In Silico and In Vitro Experimental Studies of New Dibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents

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 i...

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Main Authors:	Ilinca Margareta Vlad, Diana Camelia Nuta, Cornel Chirita, Miron Teodor Caproiu, Constantin Draghici, Florea Dumitrascu, Coralia Bleotu, Speranța Avram, Ana Maria Udrea, Alexandru Vasile Missir, Luminita Gabriela Marutescu, Carmen Limban
Format:	Article
Language:	English
Published:	MDPI AG 2020-01-01
Series:	Molecules
Subjects:	dibenz[<i>b</i>,<i>e</i>]oxepins oxime carbamates antibacterial antifungal antibiofilm in silico in vitro cytotoxicity
Online Access:	https://www.mdpi.com/1420-3049/25/2/321

id	doaj-320640d2e3c24adfbcd47e7d7f47b473
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collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ilinca Margareta Vlad Diana Camelia Nuta Cornel Chirita Miron Teodor Caproiu Constantin Draghici Florea Dumitrascu Coralia Bleotu Speranța Avram Ana Maria Udrea Alexandru Vasile Missir Luminita Gabriela Marutescu Carmen Limban
spellingShingle	Ilinca Margareta Vlad Diana Camelia Nuta Cornel Chirita Miron Teodor Caproiu Constantin Draghici Florea Dumitrascu Coralia Bleotu Speranța Avram Ana Maria Udrea Alexandru Vasile Missir Luminita Gabriela Marutescu Carmen Limban In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents Molecules dibenz[<i>b</i>,<i>e</i>]oxepins oxime carbamates antibacterial antifungal antibiofilm in silico in vitro cytotoxicity
author_facet	Ilinca Margareta Vlad Diana Camelia Nuta Cornel Chirita Miron Teodor Caproiu Constantin Draghici Florea Dumitrascu Coralia Bleotu Speranța Avram Ana Maria Udrea Alexandru Vasile Missir Luminita Gabriela Marutescu Carmen Limban
author_sort	Ilinca Margareta Vlad
title	In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents
title_short	In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents
title_full	In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents
title_fullStr	In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents
title_full_unstemmed	In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents
title_sort	in silico and in vitro experimental studies of new dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>h</i>)one o-(arylcarbamoyl)-oximes designed as potential antimicrobial agents
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2020-01-01
description	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[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)oximes. The structures of intermediary and final substances (compounds <b>7a</b>−<b>j</b>) were confirmed by <sup>1</sup>H-NMR, <sup>13</sup>C-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 <b>7a</b>−<b>j</b>, 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 <i>Staphylococcus aureus</i> and <i>Bacillus subtilis</i> strains and the <i>Candida albicans</i> fungal strain. The obtained compounds also inhibited the ability of <i>S. aureus</i>, <i>B. subtilis</i>, <i>Escherichia coli</i> and <i>C. albicans</i> 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.
topic	dibenz[<i>b</i>,<i>e</i>]oxepins oxime carbamates antibacterial antifungal antibiofilm in silico in vitro cytotoxicity
url	https://www.mdpi.com/1420-3049/25/2/321
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spelling	doaj-320640d2e3c24adfbcd47e7d7f47b4732020-11-25T02:20:25ZengMDPI AGMolecules1420-30492020-01-0125232110.3390/molecules25020321molecules25020321In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial AgentsIlinca Margareta Vlad0Diana Camelia Nuta1Cornel Chirita2Miron Teodor Caproiu3Constantin Draghici4Florea Dumitrascu5Coralia Bleotu6Speranța Avram7Ana Maria Udrea8Alexandru Vasile Missir9Luminita Gabriela Marutescu10Carmen Limban11Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, sect. 2, 020956 Bucharest, RomaniaDepartment of Pharmaceutical Chemistry, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, sect. 2, 020956 Bucharest, RomaniaDepartment of Pharmacology and Clinical Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, sect. 2, 020956 Bucharest, RomaniaThe Organic Chemistry Center of Romanian Academy “Costin D. Nenitescu”, Splaiul Independenței 202B, 77208 Bucharest, RomaniaThe Organic Chemistry Center of Romanian Academy “Costin D. Nenitescu”, Splaiul Independenței 202B, 77208 Bucharest, RomaniaThe Organic Chemistry Center of Romanian Academy “Costin D. Nenitescu”, Splaiul Independenței 202B, 77208 Bucharest, RomaniaȘtefan S Nicolau Institute of Virology, Romanian Academy, 285 Mihai Bravu Avenue, 030304 Bucharest, RomaniaDepartment of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 1-3 Ale. Portocalelor, 060101 Bucharest, RomaniaDepartment of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 1-3 Ale. Portocalelor, 060101 Bucharest, RomaniaDepartment of Pharmaceutical Chemistry, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, sect. 2, 020956 Bucharest, RomaniaResearch Institute of the University of Bucharest (ICUB) and Microbiology Immunology Department, Faculty of Biology, University of Bucharest, 1-3 Ale. Portocalelor, 060101 Bucharest, RomaniaDepartment of Pharmaceutical Chemistry, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia 6, sect. 2, 020956 Bucharest, RomaniaIn 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[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)oximes. The structures of intermediary and final substances (compounds <b>7a</b>−<b>j</b>) were confirmed by <sup>1</sup>H-NMR, <sup>13</sup>C-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 <b>7a</b>−<b>j</b>, 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 <i>Staphylococcus aureus</i> and <i>Bacillus subtilis</i> strains and the <i>Candida albicans</i> fungal strain. The obtained compounds also inhibited the ability of <i>S. aureus</i>, <i>B. subtilis</i>, <i>Escherichia coli</i> and <i>C. albicans</i> 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.https://www.mdpi.com/1420-3049/25/2/321dibenz[<i>b</i>,<i>e</i>]oxepinsoxime carbamatesantibacterialantifungalantibiofilmin silicoin vitro cytotoxicity

In Silico and In Vitro Experimental Studies of New Dibenz[<i>b</i>,<i>e</i>]oxepin-11(6<i>H</i>)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents

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