Evaluation of Antimicrobial Activity of New Mastoparan Derivatives Using QSAR and Computational Mutagenesis

Antimicrobial peptides, also called body defense peptides, are used against a wide range of pathogens, such as negative- and positive-gram bacteria, mycobacteria, fungi, viruses, etc. Contrary to antibiotics, antimicrobial peptides do not develop resistance. Their wide antimicrobial spectrum situates them as important and attractive targets in research and pharmaceutical industry in order to obtain new structures using modern drug design techniques. We present here eleven QSAR models in which antimicrobial activity expressed as minimal inhibitory concentration values at Bacillus subtilis of 37 mastoparan analogs was correlated with different physicochemical parameters like: number of hydrophobic centers, molecular area and volume, internal dipole moment, refractivity, RPCG (relative positive charges) and number of donor and acceptor atoms generating by use of the computational software Sybyl. Significant R 2 (0.68-0.72) correlation coefficients and standard error of prediction SEE (0.199-0.230) were obtained, indicating that the established equations can be used. Thus, these linear models allowed us to create a library of 19 derivatives of mastoparan analogs obtained through computational mutagenesis. We propose this library of compounds as a source of possible derivatives with a more potent antimicrobial activity

Designing of artificial peptides for an improved antiviral activity

© 2018 Bentham Science PublishersBackground: Few HIV-1fusion and replication inhibitors were developed, with limited clinical applications because of their short half-life, drug resistance and cross-reactivity with preexisting antibodies in HIV-infected patients. Objective: These limitations call for new strategies in the development of next anti-HIV-1 drugs. Among anti-gp41HIV-1 inhibitors, short-peptides exhibit high antiviral activity but the mechanism of action at molecular level has not been sufficiently addressed. Method: We report potent QSAR (Quantitative Structure-Activity Relationship) models, used for biological activity prediction of novel short HIV-1 gp41 inhibitor peptides in order to: (i) validate the anti-HIV-1 activity of MT-sifuvirtide, MT-SC34EK, MT-C34 and HP23, expressed as IC50fusion and IC50replication; (ii) predict inhibitory activity of SC24EK and its MT-derivative expressed as IC50resistant HIV-1 NL4-3 variant; (iii) propose new derivatives DMT-SC22EK, DMT-SC29EK and DMT-sifuvirtide through addition of aspartic acids by induced-mutagenesis; (iv) use molecular similarity established by fingerprint models to correlate molecular spatial features with predicted biological activity of newly generated inhibitors over parent compounds. Results: We obtained good QSAR statistic parameters, demonstrating that our QSAR models are able to predict biological activity of new HIV-1 inhibitors with suitable accuracy. Conclusion: Despite acknowledged drawbacks of a reduced dataset, our results may enhance the evaluation of biological activity of new and classical synthetic peptides as anti-HIV-1agents and represent a good start for further studies in developing new antiviral drugs.info:eu-repo/semantics/publishedVersio

Zinc Oxide Nanoparticles Induces Apoptosis in Human Breast Cancer Cells via Caspase-8 and P53 Pathway

Nanoparticles are a special institution of substances with precise capabilities and significant applications in many biomedical fields. In the present work zinc oxide nanoparticles were prepared through sol-gel approach. The synthesised nanoparticles were identified through the usage of X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In-vitro anticancer activity of zinc oxide nanoparticles towards MCF-7 cell lines using numerous parameters was investigated. Zinc oxide nanoparticles were determined to exert cell growth arrest against MCF-7 cell lines. The anti-proliferative efficiency of ZnO nanoparticles was due to cell dying and inducing apoptosis that were confirmed by the usage of acridine orange/ethidium bromide dual staining, DAPI staining and genotoxicity assay. Reverse transcription polymerase chain reaction (RT- PCR) analysis achieved to identify the gene expression of Caspase-8, Caspase-9, and P53. The results suggested that ZnO nanoparticles might find a wide use in clinical applications and provide new drug recompense for chemotherapy drugs

Efficiency of Vanilla, Patchouli and Ylang Ylang Essential Oils Stabilized by Iron Oxide@C14 Nanostructures against Bacterial Adherence and Biofilms Formed by Staphylococcus aureus and Klebsiella pneumoniae Clinical Strains

Biofilms formed by bacterial cells are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence and chronicization of the microbial infections and to therapy failure. The purpose of this study was to combine the unique properties of magnetic nanoparticles with the antimicrobial activity of three essential oils to obtain novel nanobiosystems that could be used as coatings for catheter pieces with an improved resistance to Staphylococcus aureus and Klebsiella pneumoniae clinical strains adherence and biofilm development. The essential oils of ylang ylang, patchouli and vanilla were stabilized by the interaction with iron oxide@C14 nanoparticles to be further used as coating agents for medical surfaces. Iron oxide@C14 was prepared by co-precipitation of Fe+2 and Fe+3 and myristic acid (C14) in basic medium. Vanilla essential oil loaded nanoparticles pelliculised on the catheter samples surface strongly inhibited both the initial adherence of S. aureus cells (quantified at 24 h) and the development of the mature biofilm quantified at 48 h. Patchouli and ylang-ylang essential oils inhibited mostly the initial adherence phase of S. aureus biofilm development. In the case of K. pneumoniae, all tested nanosystems exhibited similar efficiency, being active mostly against the adherence K. pneumoniae cells to the tested catheter specimens. The new nanobiosystems based on vanilla, patchouli and ylang-ylang essential oils could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with anti-adherence and anti-biofilm properties