initiate apoptosis in target cells, though its action was slower than that of the native ChBac3.4. Its antitumor effectiveness was successfully verified in vivo in a murine Ehrlich ascites carcinoma model. The obtained results demonstrate the potential of structural modification to manage caprine bactenecins' selectivity and activity spectrum and confirm that they are promising prototypes for antimicrobial and anticancer drugs design.

No abstract

Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics are one of the common components for topical treatment potent against antibiotic-resistant pathogens but often with toxicity limitations of their own. Thus, the interaction of AMPs and antiseptics is an interesting topic that is also less explored than combined action of AMPs and antibiotics. Herein, we analyzed antibacterial, antibiofilm, and cytotoxic activity of combinations of both membranolytic and non-membranolytic AMPs with a number of antiseptic agents. Fractional concentration indices were used as a measure of possible effective concentration reduction achievable due to combined application. Cases of both synergistic and antagonistic interaction with certain antiseptics and surfactants were identified, and trends in the occurrence of these types of interaction were discussed. The data may be of use for AMP-based drug development and suggest that the topic requires further attention for successfully integrating AMPs-based products in the context of complex treatment. AMP/antiseptic combinations show promise for creating topical formulations with improved activity, lowered toxicity, and, presumably, decreased chances of inducing bacterial resistance. However, careful assessment is required to avoid AMP neutralization by certain antiseptic classes in either complex drug design or AMP application alongside other therapeutics/care products.

Saliva is an important biological fluid that reflects human’s health. Its main function is protection of the oral cavity from pathogens. Antimicrobial peptides (AMPs) of the innate immunity may play an important role in anti-infectious defense of the oral cavity, but their relative amount in saliva is low. It’s major component is Proline-rich peptides (PRPs), whose impact in antimicrobial protection remains poorly understood. We suggest that salivary PRPs may reveal their defensive functions upon interaction with other molecules, in particular with AMPs. The aim of this work is an investigation of the combined antibacterial action of salivary PRPs (fragments of Basic salivary proline-rich protein 1: P-H (37-51), IB6 (98-116), p1932) with antimicrobial peptides (histatin 5 and cathelicidin LL-37 and beta-defensin hBD3). Listed PRPs have been obtained by chemical solid-phase synthesis. The method of broth microdilutions was used to compare minimal inhibitory concentrations (MICs) of individual fractions of AMPs and their MICs in the presence of salivary peptides. It was found that in the presence of peptides IB6 (98-116) or P-H (37-51) the activity of defensin hBD3 was increased (reduction of MICs by 2 times) against Staphylococcus aureus SG511. In the presence of IB6 (98-116) or p1932 the activity of this defensin against E. coli ML35p was also improved (MICs of hBD3 was lowered by 2 times). For other combinations of the peptides, this effect was not observed. The obtained data confirm the assumption that the combined action of varied salivary peptides, including cationic Proline-rich peptides, plays an important role in anti-infectious protection of the oral cavity.