JavaScript is required...

Please enable Javascript in order to use PubChem website.

Are you interested in learning more about 9-fluorenone molecular weight? Contact us today to secure an expert consultation!

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 ( https://creativecommons.org/licenses/by/4.0/ ).

Antimicrobial resistance is one of the major public health threats at the global level, urging the search for new antimicrobial molecules. The fluorene nucleus is a component of different bioactive compounds, exhibiting diverse pharmacological actions. The present work describes the synthesis, chemical structure elucidation, and bioactivity of new O-aryl-carbamoyl-oxymino-fluorene derivatives and the contribution of iron oxide nanoparticles to enhance the desired biological activity. The antimicrobial activity assessed against three bacterial and fungal strains, in suspension and biofilm growth state, using a quantitative assay, revealed that the nature of substituents on the aryl moiety are determinant for both the spectrum and intensity of the inhibitory effect. The electron-withdrawing inductive effect of chlorine atoms enhanced the activity against planktonic and adhered Staphylococcus aureus, while the +I effect of the methyl group enhanced the anti-fungal activity against Candida albicans strain. The magnetite nanoparticles have substantially improved the antimicrobial activity of the new compounds against planktonic microorganisms. The obtained compounds, as well as the magnetic core@shell nanostructures loaded with these compounds have a promising potential for the development of novel antimicrobial strategies.

1. Introduction

Antimicrobial resistance represents one of the major threats to public health worldwide, causing 700,000 deaths annually, and the number is expected to rise to 10 million in 2050. The dramatic decrease in the effectiveness of the currently available treatments is urging the immediate discovery of novel antibiotics [1]. However, the interest of pharmaceutical industry seems to remain low in investing in the field of antibiotics [2], needing to be counterbalanced by a stronger commitment of the academic researchers for the development of novel antimicrobial strategies.

Fluorene, a tricyclic aromatic hydrocarbon, is found in the structure of some drugs, such as lumefantrine (antimalarial), imirestat (aldozreductase inhibitor), cicloprofen (analgesic, anti-inflammatory agent), pavatrin (antispasmodic), indecainide (antiarrhythmic), and hexafluronium bromide (muscle relaxant, a nicotinic acetylcholine receptor antagonist) ( ).

A number of new fluorene derivatives were obtained using as the basic intermediate N-octadecyl-9-oxo-9H-fluoren-4-carboxamide. The synthesized derivatives react with propylene oxide, resulting in compounds with good surface-active properties. Therefore, these compounds can be used in different applications as drugs, wetting agents, moderate emulsifiers, household detergents, paints, and also in the cosmetic and textile industry [3]. The biological degradation of fluorene-based surfactants was more than 96% after seven days. Most of the compounds exhibited variable inhibitory effects on Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, Escherichia coli) bacterial strains, as well as on fungal strains (Aspergillus niger, Candida albicans and Curvularia spp.).

2-(9H-fluorene-2-yl)-3-phenyl-bicyclo[2.2.1]hept-5-ene-2-yl methanone derivatives, which have the phenyl radical substituted by various atoms or functional groups, were obtained through the Diels-Alder synthesis and have shown in vitro antimicrobial and antioxidant properties [4].

Among the 2-(9H-fluoren-9-yl-methoxycarbonylamino)-propionic acid 3-(2-substituted-quinolin-3-yl)-isoxazol-5-yl-methyl esters, having the quinoline ring 2-substituted with various radicals, compounds with -SH and -SeH groups, exhibited good antibacterial activity against Gram-positive and Gram-negative bacteria (Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtillis), compared to the ciprofloxacin standard [5].

Fluorenones have various therapeutic applications. Thus, tilorone has antiviral properties, benfluron is antineoplastic, and fluodipine is a cardiodepressant agent. The 9-fluorenone class includes many potentially active substances, which can be studied to optimize lead molecules in several therapeutic areas ( ).

