Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
Small Molecules as Antimicrobials
share announcement

Small Molecules as Antimicrobials

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 61093

Special Issue Editor

Dr. Poce Giovanna

E-Mail Website
Guest Editor
Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Universitaà di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy
Interests: medicinal chemistry; drug development; antimycobacterials; antibacterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The World Health Organization (WHO) announced antimicrobial resistance (AMR) as a major threat to public health. The rapid development and spread of new resistance mechanisms has made many antimicrobials useless in treating clinically ill patients. Even medical procedures such as major surgery, organ transplantation, and cancer chemotherapy have become very risky in the absence of effective antimicrobials for prevention and treatment of infections. Therefore, there is an urgent need for new, better, and more effective antimicrobials.

We invite authors to submit original research and review articles related to up-to-date and ongoing research focusing on the development and evaluation of potential new antimicrobial agents, as well as on the investigation of improved delivery protocols of both existing and new antimicrobial agents. We aim to highlight research covering all stages of investigation, such as in silico studies, synthesis efforts, in vitro studies, and in vivo evaluations.

Potential topics include, but are not limited to:

  • Development and testing of novel and effective antimicrobial agents;
  • Antimicrobial agents active against drug-resistant forms;
  • Recent advances in antimicrobial drug delivery.

Prof. Poce Giovanna
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • medicinal chemistry
  • antimycobacterials
  • antibacterials

Related Special Issues

Published Papers (16 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

19 pages, 1360 KiB  
Article
The Nitrobenzoxadiazole Derivative NBDHEX Behaves as Plasmodium falciparum Gametocyte Selective Inhibitor with Malaria Parasite Transmission Blocking Activity
by Giulia Siciliano, Veronica Di Paolo, Dante Rotili, Rossella Migale, Francesca Pedini, Marialuisa Casella, Serena Camerini, Daniele Dalzoppo, Rob Henderson, Tonnie Huijs, Koen J. Dechering, Antonello Mai, Anna Maria Caccuri, Marco Lalle, Luigi Quintieri and Pietro Alano
Pharmaceuticals 2022, 15(2), 168; https://doi.org/10.3390/ph15020168 - 29 Jan 2022
Cited by 3 | Viewed by 3029
Abstract
This work describes the activity of 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX) and of its newly identified carboxylic acid metabolite on the human malaria parasite Plasmodium falciparum. NBDHEX has been previously identified as a potent cytotoxic agent against murine and human cancer cells as [...] Read more.
This work describes the activity of 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX) and of its newly identified carboxylic acid metabolite on the human malaria parasite Plasmodium falciparum. NBDHEX has been previously identified as a potent cytotoxic agent against murine and human cancer cells as well as towards the protozoan parasite Giardia duodenalis. We show here that NBDHEX is active in vitro against all blood stages of P. falciparum, with the rare feature of killing the parasite stages transmissible to mosquitoes, the gametocytes, with a 4-fold higher potency than that on the pathogenic asexual stages. This activity importantly translates into blocking parasite transmission through the Anopheles vector in mosquito experimental infections. A mass spectrometry analysis identified covalent NBDHEX modifications in specific cysteine residues of five gametocyte proteins, possibly associated with its antiparasitic effect. The carboxylic acid metabolite of NBDHEX retains the gametocyte preferential inhibitory activity of the parent compound, making this novel P. falciparum transmission-blocking chemotype at least as a new tool to uncover biological processes targetable by gametocyte selective drugs. Both NBDHEX and its carboxylic acid metabolite show very limited in vitro cytotoxicity on VERO cells. This result and previous evidence that NBDHEX shows an excellent in vivo safety profile in mice and is orally active against human cancer xenografts make these molecules potential starting points to develop new P. falciparum transmission-blocking agents, enriching the repertoire of drugs needed to eliminate malaria. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

