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Design, Synthesis and In Vitro Characterization of Novel Antimicrobial Agents Based on 6-Chloro-9H-carbazol Derivatives and 1,3,4-Oxadiazole Scaffolds
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In Silico and In Vitro Experimental Studies of New Dibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents

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Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, sect. 2, 020956 Bucharest, Romania
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Department of Pharmacology and Clinical Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, sect. 2, 020956 Bucharest, Romania
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The Organic Chemistry Center of Romanian Academy “Costin D. Nenitescu”, Splaiul Independenței 202B, 77208 Bucharest, Romania
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Ștefan S Nicolau Institute of Virology, Romanian Academy, 285 Mihai Bravu Avenue, 030304 Bucharest, Romania
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Research Institute of the University of Bucharest (ICUB) and Microbiology Immunology Department, Faculty of Biology, University of Bucharest, 1-3 Ale. Portocalelor, 060101 Bucharest, Romania
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Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 1-3 Ale. Portocalelor, 060101 Bucharest, Romania
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Laser Department, National Institute for Laser, Plasma and Radiation Physics, Atomistilor Street 409, 077125 Magurele, Romania
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Author to whom correspondence should be addressed.
Molecules 2020, 25(2), 321; https://doi.org/10.3390/molecules25020321
Received: 16 November 2019 / Revised: 24 December 2019 / Accepted: 6 January 2020 / Published: 13 January 2020
(This article belongs to the Special Issue Synthetic Antibiofilm Agents: Design, Synthesis and Applications)
In a drug-repurposing-driven approach for speeding up the development of novel antimicrobial agents, this paper presents for the first time in the scientific literature the synthesis, physico-chemical characterization, in silico analysis, antimicrobial activity against bacterial and fungal strains in planktonic and biofilm growth state, as well as the in vitro cytotoxicity of some new 6,11-dihydrodibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)oximes. The structures of intermediary and final substances (compounds 7aj) were confirmed by 1H-NMR, 13C-NMR and IR spectra, as well as by elemental analysis. The in silico bioinformatic and cheminformatic studies evidenced an optimal pharmacokinetic profile for the synthesized compounds 7aj, characterized by an average lipophilic character predicting good cell membrane permeability and intestinal absorption; low maximum tolerated dose for humans; potassium channels encoded by the hERG I and II genes as potential targets and no carcinogenic effects. The obtained compounds exhibited a higher antimicrobial activity against the planktonic Gram-positive Staphylococcus aureus and Bacillus subtilis strains and the Candida albicans fungal strain. The obtained compounds also inhibited the ability of S. aureus, B. subtilis, Escherichia coli and C. albicans strains to colonize the inert substratum, accounting for their possible use as antibiofilm agents. All the active compounds exhibited low or acceptable cytotoxicity levels on the HCT8 cells, ensuring the potential use of these compounds for the development of new antimicrobial drugs with minimal side effects on the human cells and tissues. View Full-Text
Keywords: dibenz[b,e]oxepins; oxime carbamates; antibacterial; antifungal; antibiofilm; in silico; in vitro cytotoxicity dibenz[b,e]oxepins; oxime carbamates; antibacterial; antifungal; antibiofilm; in silico; in vitro cytotoxicity
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Vlad, I.M.; Nuta, D.C.; Chirita, C.; Caproiu, M.T.; Draghici, C.; Dumitrascu, F.; Bleotu, C.; Avram, S.; Udrea, A.M.; Missir, A.V.; Marutescu, L.G.; Limban, C. In Silico and In Vitro Experimental Studies of New Dibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents. Molecules 2020, 25, 321.

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