scholarly journals Novel Aminoguanidine Hydrazone Analogues: From Potential Antimicrobial Agents to Potent Cholinesterase Inhibitors

2021 ◽  
Vol 14 (12) ◽  
pp. 1229
Author(s):  
Martin Krátký ◽  
Šárka Štěpánková ◽  
Klára Konečná ◽  
Katarína Svrčková ◽  
Jana Maixnerová ◽  
...  
Keyword(s):  
Mixed Type ◽  
Cholinesterase Inhibitors ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Trichophyton Mentagrophytes ◽  
Substitution Pattern ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Ic50 Values ◽  
Further Development

A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50–99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. The compounds were effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) from 7.8 µM, as well as Gram-negative strains with higher MIC. Antifungal evaluation against yeasts and Trichophyton mentagrophytes found MIC from 62.5 µM. We also evaluated inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The compounds inhibited both enzymes with IC50 values of 17.95–54.93 µM for AChE and ≥1.69 µM for BuChE. Based on the substitution, it is possible to modify selectivity for a particular cholinesterase as we obtained selective inhibitors of either AChE or BuChE, as well as balanced inhibitors. The compounds act via mixed-type inhibition. Their interactions with enzymes were studied by molecular docking. Cytotoxicity was assessed in HepG2 cells. The hydrazones differ in their toxicity (IC50 from 5.27 to >500 µM). Some of the derivatives represent promising hits for further development. Based on the substitution pattern, it is possible to modulate bioactivity to the desired one.

scholarly journals Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

scholarly journals Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 989
Author(s):  
Martin Krátký ◽  
Katarína Svrčková ◽  
Quynh Anh Vu ◽  
Šárka Štěpánková ◽  
Jarmila Vinšová
Keyword(s):  
Biological Activity ◽  
Mixed Type ◽  
Cholinesterase Inhibitors ◽  
Eukaryotic Cell ◽  
Structure Activity ◽  
Aliphatic Ketones ◽  
Ic50 Values ◽  
Central Nervous Systems ◽  
Dual Inhibition ◽  
Potential Inhibitors

Based on the broad spectrum of biological activity of hydrazide–hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman’s spectrophotometric method. The hydrazide–hydrazones produced a dual inhibition of both cholinesterase enzymes with IC50 values of 46.8–137.7 µM and 19.1–881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N’-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure–activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF3-hydrazide–hydrazone scaffold.

scholarly journals Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 170
Author(s):  
Urszula Kosikowska ◽  
Monika Wujec ◽  
Nazar Trotsko ◽  
Wojciech Płonka ◽  
Piotr Paneth ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Resistant Bacteria ◽  
Binding Affinities ◽  
Substitution Pattern ◽  
Minimal Inhibitory Concentrations ◽  
Gram Positive Bacteria ◽  
Structure Activity ◽  
Drug Resistant Bacteria ◽  
Reference Strains

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

scholarly journals Construction of Leaderless-Bacteriocin-Producing Bacteriophage Targeting E. coli and Neighboring Gram-Positive Pathogens

2021 ◽  
Author(s):  
Yoshimitsu Masuda ◽  
Shun Kawabata ◽  
Tatsuya Uedoi ◽  
Ken-ichi Honjoh ◽  
Takahisa Miyamoto
Keyword(s):  
Antimicrobial Agents ◽  
Host Strain ◽  
Phage Resistance ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
T7 Phage

We demonstrated that we could combine LLB and phage to construct promising novel antimicrobial agents, LLB-phage. The first LLB-phage, lnqQ -T7 phage, can control the growth of both the Gram-negative host strain and neighboring Gram-positive bacteria while preventing the emergence of phage resistance in the host strain.

scholarly journals Synthesis of cyclotetrapeptide analogues of c-PLAI and evaluation of their antimicrobial properties

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Rani Maharani ◽  
Orin Inggriani Napitupulu ◽  
Jelang M. Dirgantara ◽  
Ace Tatang Hidayat ◽  
Dadan Sumiarsa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Properties ◽  
Trichophyton Mentagrophytes ◽  
Solution Phase ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Aromatic Residues ◽  
Gram Positive Bacteria ◽  
Lysine Residues ◽  
Bacteria And Fungi