13 pages, 436 KiB  
Article
Evaluation of New Antimicrobial Agents Based on tris(1H-Indol-3-yl)methylium Salts: Activity, Toxicity, Suppression of Experimental Sepsis in Mice
by Alexey S. Trenin, Elena B. Isakova, Michael I. Treshchalin, Vasilisa A. Polozkova, Elena P. Mirchink, Alexey A. Panov, Alexander Y. Simonov, Olga P. Bychkova, Victor V. Tatarskiy and Sergey N. Lavrenov
Pharmaceuticals 2022, 15(2), 118; https://doi.org/10.3390/ph15020118 - 19 Jan 2022
Cited by 2 | Viewed by 2129
Abstract
The antimicrobial activity and toxicity of three novel synthetic antibacterial agents containing tris(1H-indol-3-yl)methylium fragment were studied in vitro and in vivo. All compounds in vitro revealed high activity (minimal inhibitory concentration (MIC) 0.13–1.0 µg/mL) against bacteria that were either sensitive [...] Read more.
The antimicrobial activity and toxicity of three novel synthetic antibacterial agents containing tris(1H-indol-3-yl)methylium fragment were studied in vitro and in vivo. All compounds in vitro revealed high activity (minimal inhibitory concentration (MIC) 0.13–1.0 µg/mL) against bacteria that were either sensitive or resistant to antibiotics, including multidrug-resistant clinical isolates. The derivatives combining high antimicrobial activity with relatively low cytotoxicity against human donor fibroblasts HPF-hTERT were subjected to further testing on mice. In vivo they revealed fairly good tolerance and relatively low toxicity. Acute toxicity was evaluated, and the main indicators of toxicity, including LD50 and LD10, were determined. A study of compounds in vivo showed their efficiency in the model of staphylococcal sepsis in mice. The efficiency of compounds may be due to the ability of indolylmethylium salts to form pores in the cytoplasmic membrane of microbial cells and thereby facilitate the penetration of molecules into the pathogen. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

14 pages, 1069 KiB  
Article
Synthesis and Evaluation of 3-Halobenzo[b]thiophenes as Potential Antibacterial and Antifungal Agents
by Prerna J. Masih, Tanay Kesharwani, Elivet Rodriguez, Mia A. Vertudez, Mina L. Motakhaveri, Terelan K. Le, Minh Kieu T. Tran, Matthew R. Cloyd, Cory T. Kornman and Aimee M. Phillips
Pharmaceuticals 2022, 15(1), 39; https://doi.org/10.3390/ph15010039 - 28 Dec 2021
Cited by 3 | Viewed by 2303
Abstract
The global health concern of antimicrobial resistance has harnessed research interest to find new classes of antibiotics to combat disease-causing pathogens. In our studies, 3-halobenzo[b]thiophene derivatives were synthesized and tested for their antimicrobial activities using the broth microdilution susceptibility method. The [...] Read more.
The global health concern of antimicrobial resistance has harnessed research interest to find new classes of antibiotics to combat disease-causing pathogens. In our studies, 3-halobenzo[b]thiophene derivatives were synthesized and tested for their antimicrobial activities using the broth microdilution susceptibility method. The 3-halo substituted benzo[b]thiophenes were synthesized starting from 2-alkynyl thioanisoles using a convenient electrophilic cyclization methodology that utilizes sodium halides as the source of electrophilic halogens when reacted along with copper(II) sulfate. This environmentally benign methodology is facile, uses ethanol as the solvent, and results in 3-halo substituted benzo[b]thiophene structures in very high yields. The cyclohexanol-substituted 3-chloro and 3-bromobenzo[b]thiophenes resulted in a low MIC of 16 µg/mL against Gram-positive bacteria and yeast. Additionally, in silico absorption, distribution, metabolism, and excretion (ADME) properties of the compounds were determined. The compounds with the lowest MIC values showed excellent drug-like properties with no violations to Lipinski, Veber, and Muegge filters. The time-kill curve was obtained for cyclohexanol-substituted 3-chlorobenzo[b]thiophenes against Staphylococcus aureus, which showed fast bactericidal activity at MIC. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

15 pages, 2334 KiB  
Article
The Antibacterial Synthetic Flavonoid BrCl-Flav Exhibits Important Anti-Candida Activity by Damaging Cell Membrane Integrity
by Cornelia Babii, Mihaela Savu, Iuliana Motrescu, Lucian Mihail Birsa, Laura Gabriela Sarbu and Marius Stefan
Pharmaceuticals 2021, 14(11), 1130; https://doi.org/10.3390/ph14111130 - 06 Nov 2021
Cited by 6 | Viewed by 2613
Abstract
Infections caused by Candida are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with Candida infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. [...] Read more.
Infections caused by Candida are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with Candida infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. The aim of this study was to explore the antifungal potential of BrCl-flav-a representative of a new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against four Candida clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration along with the time kill assay indicated a strong antifungal effect of BrCl-flav against C. albicans, C. parapsilosis, C. krusei and C. glabrata. The investigation of anti-Candida mechanism of action using fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages leading to cell lysis. BrCl-flav also showed important anti-virulence properties against Candida spp., inhibiting biofilm formation and yeast to hyphal transition. A strong synergistic antifungal effect against C. albicans strain was observed when BrCl-flav was used in combination with fluconazole. BrCl-flav has a good potential to develop new effective antifungal agents in the context of Candida spp. multidrug resistance phenomenon. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

