Activity In Presence Of Serum Research Articles

Antimicrobial activity of an artificially designed peptide against fish pathogens

Antimicrobial peptides (AMPs) are considered alternatives to classical antibiotics and may become an excellent candidate for tackling antimicrobial resistance in aquaculture. Designing novel antimicrobial peptides for curbing antimicrobial resistance in aquaculture is paramount in one health approach. In this study, a short and compositionally simple peptide, KK16, was designed. KK16 is amphipathic with a net charge of + 6. Molecular docking results revealed that KK16 has a strong affinity towards two virulence proteins of Aeromonas sobria; aerolysin and outer membrane protein (omp). The peptide was synthesised using Fmoc-chemistry, and its antimicrobial efficacy was evaluated in vitro against A.sobria, A. salmonicida, Edwardsiella tarda, A. hydrophila, Vibrio parahaemolyticus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis and methicillin-resistant S. aureus. The KK16 AMP showed potent activity against the tested bacterial pathogens as revealed by the MIC and MBC, ranging from 7.81 to 500 µM, and 15–900 µM, respectively. Moreover, the peptide was stable at higher temperatures and retained its activity in presence of serum and salt. The peptide displayed less haemolytic and cytotoxic activity even at higher concentrations. In peptide-DNA binding assay, KK16 showed its binding potential with bacterial genomic DNA and thus, may interfere with replication. Fluorescent microscopy revealed the uptake of propidium iodide by peptide treated bacterial cells, indicating its membrane disruption activity. In in vivo experiment, KK16 peptide completely inhibited the growth of Saprolegnia parasitica fungus at ≥ 30 µM peptide concentrations in embryonated fish eggs. The results indicate that KK16 peptide is stable, possess potent antibacterial and antifungal activity, less cytotoxic to host cells, and hence may prove to be a promising anti-infective agent for combating common bacterial and fungal infections.

Rhodanine derivatives as potent anti-HIV and anti-HSV microbicides.

Although highly active antiretroviral therapies (HAART) remarkably increased life expectancy of HIV positive people, the rate of novel HIV-1 infections worldwide still represent a major concern. In this context, pre-exposure prophylaxis (PrEP) approaches such as vaginal microbicide gels topically releasing antiretroviral drugs, showed to have a striking impact in limiting HIV-1 spread. Nevertheless, the co-presence of other genital infections, particularly those due to HSV-1 or 2, constitute a serious drawback that strongly limits the efficacy of PrEP approaches. For this reason, combinations of different compounds with mixed antiviral and antiretroviral activity are thoroughly investigated Here we report the synthesis and the biological evaluation of a novel series of rhodanine derivatives, which showed to inhibit both HIV-1 and HSV-1/2 replication at nanomolar concentration, and were found to be active also on acyclovir resistant HSV-2 strains. The compounds showed a considerable reduction of activity in presence of serum due to a high binding to serum albumin, as determined through in vitro ADME evaluations. However, the most promising compound of the series maintained a considerable activity in gel formulation, with an EC50 comparable to that obtained for the reference drug tenofovir. Moreover, the series of compounds showed pharmacokinetic properties suitable for topical formulation, thus suggesting that the novel rhodanine derivatives could represent effective agents to be used as dual anti HIV/HSV microbicides in PrEP approaches.