In silico and in vitro structure-stability-function relationship of analog peptides of Stigmurin and its antibacterial and antibiofilm activities.

Multidrug-resistant bacterial infections are a threat to public health worldwide, which boosts the urgent need for pharmacological research for new drugs. Although the peptides without disulfide bridges from scorpions have shown antimicrobial action, usually their toxicity hamper their pharmacological application. Stigmurin is a non-hemolytic cationic peptide from Tityus stigmurus venom with antibacterial effect and toxicity on normal cells. In this approach, the conformational changes and stability of two Stigmurin analog peptides, named StigA8 and StigA18, were evaluated by circular dichroism, as well as the mechanism of interaction with bacterial membranes in silico. In addition, the in vitro and in vivo antibacterial activity and the action against the biofilm formed by multidrug-resistant Staphylococcus aureus were investigated. StigA8 (+4) and StigA18 (+5) revealed the ability to change their structural conformation depending on the medium composition, and high stability at different temperatures and pH conditions. Both analog peptides showed greater ability to interact with bacterial membranes in silico when compared to the native one. StigA8 and StigA18 demonstrated low hemolytic action, with non-toxic effect on G. mellonella larvae up to 120 mg/kg. StigA8 and StigA18 presented a broad spectrum of antibacterial action in vitro, especially against multidrug-resistant clinical isolates. The analog peptides (7.5 µM) also reduced the biofilm biomass of multidrug-resistant S. aureus, as well as increased the larval survival of the Galleria mellonella infected larvae. Therefore, StigA8 and StigA18 showed a beneficial potential in the treatment of bacterial infections, constituting promising bioactive components for the development of new antimicrobial agents.

Chemical composition, antioxidant and topical antiinflammatory activities of Croton cordiifolius Baill. (Euphorbiaceae)

Croton cordiifolius is widely used in Brazilian Caatinga folk medicine to treat general inflammation, pain, and gastrointestinal disturbances. Currently, its medicinal properties are not well understood, owing to the absence of chemical and pharmacological studies. The aims of this work were to analyze the chemical composition of C. cordiifolius stem bark and evaluate its in vitro antioxidant and in vivo anti-inflammatory activities. C. cordiifolius ethanolic extract (CcEE) was obtained by maceration, while essential oil (CcEO) was extracted by hydrodistillation in a Clevenger-type apparatus. The chemical composition was evaluated by thin-layer chromatography and GCMS. Total phenolics, flavonoids, and antioxidant activity were quantitated by spectrophotometry. Topical anti-inflammatory activity was evaluated by different ear edema models in mice. The major compounds in CcEO were α-pinene (51.76%) and ß-pinene (19.08%). CcEE analysis indicated the presence of alkaloids, mono- and sesquiterpenes, flavonoids, phenylpropanoids, triterpenes, steroids, and coumarins. CcEE showed antioxidant activity in vitro. In a topical anti-inflammatory assay, CcEO showed no activity. On the contrary, CcEE inhibited ear edema induced by phorbol 12-myristate 13-acetate (PMA), arachidonic acid (AA), ethyl phenylpropriolate (EPP), and phenol. Probable mechanisms include inhibition of AA metabolite biosynthesis, vasoactive amine activity, and cytokine release/activity. These results corroborate the popular reputation of C. cordiifolius as an anti-inflammatory remedy.(AU)