20 pages, 8895 KiB  
Article
Design, Synthesis, Biological Evaluation and In Silico Studies of Pyrazole-Based NH2-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors
by Jiqing Ye, Lin Lin, Jinyi Xu, Paul Kay-sheung Chan, Xiao Yang and Cong Ma
Pharmaceuticals 2021, 14(4), 371; https://doi.org/10.3390/ph14040371 - 16 Apr 2021
Cited by 6 | Viewed by 2562
Abstract
Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of [...] Read more.
Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH2-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

21 pages, 4682 KiB  
Article
Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents
by Vasilichia Antoci, Liliana Oniciuc, Dorina Amariucai-Mantu, Costel Moldoveanu, Violeta Mangalagiu, Andreea Madalina Amarandei, Claudiu N. Lungu, Simona Dunca, Ionel I. Mangalagiu and Gheorghita Zbancioc
Pharmaceuticals 2021, 14(4), 335; https://doi.org/10.3390/ph14040335 - 06 Apr 2021
Cited by 23 | Viewed by 3182
Abstract
We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps [...] Read more.
We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, 1H-NMR, 13C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

16 pages, 3058 KiB  
Article
Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity against HSV-1
by Kseniya A. Zhdanova, Inga O. Savelyeva, Artem V. Ezhov, Andrey P. Zhdanov, Konstantin Yu. Zhizhin, Andrey F. Mironov, Natal’ya A. Bragina, Alla A. Babayants, Irina S. Frolova, Nadezhda I. Filippova, Nadezhda N. Scliankina and Olga N. Scheglovitova
Pharmaceuticals 2021, 14(3), 242; https://doi.org/10.3390/ph14030242 - 08 Mar 2021
Cited by 8 | Viewed by 2191
Abstract
This work is devoted to the search for new antiherpes simplex virus type 1 (HSV-1) drugs among synthetic tetrapyrroles and to an investigation of their antiviral properties under nonphotodynamic conditions. In this study, novel amphiphilic 5,10,15,20-tetrakis(4-(3-pyridyl-n-propanoyl)oxyphenyl)porphyrin tetrabromide (3a), 5,10,15,20-tetrakis(4-(6-pyridyl- [...] Read more.
This work is devoted to the search for new antiherpes simplex virus type 1 (HSV-1) drugs among synthetic tetrapyrroles and to an investigation of their antiviral properties under nonphotodynamic conditions. In this study, novel amphiphilic 5,10,15,20-tetrakis(4-(3-pyridyl-n-propanoyl)oxyphenyl)porphyrin tetrabromide (3a), 5,10,15,20-tetrakis(4-(6-pyridyl-n-hexanoyl)oxyphenyl)porphyrin tetrabromide (3b) and known 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetraiodide (TMePyP) were synthesized, and their dark antiviral activity in vitro against HSV-1 was studied. The influence of porphyrin’s nanosized delivery vehicles based on Pluronic F127 on anti-HSV-1 activity was estimated. All the received compounds 3a, 3b and TMePyP showed virucidal efficiency and had an effect on viral replication stages. The new compound 3b showed the highest antiviral activity, close to 100%, with the lowest concentration, while the maximum TMePyP activity was observed with a high concentration; porphyrin 3a was the least active. The inclusion of the synthesized compounds in Pluronic F-127 polymeric micelles had a noticeable effect on antiviral activity only at higher porphyrin concentrations. Action of the received compounds differs by influence on the early or later reproduction stages. While 3a and TMePyP acted on all stages of the viral replication cycle, porphyrin 3b inhibited viral replication during the early stages of infection. The resulting compounds are promising for the development of utilitarian antiviral agents and, possibly, medical antiviral drugs. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

