Synthesis and Biological Studies of New Temporin A Analogs Containing Unnatural Amino Acids in Position 7.

(1) Background: Antimicrobial resistance is growing at an extreme pace and has proven to be an urgent topic, for research into alternative treatments. Such a prospective possibility is hidden in antimicrobial peptides because of their low to no toxicity, effectiveness at low concentrations, and most importantly their ability to be used for multiple treatments. This work was focused on the study of the effect of the modification in position 7 of Temporin A on its biological activity; (2) Methods: The targeted peptides were synthesized using Fmoc/Ot-Bu SPPS. The antibacterial activity of the analogs was determined using the broth microdilution method and disk-diffusion method. In vitro tests were performed to determine the cytotoxicity, phototoxicity, and antiproliferative activity of the peptide analogs on a panel of tumor and normal cell lines; (3) Results: All analogs except DTCit showed good antibacterial activity, with DTDab having the best activity according to the disk-diffusion method. However, DTCit had an acceptable cytotoxicity, combined with good selectivity against the test MCF-7 cell line; (4) Conclusions: The obtained results revealed the importance of the basicity and length of the side chain at position 7 in the Temporin A sequence for both tested activities.

Effect of B2O3 on the Structure, Properties and Antibacterial Abilities of Sol-Gel-Derived TiO2/TeO2/B2O3 Powders.

This paper studies the influence of B2O3 on the structure, properties and antibacterial abilities of sol-gel-derived TiO2/TeO2/B2O3 powders. Titanium(IV) butoxide, telluric(VI) acid and boric acid were used as precursors. Differences were observed in the degree of decomposition of Ti butoxide in the presence of H3BO3 and H6TeO6 acids. The phase transformations of the obtained gels in the temperature range of 200-700 °C were investigated by XRD. Composite materials containing an amorphous phase and different crystalline phases (metallic Te, α-TeO2, anatase, rutile and TiTe3O8) were prepared. Heating at 400 °C indicated a crystalline-to-amorphous-phase ratio of approximately 3:1. The scanning electron microscopy (SEM) analysis showed the preparation of plate-like TiO2 nanoparticles. The IR results showed that the short-range order of the amorphous phases that are part of the composite materials consists of TiO6, BO3, BO4 and TeO4 structural units. Free B2O3 was not detected in the investigated compositions which could be related to the better connectivity between the building units as compared to binary TiO2/B2O3 compositions. The UV-Vis spectra of the investigated gels exhibited a red shift of the cut-off due to the presence of boron and tellurium units. The binary sample achieved the maximum photodegradation efficiency (94%) toward Malachite green dye under UV irradiation, whereas the ternary sample photoactivity was very low. The compositions exhibited promising antibacterial activity against E. coli NBIMCC K12 407.

Synthesis, Anticancer Activity, Docking Calculations and Hydrolytic Stability Studies of Bioconjugates of Monofluorenated Analogue of BIM- 23052.

BACKGROUND: The fight against cancer has started since its discovery and has not subsided to nowadays. Currently, the hybrid molecules have become a promising alternative to the standard chemotherapeutics for the treatment of multi-causal diseases, including cancers. OBJECTIVE: Herein, we report the synthesis, biological evaluation, mathematical docking calculations and hydrolytic stability of the new bioconjugates of monofluorinated analogues of BIM-23052, containing second pharmacophore naphthalimide, caffeic acid or the tripeptide Arg-Gly-Asp. METHODS: All new molecules are obtained using standard peptide synthesis on solid support. Anticancer potential is studied against a panel of tumor cell lines included human mammary carcinoma cell lines MCF-7 (ER+, PR+ and Her-2-); MDA-MB-231 (ER-, PR- and Her-2-), as well as cell lines BALB 3T3 (mouse embryonic fibroblasts) and MCF-10A (human breast epithelial cell line). RESULTS: The IC50 values found in the MCF-10A cell line assay were used to calculate the selective index (SI). The highest SI relative to MCF-7, with a value of 2.62 is shown by the compound Npht- Gly-D-Phe-Phe(4-F)-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2. In MCF-10 cells, the weakest antiproliferative effect was caused by the same compound (IC50 = 622.9 ± 23.91 µM), which makes this analogue a good candidate for the new anticancer medical drug. Unfortunately, the hydrolytic stability studies reveal that this bioconjugate is the most unstable of hydrolysis under physiological conditions in the body. CONCLUSION: Even with lower anticancer activity and selectivity in comparison with Npht-Gly-DPhe- Phe(4-F)-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2, the compound Arg-Gly-Asp-D-Phe-Phe(4-F)-Phe- D-Trp-Lys-Thr-Phe-Thr-NH2 is the best candidate between three investigated bioconjugates for practical application due to combination of activity and stability profiles. Mathematical docking calculation also reveals that synthesized bioconjugates show selectivity according to different somatostatin receptors on the surface of different cell lines.

Synthesis and Biological Studies on (KLAKLAK)2-NH2 Analog Containing Unnatural Amino Acid ß-Ala and Conjugates with Second Pharmacophore.

(1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)2 is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)2-NH2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)2-NH2 and Caf-(KLAKLAK)2-NH2. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLß-AKLß-AK)2-NH2 containing ß-Ala in its structures exhibited good antimicrobial activity against Escherichia coli K12 407 and Bacillus subtilis 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents.