1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation

1,4-Naphthoquinones have antibacterial activity and are a promising new class of compound that can be used to treat bacterial infections. The goal was to improve effective antibacterial agents; therefore, we synthesized a new class of naphthoquinone hybrids, which contain phenylamino-phenylthio moieties as significant counterparts. Compound 4 was modified as a substituted aryl amide moiety, which enhanced the antibacterial activity of earlier compounds 3 and 4. In this study, five bacterial strains Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were used to evaluate the antibacterial potency of synthesized naphthoquinones using the minimal inhibitory concentration (MIC) method. Most of the studied naphthoquinones demonstrated major antibacterial activity with a MIC of 15.6 µg/mL–500 µg/mL. Selected compounds (5a, 5f and 5x) were studied for the mode of action, using intracellular ROS generation, determination of apoptosis by the Annexin V-FITC/PI assay, a bactericidal kinetic study and in silico molecular modelling. Additionally, the redox potentials of the specified compounds were confirmed by cyclic voltammetry (CV).

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Large-scale High-throughput Screening Revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as Novel Template for Antibacterial Agents

Current Drug Discovery Technologies ◽

10.2174/1570163816666190603095521 ◽

2020 ◽

Vol 17 (5) ◽

pp. 716-724

Author(s):

Yan A. Ivanenkov ◽

Renat S. Yamidanov ◽

Ilya A. Osterman ◽

Petr V. Sergiev ◽

Vladimir A. Aladinskiy ◽

...

Keyword(s):

Antibacterial Activity ◽

High Throughput ◽

High Throughput Screening ◽

Large Scale ◽

Antibacterial Agents ◽

Sos Response ◽

Luciferase Assay ◽

Translational Machinery ◽

E Coli ◽

New Class

Background: The key issue in the development of novel antimicrobials is a rapid expansion of new bacterial strains resistant to current antibiotics. Indeed, World Health Organization has reported that bacteria commonly causing infections in hospitals and in the community, e.g. E. Coli, K. pneumoniae and S. aureus, have high resistance vs the last generations of cephalosporins, carbapenems and fluoroquinolones. During the past decades, only few successful efforts to develop and launch new antibacterial medications have been performed. This study aims to identify new class of antibacterial agents using novel high-throughput screening technique. Methods: We have designed library containing 125K compounds not similar in structure (Tanimoto coeff.< 0.7) to that published previously as antibiotics. The HTS platform based on double reporter system pDualrep2 was used to distinguish between molecules able to block translational machinery or induce SOS-response in a model E. coli system. MICs for most active chemicals in LB and M9 medium were determined using broth microdilution assay. Results: In an attempt to discover novel classes of antibacterials, we performed HTS of a large-scale small molecule library using our unique screening platform. This approach permitted us to quickly and robustly evaluate a lot of compounds as well as to determine the mechanism of action in the case of compounds being either translational machinery inhibitors or DNA-damaging agents/replication blockers. HTS has resulted in several new structural classes of molecules exhibiting an attractive antibacterial activity. Herein, we report as promising antibacterials. Two most active compounds from this series showed MIC value of 1.2 (5) and 1.8 μg/mL (6) and good selectivity index. Compound 6 caused RFP induction and low SOS response. In vitro luciferase assay has revealed that it is able to slightly inhibit protein biosynthesis. Compound 5 was tested on several archival strains and exhibited slight activity against gram-negative bacteria and outstanding activity against S. aureus. The key structural requirements for antibacterial potency were also explored. We found, that the unsubstituted carboxylic group is crucial for antibacterial activity as well as the presence of bulky hydrophobic substituents at phenyl fragment. Conclusion: The obtained results provide a solid background for further characterization of the 5'- (carbonylamino)-2,3'-bithiophene-4'-carboxylate derivatives discussed herein as new class of antibacterials and their optimization campaign.

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Robust Antibacterial Activity of Tungsten Oxide (WO3-X) Nanodots

10.1101/494260 ◽

2018 ◽

Author(s):

Guangxin Duan ◽

Lu Chen ◽

Zhifeng Jing ◽

Phil De Luna ◽

Lin Wen ◽

...