15 pages, 4425 KiB  
Article
Discovery of Substituted (2-Aminooxazol-4-yl)Isoxazole-3-carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants
by Joana Magalhães, Nina Franko, Samanta Raboni, Giannamaria Annunziato, Päivi Tammela, Agostino Bruno, Stefano Bettati, Stefano Armao, Costanza Spadini, Clotilde Silvia Cabassi, Andrea Mozzarelli, Marco Pieroni, Barbara Campanini and Gabriele Costantino
Pharmaceuticals 2021, 14(2), 174; https://doi.org/10.3390/ph14020174 - 23 Feb 2021
Cited by 6 | Viewed by 2559
Abstract
Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. [...] Read more.
Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of Salmonella thyphimurium serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound 5, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound 5 Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

14 pages, 2020 KiB  
Article
Can Leaves and Stems of Rubus idaeus L. Handle Candida albicans Biofilms?
by Clément Bernard, Camille Juin, Marine Vitry, Van Thanh Danh Le, Julien Verdon, Anne-Solène Toullec, Christine Imbert and Marion Girardot
Pharmaceuticals 2020, 13(12), 477; https://doi.org/10.3390/ph13120477 - 18 Dec 2020
Cited by 5 | Viewed by 2075
Abstract
Candida albicans is an opportunistic pathogen involved in many infections, especially linked to implanted medical devices. Its ability to form biofilms complicates the treatment of these infections as few molecules are active against sessile C. albicans. The aim of this study was [...] Read more.
Candida albicans is an opportunistic pathogen involved in many infections, especially linked to implanted medical devices. Its ability to form biofilms complicates the treatment of these infections as few molecules are active against sessile C. albicans. The aim of this study was to evaluate the potential of leaves, three-month-old and one-year-old stems of Rubus idaeus L. against C. albicans biofilm growth. Extractions with a polarity gradient were carried out on hydroacetonic extracts and followed by fractionation steps. The obtained extracts and fractions were tested for their anti-biofilm growth activity against C. albicans using XTT method. Compounds of active subfractions were identified by LC-MS. The hexane extracts from leaves and stems were the most active against the fungus with IC50 at 500 and 250 µg/mL. Their bioguided fractionation led to 4 subfractions with IC50 between 62.5 and 125 µg/mL. Most of the components identified in active subfractions were fatty acids and terpenoïds. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

21 pages, 964 KiB  
Article
Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of H. pylori Strains and AGS Cell Proliferation
by Francesca Sisto, Simone Carradori, Paolo Guglielmi, Carmen Beatrice Traversi, Mattia Spano, Anatoly P. Sobolev, Daniela Secci, Maria Carmela Di Marcantonio, Entela Haloci, Rossella Grande and Gabriella Mincione
Pharmaceuticals 2020, 13(11), 405; https://doi.org/10.3390/ph13110405 - 19 Nov 2020
Cited by 20 | Viewed by 5338
Abstract
This study reports on the synthesis, structural assessment, microbiological screening against several strains of H. pylori and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis, 1H/13C/19 [...] Read more.
This study reports on the synthesis, structural assessment, microbiological screening against several strains of H. pylori and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis, 1H/13C/19F NMR spectra and crystallographic studies. The structure-activity relationships evidenced that among ether derivatives the substitution with specific electron-withdrawing groups (CF3 and NO2) especially in the para position of the benzyl ring led to an improvement of the antimicrobial activity, whereas electron-donating groups on the benzyl ring and ethereal alkyl chains were not tolerated with respect to the parent compound (MIC/MBC = 64/64 µg/mL). Ester derivatives (coumarin-carvacrol hybrids) displayed a slight enhancement of the inhibitory activity up to MIC values of 8–16 µg/mL. The most interesting compounds exhibiting the lowest MIC/MBC activity against H. pylori (among others, compounds 16 and 39 endowed with MIC/MBC values ranging between 2/2 to 32/32 µg/mL against all the evaluated strains) were also assayed for their ability to reduce AGS cell growth with respect to 5-Fluorouracil. Some derivatives can be regarded as new lead compounds able to reduce H. pylori growth and to counteract the proliferation of AGS cells, both contributing to the occurrence of gastric cancer. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