The study of the influence of tilorone (2,7-bis(2-diethylaminoethoxy)fluoren-9-one) on the activity of Staphylococcus aureus DnaG primase showed that it is inhibited by tilorone, although no inhibition of staphylococcal growth in the presence of this compound was observed. Structural modulations were performed to facilitate the diffusion of the compound into the bacterial cell, to inhibit bacterial growth and also to identify a promising lead compound. Thus, different derivatives of 9-fluorenone were synthesized, using tilorone as structural model, and adding hydrocarbon chains with different lengths and different terminal groups. These compounds were tested against Gram-positive and Gram-negative bacteria, and some exhibited a relatively low inhibitory concentration on Bacillus anthracis, methicillin-resistant Staphylococcus aureus, Burkholderia thailandensis, and Francisella tularensis. The results also demonstrated that the biodistribution of tilorone can be improved by further altering the chain length, the resulting compounds being used as prototype molecules to design and develop future stronger and more potent antimicrobial drugs [6].

If you are looking for more details, kindly visit pd(dppf)cl2.dcm.

In addition, 9-Fluorenon-4-carboxamides have been obtained as tilorone analogues and their cytotoxicity, antiviral, and cytokine-inducing properties have been demonstrated [7].

Using 9-fluorenone, Schiff bases were synthesized and investigated for their biological activity using molecular docking against a bacterial protein (Proteus mirabilis catalase). Among the tested molecules, N,N’-bis-Fluoren-9-yliden-ethane-1,2-diamine revealed the highest docking score (81,947). Some of the compounds exhibited antimicrobial activity against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae comparable to the standard antibiotic, streptomycin, at a concentration of 100 μg/mL [8].

A new series of 2,7-diamidofluorenones was synthesized, the study showing that some compounds have good antiproliferative activity, acting as type I topoisomerase inhibitors. It was found that the introduction of the linear alkyl group in the side chains resulted in better antiproliferative activity, comparing with compounds having a branched alkyl group or a bulky group. Compared to tertiary amino groups, the presence of secondary amino groups in the side chains is increasing the antiproliferative activity. The results indicated that the fluorenone fragment could be a potential pharmacophore for the design of antitumor compounds in the class of topoisomerase inhibitors IB [9].

Fluorenone derivatives have been also reported to possess potent antioxidant activity [10,11].

The choice of the carbamoyloximinic moiety in the structure of the compounds covered by this paper is also based on the fact that this moiety is found in the structure of other compounds with antibacterial and antifungal action, such as N-R-carbamoyl-2-adamantanoxime [12] or antimycobacterial, N,N-dimethylcarbamoyloxime 2-bromo-6-R-indeno[2,1-c]quinolin-7-one [13] or is also found in the structure of compounds known as acaricides, insecticides and/or nematocides (alanicarb, aldicarb, aldoxicarb, tirpate, oxamyl), as well as pesticides, such as N-methyl-N-[(tert-butylphenyl)sulfenyl] carbamoyloxime derivatives [14].

This structural feature of carbamate oxime, present in the molecule of some compounds, contributes to the improvement of their pharmacological and pharmacokinetic properties [15].

This article is focused on O-aryl-carbamoyl-oxymino-fluoren derivatives combining several pharmacophoric fragments, i.e., the fluorenic tricyclic system, carbamoyl and oximinic groups. The new derivatives were obtained by refluxing 9H-fluoren-9-one oxime with arylisocyanates and were characterized by their physical constants and spectroscopic data.

The nanotechnological approaches are more and more present in most fields of human activity and offer great expectations for the infection control too, by providing solutions for novel antimicrobial strategies, effective against both planktonic and adherent microbes, or by the improvement of current ones [16]. Among nanostructures, metal oxide nanomaterials (e.g., zinc oxide, copper oxide, magnetite) have gain particular attention, due to their intrinsic antimicrobial activity [17,18], but also to their ability to be used as nanoshuttles for the delivery of antimicrobial compounds. Starting from this evidence, our aim was to investigate the potential of magnetite@citrate core@shell nanostructures to improve the antimicrobial properties of newly synthesized fluorenones. These nanoparticles have many advantages for biomedical applications, such as increased biocompatibility and capacity to incorporate and release many therapeutic compounds, thus decreasing the required active concentration and the potential toxic effects [19,20,21,22]. These magnetic nanostructures should be exploited because the low dimensionality of these carriers can assure higher internalisation into the cells [23].

The antimicrobial activity was evaluated against bacterial and fungal strains, in planktonic and biofilms growth state, using quantitative assays, to determine the minimum inhibitory concentration (MIC) and the minimum biofilm eradication concentration (MBEC).

The company is the world’s best Precious Metal Catalysts supplier. We are your one-stop shop for all needs. Our staff are highly-specialized and will help you find the product you need.