Keyword(s):

Electron Microscopy ◽

Antibacterial Activity ◽

Tungsten Oxide ◽

Bacterial Infections ◽

Antibacterial Agents ◽

Inorganic Materials ◽

Cell Counting ◽

Resonance Spectroscopy ◽

Synthetic Approach ◽

E Coli

AbstractAntibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO3-X), synthesized by a simple one-pot synthetic approach, was found to exhibit efficient antibacterial capabilities. The analyses with colony-forming units (CFU) showed excellent antibacterial activity of WO3-X against both gram-negative E. coli (Escherichia coli) and gram-positive S. aureus (Staphylococcus aureus) strains. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed clear damage to the bacterial cell membranes, which was further confirmed by molecular dynamics simulations. Additionally, exposure to simulated sunlight was found to further increase germicidal activity of WO3-X nanodots – a 30-minute exposure to sunlight (combining 50 μg/mL WO3-X nanodots) showed a 70% decrease in E. coli viability compared to without exposure. Electron spin resonance spectroscopy (ESR) was used to elucidate the underlying mechanism of this photocatalytic activity through the generation of hydroxyl radical species. Cell counting kit-8 (CCK-8) and the live/dead assay were further employed to evaluate the cytotoxicity of WO3-X nanodots on eukaryotic cells, which demonstrated their general biocompatibility. In all, our results suggest WO3-X nanodots have considerable potential in antibacterial applications, while also being biocompatible at large.

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Synthesis and antibacterial activity of some Schiff bases derived from 4-aminobenzoic acid

Journal of the Serbian Chemical Society ◽

10.2298/jsc0510155p ◽

2005 ◽

Vol 70 (10) ◽

pp. 1155-1162 ◽

Cited By ~ 70

Author(s):

Jigna Parekh ◽

Pranav Inamdhar ◽

Rathish Nair ◽

Shipra Baluja ◽

Sumitra Chanda

Keyword(s):

Molecular Structure ◽

Antibacterial Activity ◽

Benzoic Acid ◽

Schiff Bases ◽

Bacterial Strain ◽

Antibacterial Agents ◽

Aminobenzoic Acid ◽

Bacterial Strains ◽

E Coli ◽

Amino Benzoic Acid

The following Schiff bases have been synthesized: (1) 4-(2-chlorobenzylidene)amino benzoic acid JP1, (2) 4 (furan-2-ylmethylene)amino benzoic acid JP2, (3) 4-[(3-phenylallylidene)amino]benzoic acid JP3, (4) 4 (2-hydroxybenzylidene)amino benzoic acid JP4, (5) 4 (4-hydroxy-3-methoxybenzylidene)amino benzoic acid JP5 and (6) 4 (3-nitrobenzylidene)amino benzoic acid JP6. They were screened as potential antibacterial agents against a number of medically important bacterial strains. The antibacterial activity was studied against A. faecalis ATCC 8750, E. aerogenes ATCC 13048, E. coli ATCC 25922, K. pneumoniae NCIM 2719 S. aureus ATCC 25923, P. vulgaris NCIM 8313, P. aeruginosa ATCC 27853 and S. typhimurium ATCC 23564. The antibacterial activity was evaluated using the Agar Ditch method. The solvents used were 1,4-dioxane and dimethyl sulfoxide. Different effects of the compounds were found in the bacterial strains in vestigated and the solvents used, suggesting, once again, that the antibacterial activity is dependent on the molecular structure of the compound, the solvent used and the bacterial strain under consideration. In the present work, 1,4-dioxane proved to be a good solvent in inhibiting the above stated bacterial strains.

