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      α-Amidoamids as New Replacements of Antibiotics—Research on the Chosen K12, R2–R4 E. coli Strains

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          Abstract

          A preliminary study of α-amidoamids as new potential antimicrobial drugs was performed. Special emphasis was placed on selection of structure of α-amidoamids with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R1–R4 (with different length LPS in its structure) were used. The presented work showed that the antibacterial activity of α-amidoamids depends on their structure and affects the LPS of bacteria. Moreover, the influence of various newly synthesized α-amidoamids on bacteria possessing smooth and rought LPS and oxidative damage of plasmid DNA caused by all newly obtained compounds was indicated. The presented studies clearly explain that α-amidoamids can be used as substitutes for antibiotics. The chemical and biological activity of the analysed α-amidoamids was associated with short alkyl chain and different isocyanides molecules in their structure such as: tetr-butyl isocyanide or 2,5-dimethoxybenzyl isocyanide. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.

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          Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

          Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.
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            Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer

            Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer.
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              How antibiotics kill bacteria: from targets to networks.

              Antibiotic drug-target interactions, and their respective direct effects, are generally well characterized. By contrast, the bacterial responses to antibiotic drug treatments that contribute to cell death are not as well understood and have proven to be complex as they involve many genetic and biochemical pathways. In this Review, we discuss the multilayered effects of drug-target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing. We also discuss new insights into these mechanisms that have been revealed through the study of biological networks, and describe how these insights, together with related developments in synthetic biology, could be exploited to create new antibacterial therapies.
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                Author and article information

                Journal
                Materials (Basel)
                Materials (Basel)
                materials
                Materials
                MDPI
                1996-1944
                16 November 2020
                November 2020
                : 13
                : 22
                : 5169
                Affiliations
                [1 ]Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland
                [2 ]Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland; arleta.madej@ 123456icho.edu.pl
                [3 ]Department of Molecular Virology, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland; mszymczak@ 123456biol.uw.edu.pl
                Author notes
                Author information
                https://orcid.org/0000-0003-4025-3750
                https://orcid.org/0000-0003-4056-7792
                https://orcid.org/0000-0002-3032-196X
                Article
                materials-13-05169
                10.3390/ma13225169
                7697494
                33207799
                ae51e7c0-8354-4d85-b383-aa157baff15c
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 October 2020
                : 12 November 2020
                Categories
                Article

                oxidative stress,ugi reaction,peptidomimetics,fpg-n-glycosylase/ap lyase dna,lps—lipopolysaccharide,alpha-amidoamides (aaas)

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