur atoms, which tune their biological potency and selectivity. METHODS: A series of 13 amino acid 1,4-naphthoquinone derivatives was synthesized under assisted microwave and ultrasound conditions. The antibacterial activity of compounds was tested against American Type Culture Collection (ATCC): Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis, as well as 2 multidrug resistant pathogens: E. coli and S. aureus from clinical isolated. Minimal inhibitory concentration (MIC) was determined using the broth microdilution method. RESULTS: MIC of derivatives 4-11, 14, and 16 showed antimicrobial activity against Gram-positive and Gram-negative bacteria. Antimicrobial activities of the compounds 4-8 and 14 were ≤MIC 24.7 µg mL-1 against all the reference strains; even more, compound 6 showed the most potent activity with an MIC of 3.9 µg mL-1 on S. aureus. On the clinical isolated, the compounds 7, 8, and 14 showed an MIC of 49.7 and 24.7 µg mL-1 against S. aureus and E. coli, respectively. About ADME properties and Osiris analysis, the compounds 4-16 presented high gastrointestinal absorption and good characteristics for oral bioavailability, and compound 14 was the less toxic. CONCLUSION: Amino acid 1,4-naphthoquinone derivatives showed good in vitro antibacterial activity against clinical strains, and modifications on C-3 with a chloride atom enhanced the efficiency against the same pathogens.

Naphthoquinones: biological properties and synthesis of lawsone and derivatives- a structured review / Naftoquinonas: propiedades biológicas y síntesis de lawsona y derivados ­ una revisión estructurada

Background: Naphthoquinones are natural pigments that are widely distributed in nature and have important biological activities. Lawsone (2-hydroxy-1,4-naphthoquinone) and its synthetic derivatives, and especially those containing nitrogen, have promising potential for the treatment of different diseases due to their antibacterial, antifungal, antiviral, antitumor and antiparasitic effects, and for pest control via their molluscicidal and insecticidal activities. Their pharmacological activities and mechanisms of action are related to their oxide/reduction and acid/base properties, and can be modulated by directly adding a substituted to the 1,4-naphthoquinone ring. Due to this, naphthoquinones and their derivatives are at the center of multiple areas of research. In this manuscript, we present a structured review of lawsone, a hydroxyl derivative of naphthoquinone, and discuss relevant reports about the chemistry and synthesis of derivatives. Finally, we present the pharmacological activities and mechanism of action reported. Objective: The purpose of this review is to present recent reports from the literature about the chemistry, synthesis and pharmacological properties of lawsone and its amine derivatives. Methods: This structured review presents a discussion about lawsone literature over the last ten years. The most representative studies including those about the chemistry of lawsone, the synthesis of its derivatives, and pharmacological properties were identified and selected. The information has been compiled, organized and presented into logical topics in order to provide a current review for the field of lawsone chemistry. Results: A general overview of the principal aspects of lawsone chemistry, the synthesis of its derivatives and their pharmacological activities and mechanism of action has been obtained. This provides researchers in the area with a framework from which to investigate further. Conclusions: Lawsone and its derivatives have promising potential for treating several diseases due to their antibacterial, antifungal, antiviral, antitumor and antiparasitic effects and have the potential to control pests via their molluscicidal and insecticidal properties. For this reason, it would be of interest to evaluate the synthetic derivatives of this compound for their pharmacologic actions; in the future, synthetic derivatives of lawsone could potentially be used to treat disease and be used as pesticides.