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Synthesis, Characterization and Antimicrobial Activity of 4-Substituted-Benzylpiperazinyl Methanone Derivatives

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2017.10.2.7 ◽

2017 ◽

Vol 10 (2) ◽

pp. 3684-3687

Author(s):

Mahesh Chidara ◽

Satla Shobha Rani

Keyword(s):

Antibacterial Activity ◽

Antifungal Activity ◽

Bacterial Infections ◽

Antibacterial Agents ◽

Mass Spectral Data ◽

Future Studies ◽

Mass Spectral ◽

E Coli ◽

H Nmr ◽

Good Antibacterial Activity

Novel antibacterial compounds are needed to combat the emerging bacterial infections. In this study, synthesis of 4-substituted benzylpiperazin-1-yl methanone derivatives was carried out by 4-substituted benzyl chloride (I) with piperazine in presence of ethanol to obtain 4-substituted benzylpiperazines (II). Benzylpiperazines (II) was condensed with different substituted esters in presence of diluted acid to produce title compounds (IIIa–e, IVa-e and Va-e). All the title compounds were screened for possible antibacterial activity against P. Vulgaris, S. Aureas, E. Coli, B. Subtillus and antifungal activity against Altenaria, Culvalaria, C. Albicans and A. Niger. Among the compounds synthesized IVb, IVd and IVf demonstrated good antibacterial activity; IVb, IVc, and IVe showed good antifungal activity. The activities of the synthesized compounds are compared with the standard and other test compounds. The structures of synthesized compounds were established by elemental analysis, IR, H NMR and Mass spectral data. Future studies will confirm their efficacy and utility as antibacterial agents.

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Synthesis, Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido, Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives

Molecules ◽

10.3390/molecules26020357 ◽

2021 ◽

Vol 26 (2) ◽

pp. 357

Author(s):

Ebraheem Abdu Musad Saleh ◽

Abdullah Mohammed AL Dawsari ◽

Kakul Husain ◽

Ismail Hassan Kutty ◽

K.M.Lokanatha Rai

Keyword(s):

Antibacterial Activity ◽

Heterocyclic Compounds ◽

Antibacterial Agents ◽

Biological Evaluation ◽

Bacterial Strains ◽

E Coli ◽

Antioxidant Evaluation ◽

Synthetic Approaches ◽

Membered Heterocycle ◽

Molecular Framework

A novel synthesis of thiazolo[2,3-b]quinazolines 4(a–e), pyrido[2′,3′:4,5]thiazolo[2,3-b]quinazolines {5(a–e), 6(a–e), and 7(a–e)}, pyrano[2′,3′:4,5]thiazolo[2,3-b]quinazolines 8(a–e), and benzo[4,5]thiazolo[2,3-b]quinazoloine9(a–e) derivatives starting from 2-(Bis-methylsulfanyl-methylene)-5,5-dimethyl-cyclohexane-1,3-dione 2 as efficient α,α dioxoketen dithioacetal is reported and the synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antibacterial agents against the bacterial strains, like S. aureus, E. coli, and P. aeruginosa. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 μg/mL while the others exhibited better antibacterial activity at 100 μg/mL. The results of this study showed that compound 6(c) possessed remarkable antibacterial activity, whereas compound 9(c) exhibited the highest efficacy as an antioxidant. The structures of the new synthetic compounds were elucidated by elemental analysis, IR, 1H-NMR, and 13C-NMR.

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SOFT CORAL (Sinularia sp.) EXTRACTS WITH ANTIBACTERIAL ACTIVITY

Omni-Akuatika ◽

10.20884/1.oa.2018.14.1.375 ◽

2018 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Wendy Alexander Tanod ◽

Anita Treisya Aristawati ◽

Masteria Yunovilsa Putra ◽

Muliadin Muliadin

Keyword(s):