Antimicrobial peptides (AMPs) are interesting compounds owing to their ability to kill several pathogens. In order to identify new AMPs, c-PLAI analogues were synthesized and evaluated together with their linear precursors for their antimicrobial properties against two Gram-positive bacteria ( Staphylococcus aureus and Bacillus cereus ), two Gram-negative bacteria ( Escherichia coli and Klebsiella pneumoniae ), and two fungal strains ( Candida albicans and Trichophyton mentagrophytes ). The new c-PLAI analogues were prepared through a combination of solid- and solution-phase syntheses, as previously employed for the synthesis of c-PLAI. The antimicrobial activity tests showed that the synthetic parent peptide c-PLAI was inactive or weakly active towards the bioindicators employed in the assay. The tests also indicated that cyclic c-PLAI analogues possessed enhanced antimicrobial properties against most of the bacteria and fungi tested. Furthermore, this study revealed that analogues containing cationic lysine residues displayed the highest activity towards most bioindicators. A combination of lysine and aromatic residues yielded analogues with broad-spectrum antimicrobial properties.

scholarly journals Chemical Composition and Antimicrobial Activity of Two Sri Lankan Lichens, Parmotrema rampoddense, and Parmotrema tinctorum against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Polwatta Samaraweera Arachchige Ishara Shiromi ◽  
Ruwani Punyakanthi Hewawasam ◽  
Rankoth Gedara Udeni Jayalal ◽  
Hasanga Rathnayake ◽  
Weerasinghe Mudiyanselage Dilip Gaya Bandara Wijayaratne ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Chemical Composition ◽  
Secondary Metabolites ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Ethanol Extract ◽  
Aqueous Extracts ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Parmotrema Tinctorum

Introduction. Medicinal utility of lichens is ascribed to the presence of various secondary metabolites of low molecular weight and they have been used in traditional medicine including Ayurveda in the treatment of wounds and skin disorders. Despite the urgent need to effectively address the antibiotic resistance worldwide, the discovery of new antibacterial drugs has declined in the recent past. This emphasizes the increasing importance of investigating and developing new classes of antibiotics that can withstand antibiotic resistance. Aims of the study. The present study was conducted to investigate the chemical composition and the antibacterial activity of hexane, ethanol, and aqueous extracts of Parmotrema rampoddense and Parmotrema tinctorum, two lichens collected from Belihuloya, Sri Lanka, against Gram-negative and Gram-positive bacteria including twenty clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Materials and methods. Phytochemical analysis, thin layer chromatography (TLC), and Gas Chromatography Mass Spectrometry (GC-MS) were performed to determine the chemical composition of the two lichens. Hexane, ethanol, and aqueous extracts of both lichens were tested against clinical isolate of Gram-negative and Gram-positive bacteria including twenty clinical isolates of MRSA. Bacterial susceptibility was tested using a disc diffusion assay. Minimum inhibitory concentration (MIC) was determined by a broth microdilution method. Vancomycin was used as the positive control. Results. Alectorialic acid, atranorin, atraric acid, orcinol, and O-orsellinaldehyde were among the secondary metabolites identified by the TLC and GC-MS analysis. None of the lichen extracts were active against Gram-negative bacteria but both lichens showed a concentration-dependent activity against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA. Ethanol extract of P. rampoddense showed the highest activity against MSSA with the MIC, 0.0192 mg/ml, but all MRSA isolates investigated showed MIC between 0.096 and 2.4 mg/ml for the same extract. Conclusion. Both lichens, P. rampoddense and P. tinctorum, represent potentially important sources of future antimicrobial drugs. Further investigation on the ethanol extract of P. rampoddense will enable us to determine the most active phytoconstituents responsible for the activity, their mechanism of action against bacterial pathogens, and also their cytotoxicity against normal cells.

scholarly journals Synthesis, Antibacterial and Antifungal Properties of Cyclohexane Tosyloxyimine Derivative

