Fighting S. aureus catheter-related infections with sophorolipids: Electing an antiadhesive strategy or a release one?

Staphylococcus aureus medical devices related-infections, such as blood stream catheter are of major concern. Their prevention is compulsory and strategies, not prone to the development of resistance, to prevent S. aureus biofilms on catheter surfaces (e.g. silicone) are needed. In this work two different approaches using sophorolipids were studied to prevent S. aureus biofilm formation on medical grade silicone: i) an antiadhesive strategy through covalent bond of sophorolipids to the surface; ii) and a release strategy using isolated most active sophorolipids. Sophorolipids produced by Starmerella bombicola, were characterized by UHPLC-MS and RMN, purified by automatic flash chromatography and tested for their antimicrobial activity towards S. aureus. Highest antimicrobial activity was observed for C18:0 and C18:1 diacetylated lactonic sophorolipids showing a MIC of 50 µg mL-1. Surface modification with acidic or lactonic sophorolipids when evaluating the anti-adhesive or release strategy, respectively, was confirmed by contact angle, FTIR-ATR and AFM analysis. When using a mixture of acidic sophorolipids covalently bonded to silicone surface as antiadhesive strategy cytocompatible surfaces were obtained and a reduction of 90 % on biofilm formation was observed. Nevertheless, if a release strategy is adopted with purified lactonic sophorolipids a higher effect is achieved. Most promising compound was C18:1 diacateylated lactonic sophorolipid that showed no cellular viability reduction when a concentration of 1.5 mg mL-1 was selected and a reduction on biofilm around 5 log units. Results reinforce the applicability of these antimicrobial biosurfactants on preventing biofilms and disclose that their antimicrobial effect is imperative when comparing to their antiadhesive properties.

Anticancer Triazenes: from Bioprecursors to Hybrid Molecules.

Triazenes are a very useful and diverse class of compounds that have been studied for their potential in the treatment of many tumors including brain tumor, leukemia and melanoma. Novel compounds of this class continue to be developed as either anticancer compounds or even with other therapeutic applications. This review focused on several types of triazenes from the simplest ones like 1,3-dialkyl-3-acyltriazenes to the more complex ones like combi-triazenes with an emphasis on how triazenes have been developed as effective antitumor agents.

Cytotoxic Stilbenes and Derivatives as Promising Antimitotic Leads for Cancer Therapy.

The growing incidence of cancer, the toxic side-effects associated with conventional chemotherapeutic agents and the development of multidrug resistance (MDR) drive the search for novel and more effective drugs with multi-target activity and selectivity towards cancer cells. Stilbenes are a group of naturally occurring phenolic compounds of plant origin derived from the phenylpropanoid pathway that may exist as cis- or trans-isomers. Although the trans-isomer is the more common and stable configuration, resveratrol being a representative compound, cis-stilbenes are potent cytotoxic agents that bind to and inhibit tubulin polymerization, destabilizing microtubules. This review summarizes the chemistry and biological evaluation of cytotoxic stilbenes and their synthetic derivatives as promising antimitotic leads for cancer therapy, focusing on the most potent compounds, the combretastatins. Combretastatins isolated from the South African bushwillow Combretum caffrum are among the most potent antimitotic and vascular disrupting agents (VDAs) of natural origin. Preclinical studies have demonstrated their potent antitumor effects in a wide variety of tumors, both in vitro and in vivo, being currently under evaluation in phase 2 and phase 3 clinical trials for several types of solid tumors. Topics covered herein include synthetic medicinal chemistry, modes of action, structure-activity relationships (SAR), preclinical and clinical studies as VDAs in cancer therapy, either as single agents or in combination with cytotoxic anticancer drugs, antiangiogenic agents, or radiation therapy, and development of appropriate formulations based on nanocarriers (e.g., liposomes, nanoemulsions, polymeric, lipid and ceramic nanoparticles, carbon nanotubes) for improved bioavailability and targeted delivery of combretastatins to the tumor vasculature.