Antibacterial Activity ◽

Pathogenic Bacteria ◽

Antibacterial Agents ◽

Soft Coral ◽

Solvent Polarity ◽

Soft Corals ◽

Bacterial Strains ◽

E Coli ◽

High Antibacterial Activity ◽

And Staphylococcus Aureus

There is a growing need for new antibacterial agents, in particular because many antibiotics are becoming ineffective due to the emergence of resistant bacterial strains. Soft corals of the Genus Sinularia, Family Alcyoniidae, have potential as a source of terpenoid and steroid compounds with antibacterial activity. These corals may vary in external morphology (shape, colour, size).The aim of this research was to identify extracted fractions with high antibacterial activity. Sinularia sp. specimens were extracted, fractionated based on solvent polarity, and tested for antibacterial bioactivity against pathogenic bacteria (Escherichia coli and Staphylococcus aureus). Antibacterial activity of the three fractions varied in strength. The dichloromethane fraction showed strong antibacterial activity, inhibiting S. aureus and E. coli growth at a concentration of 1 mg ml-1, while the ethyl acetate and ethanol fractions were effective at 10 mg ml-1 and 100 mg ml-1, respectively.

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Recent Advances in 1,3,5-Triazine Derivatives as Antibacterial Agents

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x17666200129094032 ◽

2020 ◽

Vol 17 (8) ◽

pp. 991-1041

Author(s):

Divya Utreja ◽

Jagdish Kaur ◽

Komalpreet Kaur ◽

Palak Jain

Keyword(s):

Antibacterial Activity ◽

Heterocyclic Compounds ◽

Antibacterial Agents ◽

Rapid Development ◽

Pharmacological Action ◽

Biological Properties ◽

Vast Array ◽

Bacterial Diseases ◽

New Class ◽

Triazine Derivatives

Triazine, one of the nitrogen containing heterocyclic compounds has attracted the considerable interest of researchers due to the vast array of biological properties such as anti-viral, antitumor, anti-convulsant, analgesic, antioxidant, anti-depressant, herbicidal, insecticidal, fungicidal, antibacterial and anti-inflammatory activities offered by it. Various antibacterial agents have been synthesized by researchers to curb bacterial diseases but due to rapid development in drug resistance, tolerance and side effects, there had always been a need for the synthesis of a new class of antibacterial agents that would exhibit improved pharmacological action. Therefore, this review mainly focuses on the various methods for the synthesis of triazine derivatives and their antibacterial activity.

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Fluoroquinolone-3-carboxamide Amino Acid Conjugates: Synthesis, Antibacterial Properties And Molecular Modeling Studies

Medicinal Chemistry ◽

10.2174/1573406415666190904143852 ◽

2020 ◽

Vol 17 (1) ◽

pp. 71-84

Author(s):

Riham M. Bokhtia ◽

Siva S. Panda ◽

Adel S. Girgis ◽

Hitesh H. Honkanadavar ◽

Tarek S. Ibrahim ◽

...

Keyword(s):

Experimental Data ◽

Antibacterial Activity ◽

Amino Acid ◽

Bacterial Infections ◽

Antibacterial Agents ◽

Antibacterial Properties ◽

Computational Studies ◽

Protecting Group ◽

Amino Acid Conjugates ◽

Molecular Modeling Studies

Background: Bacterial infections are considered as one of the major global health threats, so it is very essential to design and develop new antibacterial agents to overcome the drawbacks of existing antibacterial agents. Method: The aim of this work is to synthesize a series of new fluoroquinolone-3-carboxamide amino acid conjugates by molecular hybridization. We utilized benzotriazole chemistry to synthesize the desired hybrid conjugates. Result: All the conjugates were synthesized in good yields, characterized, evaluated for their antibacterial activity. The compounds were screened for their antibacterial activity using methods adapted from the Clinical and Laboratory Standards Institute. Synthesized conjugates were tested for activity against medically relevant pathogens; Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27856) Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 19433). Conclusion: The observed antibacterial experimental data indicates the selectivity of our synthesized conjugates against E.Coli. The protecting group on amino acids decreases the antibacterial activity. The synthesized conjugates are non-toxic to the normal cell lines. The experimental data were supported by computational studies.

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Beehive Products as Antibacterial Agents: A Review

Antibiotics ◽

10.3390/antibiotics10060717 ◽

2021 ◽

Vol 10 (6) ◽

pp. 717

Author(s):

Rita Abou Nader ◽

Rawan Mackieh ◽

Rim Wehbe ◽

Dany El El Obeid ◽

Jean Marc Sabatier ◽

...