2019 ◽  
Vol 4 (3) ◽  
pp. 1-4
Author(s):  
Shoaib M
Keyword(s):  
Antimicrobial Agents ◽  
Sulfonyl Chloride ◽  
Antimicrobial Properties ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Bacteria And Fungi ◽  
Agar Well Diffusion Assay ◽  
Antibacterial And Antifungal ◽  
Candida Pseudotropicalis

Due to increasing antimicrobial resistance, functionally substituted cyclohexane derivatives are being explored as potential antimicrobial agents. Reaction of diethyl 4 - hydroxy - 6 - (hyd - roxyimino) - 4 - methyl - 2 - phenylcyclohexane - 1,3 - dicarboxylate with 4 - toluene sulfonyl chloride in boiling acetone in the presence of equimolar triethylamine resulted in formation of diethyl - 4 - hydroxy - 4 - methyl - 2 - phenyl - 6 - ((tosyloxy)imino) cyclohexane - 1,3 - dicarboxylate. The structure of novel compound was characterized by 1 H and 13 C NMR spectra and elemental analysis was performed. Agar well diffusion assay was used to screen novel compound against Gram - positive bacteria, Gram - negative bacteria and fungi. Test compound showed better antimicrobial properties against Gram - negative bac teria as compared to Gram - positive bacteria and fungi. Acinetobacter baumannii BDU - 32 was found to be most sensitive bacteria while Candida pseudotropicalis BDU MA88 was found to be most sensitive yeast.

scholarly journals Synthesis and Antimicrobial Evaluation of Side-Chain Derivatives based on Eurotiumide A

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 92
Author(s):  
Nakayama ◽  
Sato ◽  
Nakamura ◽  
Hamada ◽  
Nagano ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Iodine Atom ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Antimicrobial Activities ◽  
Side Chain ◽  
Negative Bacterium ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Antimicrobial Evaluation ◽  
Derivatives Of

Side-chain derivatives of eurotiumide A, a dihydroisochroman-type natural product, have been synthesized and their antimicrobial activities described. Sixteen derivatives were synthesized from a key intermediate of the total synthesis of eurotiumide A, and their antimicrobial activities against two Gram-positive bacteria, methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), and a Gram-negative bacterium, Porphyromonas gingivalis, were evaluated. The results showed that derivatives having an iodine atom on their aromatic ring instead of the prenyl moiety displayed better antimicrobial activity than eurotiumide A against MSSA and P. gingivalis. Moreover, we discovered that a derivative with an isopentyl side chain, which is a hydrogenated product of eurotiumide A, is the strongest antimicrobial agent against all three strains, including MRSA.

Redox-active cationic organoiron complex: a promising lead structure for developing antimicrobial agents with activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium

RSC Advances ◽  
2015 ◽  
Vol 5 (105) ◽  
pp. 86421-86427 ◽  
Author(s):  
Alaa S. Abd-El-Aziz ◽  
Christian Agatemor ◽  
Nola Etkin ◽  
David P. Overy ◽  
Russell G. Kerr
Keyword(s):  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Lead Structure ◽  
Gram Positive Bacteria ◽  
Redox Active ◽  
Vancomycin Resistant ◽  
Organoiron Complexes ◽  
Multidrug Resistant Strain

A redox-active, cationic organoiron complexes active against multidrug-resistant strain of Gram-positive bacteria is presented as a potential new lead structure for the design of antimicrobial agents.

scholarly journals Synthesis of Fluoroquinolones Derivatives as Antimicrobial Agents

2019 ◽  
Vol 35 (4) ◽  
pp. 1248-1253
Author(s):  
Lubna Swellmeen ◽  
Amal Uzrail ◽  
Rand Shahin ◽  
Yusuf AL-Hiari
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Carboxylic Acid ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Gram Negative Bacteria ◽  
Biological Test ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Derivatives Of

Fluoroquinolones are well known to have an anti-infective action. In the present study we described the synthesis of novel florouquinolones derivative as antimicrobial agent. The biological test highlighted a good inhibitory activity for the 7-Chloro-1-Alkyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derived synthons especially against pathogenic Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Streptococcus agalactiae). The binding interactions were monitored and could explain the good inhibitory activity of the synthesized derivatives of florouquinolones.

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