16 pages, 1310 KiB  
Article
Design, Synthesis, and Antibacterial and Antifungal Activities of Novel Trifluoromethyl and Trifluoromethoxy Substituted Chalcone Derivatives
by Surendra Babu Lagu, Rajendra Prasad Yejella, Richie R. Bhandare and Afzal B. Shaik
Pharmaceuticals 2020, 13(11), 375; https://doi.org/10.3390/ph13110375 - 09 Nov 2020
Cited by 30 | Viewed by 4239
Abstract
Despite the availability of many drugs to treat infectious diseases, the problems like narrow antimicrobial spectrum, drug resistance, hypersensitivities and systemic toxicities are hampering their clinical utility. Based on the above facts, in the present study, we designed, synthesized and evaluated the antibacterial [...] Read more.
Despite the availability of many drugs to treat infectious diseases, the problems like narrow antimicrobial spectrum, drug resistance, hypersensitivities and systemic toxicities are hampering their clinical utility. Based on the above facts, in the present study, we designed, synthesized and evaluated the antibacterial and antifungal activity of novel fluorinated compounds comprising of chalcones bearing trifluoromethyl (A1–A10) and trifluoromethoxy (B1–B10) substituents. The compounds were characterized by spectroscopic techniques and evaluated for their antimicrobial activity against four pathogenic Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Bacillus subtilis) bacterial and fungal (Candida albicans and Aspergillus niger) strains. In this study, the compounds with trifluoromethoxy group were more effective than those with trifluoromethyl group. Among the 20 fluorinated chalcones, compound A3/B3 bearing an indole ring attached to the olefinic carbon have been proved to possess the most antimicrobial activity compared to the standard drugs without showing cytotoxicity on human normal liver cell line (L02). Further, the minimum inhibitory concentration (MIC) for A3/B3 was determined by serial tube dilution method and showed potential activity. These results would provide promising access to future study about the development of novel agents against bacterial and fungal infections. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

35 pages, 4104 KiB  
Review
Quorum Sensing Inhibitors to Quench P. aeruginosa Pathogenicity
by Marine Duplantier, Elodie Lohou and Pascal Sonnet
Pharmaceuticals 2021, 14(12), 1262; https://doi.org/10.3390/ph14121262 - 05 Dec 2021
Cited by 32 | Viewed by 4688
Abstract
The emergence and the dissemination of multidrug-resistant bacteria constitute a major public health issue. Among incriminated Gram-negative bacteria, Pseudomonas aeruginosa has been designated by the WHO as a critical priority threat. During the infection process, this pathogen secretes various virulence factors in order [...] Read more.
The emergence and the dissemination of multidrug-resistant bacteria constitute a major public health issue. Among incriminated Gram-negative bacteria, Pseudomonas aeruginosa has been designated by the WHO as a critical priority threat. During the infection process, this pathogen secretes various virulence factors in order to adhere and colonize host tissues. Furthermore, P. aeruginosa has the capacity to establish biofilms that reinforce its virulence and intrinsic drug resistance. The regulation of biofilm and virulence factor production of this micro-organism is controlled by a specific bacterial communication system named Quorum Sensing (QS). The development of anti-virulence agents targeting QS that could attenuate P. aeruginosa pathogenicity without affecting its growth seems to be a promising new therapeutic strategy. This could prevent the selective pressure put on bacteria by the conventional antibiotics that cause their death and promote resistant strain survival. This review describes the QS-controlled pathogenicity of P. aeruginosa and its different specific QS molecular pathways, as well as the recent advances in the development of innovative QS-quenching anti-virulence agents to fight anti-bioresistance. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

23 pages, 2632 KiB  
Review
Targeting Bacterial Sortases in Search of Anti-virulence Therapies with Low Risk of Resistance Development
by Georgiana Nitulescu, Denisa Margina, Anca Zanfirescu, Octavian Tudorel Olaru and George Mihai Nitulescu
Pharmaceuticals 2021, 14(5), 415; https://doi.org/10.3390/ph14050415 - 30 Apr 2021
Cited by 26 | Viewed by 3205
Abstract
Increasingly ineffective antibiotics and rapid spread of multi- and pan-resistant bacteria represent a global health threat; hence, the need of developing new antimicrobial medicines. A first step in this direction is identifying new molecular targets, such as virulence factors. Sortase A represents a [...] Read more.
Increasingly ineffective antibiotics and rapid spread of multi- and pan-resistant bacteria represent a global health threat; hence, the need of developing new antimicrobial medicines. A first step in this direction is identifying new molecular targets, such as virulence factors. Sortase A represents a virulence factor essential for the pathogenesis of Gram-positive pathogens, some of which have a high risk for human health. We present here an exhaustive collection of sortases inhibitors grouped by relevant chemical features: vinyl sulfones, 3-aryl acrylic acids and derivatives, flavonoids, naphtoquinones, anthraquinones, indoles, pyrrolomycins, isoquinoline derivatives, aryl β-aminoethyl ketones, pyrazolethiones, pyridazinones, benzisothiazolinones, 2-phenyl-benzoxazole and 2-phenyl-benzofuran derivatives, thiadiazoles, triazolothiadiazoles, 2-(2-phenylhydrazinylidene)alkanoic acids, and 1,2,4-thiadiazolidine-3,5-dione. This review focuses on highlighting their structure–activity relationships, using the half maximal inhibitory concentration (IC50), when available, as an indicator of each compound effect on a specific sortase. The information herein is useful for acquiring knowledge on diverse natural and synthetic sortases inhibitors scaffolds and for understanding the way their structural variations impact IC50. It will hopefully be the inspiration for designing novel effective and safe sortase inhibitors in order to create new anti-infective compounds and to help overcoming the current worldwide antibiotic shortage. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

