Lawsone Co-Crystals Loaded Antifungal Gel for Cutaneous Candidiasis

Aim: An attempt was made to improve the solubility and to achieve better penetration of antifungal agent lawsone a poorly water-soluble naphthoquinone, derivative via co-crystallization to treat cutaneous candidiasis. Methodology: The co-crystals of lawsone were prepared using benzoic acid as co former by solvent crystallization method. The formulated co-crystals were assessed for different parameters namely, saturation solubility, thermal properties, crystalline nature, particle size and its antifungal activity against Candida albicans. Results: Lawsone co-crystals exhibited enhanced solubility of lawsone (9.57±2.5 mg/ml and 0.523±0.23 mg/ml respectively) and the particle size of the co-crystals were reduced to 560±2.2 nm as compared to pure lawsone (2478±1.5 nm) which further resulted in enhancement of antifungal activity. Lawsone co-crystals were loaded in the xanthan-gel base for easy applicability to the skin and to achieve patient compliance. The prepared gel was evaluated in terms of spreadability, adhesiveness, in vitro diffusion, viscosity, and antifungal activity. Conclusion: Lawsone co-crystals loaded gel showed enhanced retension of drug in the skin as compared to plain lawsone gel. The antifungal potential of lawsone co-crystals loaded gel was at par with marketed Clotrimazole gel formulation. The short-term stability study carried out as per ICH guideline indicated that the formulation was stable. Lawsone co-crystals loaded gel.

Effects of Juglone on Neutrophil Degranulation and Myeloperoxidase Activity Related to Equine Laminitis

Experimental laminitis, characterized by a failure of the dermal–epidermal interface of the foot, can be induced in horses by the oral administration of a black walnut extract (BWE). In the early phase of this severe and painful disease, an activation of neutrophil occurs, with the release of myeloperoxidase (MPO), a pro-oxidant enzyme of neutrophils, in plasma, skin, and laminar tissue. Juglone, a naphthoquinone derivative endowed with redox properties, is found in walnuts and has been incriminated in this neutrophil activation. We report for the first time the inhibitory activity of juglone on the degranulation of neutrophils induced by cytochalasin B and formyl-methionyl-leucyl-phenylalanine as monitored by the MPO release (>90% inhibition for 25 and 50 μM). Moreover, it also acts on the peroxidase activity of MPO by interacting with the intermediate “π cation radical,” as evidenced by the classical and specific immunological extraction followed by enzymatic detection (SIEFED) assays. These results are confirmed by a docking study showing the perfect positioning of juglone in the MPO enzyme active site and its interaction with one of the amino acids (Arg-239) of MPO apoprotein. By chemiluminescence and electron paramagnetic resonance techniques, we demonstrated that juglone inhibited reactive oxygen species (ROS) and superoxide anion free radical produced from phorbol myristate acetate (PMA)-activated polymorphonuclear neutrophils (PMNs). These results indicate that juglone is not the trigger for equine laminitis, at least if we focus on the modulation of neutrophil activation.

Chemical Constituents of the Whole Plant of Verbena hastata and Their Inhibitory Activity Against the Production of AGEs

Two iridoid glycosides (1 and 2), 3 phenolic glycosides (3–5), 1 flavone glycoside (6), 3 biflavonoids (7–9), 1 flavone (10), 2 triterpenes (11 and 12), 1 sterol (13), and 1 naphthoquinone derivative (14) were isolated from the whole plant of Verbena hastata (Verbenaceae). Compounds 3-13 were isolated from V. hastata for the first time. Compound 14 is undescribed in the literature. Incubation of glyceraldehyde and collagen either with phenolic glycosides (3), (4), or (5) or with biflavonoid (8) inhibited the production of advanced glycation end products, with IC50 values of 6.3, 6.4, 6.2, and 6.8 mM, respectively. Aminoguanidine, which was used as a positive control, had an IC50 value of 10.2 mM.

Naphthoquinone-derivative as a synthetic compound to overcome the antibiotic resistance of methicillin-resistant S. aureus

The treatment of Staphylococcus aureus (S. aureus) infections has become more difficult due to the emergence of multidrug resistance in the bacteria. Here, we report the synthesis of a lawsone (2-hydroxy-1,4-naphthoquinone)-based compound as an antimicrobial agent against methicillin-resistant S. aureus (MRSA). A series of lawsone-derivative compounds were synthesized by means of tuning the lipophilicity of lawsone and screened for minimum inhibitory concentrations against MRSA to identify a candidate compound that possesses a potent antibacterial activity. The identified lawsone-derivative compound exhibited significantly improved drug resistance profiles against MRSA compared to conventional antibiotics. The therapeutic efficacy of the compound was validated using murine models of wound infection as well as non-lethal systemic infection induced by MRSA. Our study further revealed the multifaceted modes of action of the compound, mediated by three distinctive mechanisms: (1) cell membrane damage, (2) chelation of intracellular iron ions, and (3) generation of intracellular reactive oxygen species.