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New Antibacterial Agents 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 6759

Special Issue Editor

Division of Medical Biology, Jan Kochanowski University, 25-406 Kielce, Poland
Interests: clinical biochemistry; anticancer drugs; cytotoxicity; gene expression; drugs diffusion; new antibacterial agents; host–pathogen interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The increase of antibiotic resistance in bacteria highlights the urgent need for improved antibacterial agents. There are interesting new agents with antibacterial potential but with modes of action that are not fully known, or well-known modified drugs with patterns of toxicity, effectiveness, and/or other related properties that need to be investigated. These new ways/agents are mainly targeted into bacterial virulence factors, cell division machinery, biofilm formation, or cell membrane disruption. It seems to be crucial to determine their antibacterial mechanisms and effectiveness in comparison to cytotoxicity against eukaryotic cells as a potential new agent for clinical application in the future.

Nanoparticles, naturally obtained antibacterials, synthetic or semi-synthetic agents which are chemically altered natural products, metal complexes, peptides, or bacteriophages and their lytic proteins are considered as new antibacterial agents.

In an attempt to bring together recent advances in this field, I will edit the new edition on the topic “New Antibacterial Agents” in the International Journal of Molecular Sciences (IF:5.924). This Special Issue is focused on the effectiveness, mode of action, and cytotoxic activity of new antibacterial agents. Since IJMS is a journal of molecular science, pure clinical studies will not suitable for the journal. However, clinical submissions with biomolecular experiments are welcomed.

Dr. Michał Arabski
Guest Editor

Manuscript Submission Information

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Keywords

  • antibacterial agents
  • antibiotic resistance
  • bacterial virulence factors
  • cell division machinery
  • biofilm formation
  • cell membrane disruption
  • natural products
  • metal complexes
  • peptides
  • bacteriophages
  • lytic proteins

Related Special Issue

Published Papers (4 papers)

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Research

14 pages, 1748 KiB  
Article
Dalbavancin Boosts the Ability of Neutrophils to Fight Methicillin-Resistant Staphylococcus aureus
Int. J. Mol. Sci. 2023, 24(3), 2541; https://doi.org/10.3390/ijms24032541 - 28 Jan 2023
Cited by 1 | Viewed by 1420
Abstract
Polymorphonuclear leukocytes (PMNs) are the most important cell type involved in the early nonspecific host response to bacterial pathogens. Staphylococcus aureus has evolved mechanisms to evade immune responses that contribute to its persistence in PMNs, and acquired resistance to several antimicrobials. Additionally, methicillin-resistant [...] Read more.
Polymorphonuclear leukocytes (PMNs) are the most important cell type involved in the early nonspecific host response to bacterial pathogens. Staphylococcus aureus has evolved mechanisms to evade immune responses that contribute to its persistence in PMNs, and acquired resistance to several antimicrobials. Additionally, methicillin-resistant S. aureus (MRSA) is one of the most common causes of acute bacterial skin and skin-structure infections (ABSSSIs). Dalbavancin (DBV), a lipoglycopeptide, is indicated for the treatment of ABSSSIs, and has a broad spectrum of action against most microorganisms. Here, we sought to determine the effect of DBV on the neutrophil killing of MRSA and its potential immunomodulating activity. Our results revealed that DBV boosts MRSA killing by acting on both bacteria and PMNs. DBV pre-treatment of PMNs did not change the respiratory burst or degranulation, while an increased trend in neutrophil extracellular traps-associated elastase and in the production of TNFα and CXCL8 was revealed. In parallel, DBV caused a delay in the apoptosis of MRSA-infected neutrophils. In conclusion, we demonstrated a cooperative effect between the antimicrobial properties of PMNs and DBV, thus owing to their immunomodulatory activity. In the choice of the treatment management of serious S. aureus infections, DBV should be considered as an outstanding option since it reinforces PMNs pathogen clearance capability by exerting its effect directly, not only on MRSA but also on neutrophils. Full article
(This article belongs to the Special Issue New Antibacterial Agents 2.0)
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19 pages, 3540 KiB  
Article
Synthesis, Structural Characterization and Biological Activity Evaluation of Novel Cu(II) Complexes with 3-(trifluoromethyl)phenylthiourea Derivatives
Int. J. Mol. Sci. 2022, 23(24), 15694; https://doi.org/10.3390/ijms232415694 - 10 Dec 2022
Viewed by 1482
Abstract
Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. [...] Read more.
Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells. Full article
(This article belongs to the Special Issue New Antibacterial Agents 2.0)
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22 pages, 4705 KiB  
Article
Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections
Int. J. Mol. Sci. 2022, 23(23), 15090; https://doi.org/10.3390/ijms232315090 - 01 Dec 2022
Cited by 1 | Viewed by 1278
Abstract
A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates [...] Read more.
A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15–5.57 µM) as well as anti-enterococcal (MICs/MBCs 2.34–44.5 µM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 µM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 µM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules. Full article
(This article belongs to the Special Issue New Antibacterial Agents 2.0)
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15 pages, 11610 KiB  
Article
Discovery of Epipodophyllotoxin-Derived B2 as Promising XooFtsZ Inhibitor for Controlling Bacterial Cell Division: Structure-Based Virtual Screening, Synthesis, and SAR Study
Int. J. Mol. Sci. 2022, 23(16), 9119; https://doi.org/10.3390/ijms23169119 - 14 Aug 2022
Cited by 6 | Viewed by 1676
Abstract
The emergence of phytopathogenic bacteria resistant to antibacterial agents has rendered previously manageable plant diseases intractable, highlighting the need for safe and environmentally responsible agrochemicals. Inhibition of bacterial cell division by targeting bacterial cell division protein FtsZ has been proposed as a promising [...] Read more.
The emergence of phytopathogenic bacteria resistant to antibacterial agents has rendered previously manageable plant diseases intractable, highlighting the need for safe and environmentally responsible agrochemicals. Inhibition of bacterial cell division by targeting bacterial cell division protein FtsZ has been proposed as a promising strategy for developing novel antibacterial agents. We previously identified 4′-demethylepipodophyllotoxin (DMEP), a naturally occurring substance isolated from the barberry species Dysosma versipellis, as a novel chemical scaffold for the development of inhibitors of FtsZ from the rice blight pathogen Xanthomonas oryzae pv. oryzae (Xoo). Therefore, constructing structure−activity relationship (SAR) studies of DMEP is indispensable for new agrochemical discovery. In this study, we performed a structure−activity relationship (SAR) study of DMEP derivatives as potential XooFtsZ inhibitors through introducing the structure-based virtual screening (SBVS) approach and various biochemical methods. Notably, prepared compound B2, a 4′-acyloxy DMEP analog, had a 50% inhibitory concentration of 159.4 µM for inhibition of recombinant XooFtsZ GTPase, which was lower than that of the parent DMEP (278.0 µM). Compound B2 potently inhibited Xoo growth in vitro (minimum inhibitory concentration 153 mg L−1) and had 54.9% and 48.4% curative and protective control efficiencies against rice blight in vivo. Moreover, compound B2 also showed low toxicity for non-target organisms, including rice plant and mammalian cell. Given these interesting results, we provide a novel strategy to discover and optimize promising bactericidal compounds for the management of plant bacterial diseases. Full article
(This article belongs to the Special Issue New Antibacterial Agents 2.0)
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