28 pages, 4082 KiB  
Review
1,2,4-Triazoles as Important Antibacterial Agents
by Małgorzata Strzelecka and Piotr Świątek
Pharmaceuticals 2021, 14(3), 224; https://doi.org/10.3390/ph14030224 - 07 Mar 2021
Cited by 98 | Viewed by 9363
Abstract
The global spread of drug resistance in bacteria requires new potent and safe antimicrobial agents. Compounds containing the 1,2,4-triazole ring in their structure are characterised by multidirectional biological activity. A large volume of research on triazole and their derivatives has been carried out, [...] Read more.
The global spread of drug resistance in bacteria requires new potent and safe antimicrobial agents. Compounds containing the 1,2,4-triazole ring in their structure are characterised by multidirectional biological activity. A large volume of research on triazole and their derivatives has been carried out, proving significant antibacterial activity of this heterocyclic core. This review is useful for further investigations on this scaffold to harness its optimum antibacterial potential. Moreover, rational design and development of the novel antibacterial agents incorporating 1,2,4-triazole can help in dealing with the escalating problems of microbial resistance. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

33 pages, 6133 KiB  
Review
SAR Analysis of Small Molecules Interfering with Energy-Metabolism in Mycobacterium tuberculosis
by Federico Appetecchia, Sara Consalvi, Cristina Scarpecci, Mariangela Biava and Giovanna Poce
Pharmaceuticals 2020, 13(9), 227; https://doi.org/10.3390/ph13090227 - 31 Aug 2020
Cited by 11 | Viewed by 4792
Abstract
Tuberculosis remains the world’s top infectious killer: it caused a total of 1.5 million deaths and 10 million people fell ill with TB in 2018. Thanks to TB diagnosis and treatment, mortality has been falling in recent years, with an estimated 58 million [...] Read more.
Tuberculosis remains the world’s top infectious killer: it caused a total of 1.5 million deaths and 10 million people fell ill with TB in 2018. Thanks to TB diagnosis and treatment, mortality has been falling in recent years, with an estimated 58 million saved lives between 2000 and 2018. However, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains is a major concern that might reverse this progress. Therefore, the development of new drugs acting upon novel mechanisms of action is a high priority in the global health agenda. With the approval of bedaquiline, which targets mycobacterial energy production, and delamanid, which targets cell wall synthesis and energy production, the energy-metabolism in Mtb has received much attention in the last decade as a potential target to investigate and develop new antimycobacterial drugs. In this review, we describe potent anti-mycobacterial agents targeting the energy-metabolism at different steps with a special focus on structure-activity relationship (SAR) studies of the most advanced compound classes. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

17 pages, 538 KiB  
Review
Polymyxin Delivery Systems: Recent Advances and Challenges
by Natallia V. Dubashynskaya and Yury A. Skorik
Pharmaceuticals 2020, 13(5), 83; https://doi.org/10.3390/ph13050083 - 29 Apr 2020
Cited by 38 | Viewed by 5462
Abstract
Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin [...] Read more.
Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin delivery systems that improve polymyxin bioavailability and reduce drug toxicity through targeted and controlled release. Currently, the most suitable systems for improving oral, inhalation, and parenteral polymyxin delivery are polymer particles, liposomes, and conjugates, while gels, polymer fibers, and membranes are attractive materials for topical administration of polymyxin for the treatment of infected wounds and burns. In general, the application of these systems protects polymyxin molecules from the negative effects of both physiological and pathological factors while achieving higher concentrations at the target site and reducing dosage and toxicity. Improving the properties of polymyxin will be of great interest to researchers who are focused on developing antimicrobial drugs that show increased efficacy and safety. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-16
Back to TopTop