Synthesis, Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)2-NH2 and Their Conjugates Containing Unnatural Amino Acids.

(1) Background: (KLAKLAK)2 is a representative of the antimicrobial peptide group which also shows good anticancer properties. (2) Methods: Herein, we report synthesis using SPPS and characterization by HPLC/MS of a series of shortened analogues of (KLAKLAK)2. They contain single sequence KLAKLAK as C-terminal amides. In addition, substitution of some natural amino acids with unnatural ß-Ala and nor-Leu is realized. In addition, these structures are conjugated with second pharmacophore with well proven anticancer properties 1,8-naphthalimide or caffeic acid. Cytotoxicity, antiproliferative effect and antimicrobial activity of newly synthesized structures were studied. (3) Results: The obtained experimental results reveal significant selective index for substances with common chemical structure KLßAKLßAK-NH2. The antibacterial properties of newly synthesized analogues at two different concentrations 10 µM and 20 µM, were tested against Gram-negative microorganisms Escherichia coli K12 407. Only two of the studied compounds KLAKLAK-NH2 and the one conjugated with second pharmacophore 1,8-naphthalimide and unnatural amino acid nor-Leu showed moderate activity against tested strains at concentration of 20 µM. (4) Conclusions: The obtained results reveal that the introducing of 1,8-naphthalimideGly- and Caf- increase the cytotoxicity and antiproliferative activity of the peptides but not their selectivity. Only two compounds KLAKLAK-NH2 and 1,8-naphthalimideGKnLAKnLAK-NH2 show moderate activity against Escherichia coli K12 at low concentration of 20µM.

Study of potential biomedical application of sol-gel derived Zn-doped SiO2-hydroxypropyl cellulose nanohybrids.

A series of Zn-doped hybrid materials based on silica from tetraethoxysilane (TEOS) and hydroxypropyl cellulose (HPC) were prepared by a sol-gel route. The structure, morphology and thermal behavior of synthesized hybrids were characterized by infrared (IR) spectroscopy, ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM) and differential thermal analysis with thermogravimetric analysis (DTA/TG). The obtained materials were investigated for a potential biomedical application. The antibacterial properties of hybrids were investigated by measuring the inhibition zones formed around the materials containing different zinc content in presence of reference strains of Gram-positive and Gram-negative bacteria. The biocompatibility tests showed no cytotoxicity and genotoxicity, as well as no changes in actin cytoskeleton organization for hybrids with Zn content below 5 wt%.

Synthesis, characterization and antibacterial assessment of SiO2-hydroxypropylmethyl cellulose hybrid materials with embedded silver nanoparticles.

Antibacterial SiO2 hybrid materials based on tetraethyl orthosilicate (TEOS), hydroxypropylmethylcellulose (HPMC) and silver were prepared by the sol-gel method. The content of cellulose derivate was 5 wt% and the silver concentration varied from 0.5 wt% to 2.5 wt%. The amorphous nature, morphology and antibacterial behaviour were studied. Fourier transform infrared (FTIR) spectra of the hybrids showed characteristic peaks for SiO2 network. Scanning electron microscope (SEM) analysis confirmed the formation of spherically shaped silver nanoparticles with a size of 30 nm on the matrix surfaces. Bacillus subtilis and Escherichia coli K12 were used as model microorganisms. The hybrid materials demonstrated bacteriostatic and bactericidal effect on the tested bacteria. Highest sensitivity to the obtained hybrids was observed in B. subtilis with significant lag-phase delay and biggest inhibition zone sizes.

Preparation and characterization of SiO2/CMC/Ag hybrids with antibacterial properties.

Amorphous hybrids based on sodium salt of carboxymethyl cellulose (CMC) and tetraethoxysilane (TEOS) containing silver nanoparticles were prepared by sol-gel method. The amorphous structure, morphology and antibacterial behavior were clarified. The thermal stability of obtained hybrids decreased with the increase in silver content from 0.5 to 1.5 wt%. Infrared spectra of the material suggest that the main interaction between the cellulose ether and silica network is via hydrogen bonds (bands at approximately 3,540 and 3,625 cm(-1)). According to UV-vis spectra the silver is present in two different states Ag(+) (absorption band at approximately 210 nm) and Ag(0) (band at approximately 300 nm). The different sizes of silver particles are present as clusters. It was demonstrated that these hybrids have a well pronounced antibacterial activity against B. subtilis and E. coli K12. Even the hybrid with 0.5 wt% Ag has efficient antibacterial activity for both Gram-positive and Gram-negative bacteria.