Keyword(s):

Antibacterial Activity ◽

Honey Bee ◽

Antibacterial Agents ◽

Royal Jelly ◽

Biological Activities ◽

Vital Role ◽

Bee Venom ◽

Bacterial Strains ◽

Wide Range ◽

Life Threatening

Honeybees are one of the most marvelous and economically beneficial insects. As pollinators, they play a vital role in every aspect of the ecosystem. Beehive products have been used for thousands of years in many cultures for the treatment of various diseases. Their healing properties have been documented in many religious texts like the Noble Quran and the Holy Bible. Honey, bee venom, propolis, pollen and royal jelly all demonstrated a richness in their bioactive compounds which make them effective against a variety of bacterial strains. Furthermore, many studies showed that honey and bee venom work as powerful antibacterial agents against a wide range of bacteria including life-threatening bacteria. Several reports documented the biological activities of honeybee products but none of them emphasized on the antibacterial activity of all beehive products. Therefore, this review aims to highlight the antibacterial activity of honey, bee venom, propolis, pollen and royal jelly, that are produced by honeybees.

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Alkaloid-Rich Crude Extracts, Fractions and Piperamide Alkaloids of Piper guineense Possess Promising Antibacterial Effects

Antibiotics ◽

10.3390/antibiotics7040098 ◽

2018 ◽

Vol 7 (4) ◽

pp. 98 ◽

Cited By ~ 5

Author(s):

Eunice Mgbeahuruike ◽

Pia Fyhrquist ◽

Heikki Vuorela ◽

Riitta Julkunen-Tiitto ◽

Yvonne Holm

Keyword(s):

Antibacterial Activity ◽

Pathogenic Bacteria ◽

Bacterial Resistance ◽

Hot Water ◽

Bacterial Strains ◽

Inhibitory Effects ◽

Piper Guineense ◽

E Coli ◽

Growth Inhibitory ◽

Derivatives Of

Piper guineense is a food and medicinal plant commonly used to treat infectious diseases in West-African traditional medicine. In a bid to identify new antibacterial compounds due to bacterial resistance to antibiotics, twelve extracts of P. guineense fruits and leaves, obtained by sequential extraction, as well as the piperine and piperlongumine commercial compounds were evaluated for antibacterial activity against human pathogenic bacteria. HPLC-DAD and UHPLC/Q-TOF MS analysis were conducted to characterize and identify the compounds present in the extracts with promising antibacterial activity. The extracts, with the exception of the hot water decoctions and macerations, contained piperamide alkaloids as their main constituents. Piperine, dihydropiperine, piperylin, dihydropiperylin or piperlonguminine, dihydropiperlonguminine, wisanine, dihydrowisanine and derivatives of piperine and piperidine were identified in a hexane extract of the leaf. In addition, some new piperamide alkaloids were identified, such as a piperine and a piperidine alkaloid derivative and two unknown piperamide alkaloids. To the best of our knowledge, there are no piperamides reported in the literature with similar UVλ absorption maxima and masses. A piperamide alkaloid-rich hexane leaf extract recorded the lowest MIC of 19 µg/mL against Sarcina sp. and gave promising growth inhibitory effects against S. aureus and E. aerogenes as well, inhibiting the growth of both bacteria with a MIC of 78 µg/mL. Moreover, this is the first report of the antibacterial activity of P. guineense extracts against Sarcina sp. and E. aerogenes. Marked growth inhibition was also obtained for chloroform extracts of the leaves and fruits against P. aeruginosa with a MIC value of 78 µg/mL. Piperine and piperlongumine were active against E. aerogenes, S. aureus, E. coli, S. enterica, P. mirabilis and B. cereus with MIC values ranging from 39–1250 µg/mL. Notably, the water extracts, which were almost devoid of piperamide alkaloids, were not active against the bacterial strains. Our results demonstrate that P. guineense contains antibacterial alkaloids that could be relevant for the discovery of new natural antibiotics.

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