Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.6
4.6
Journals
Molecules
Special Issues
Chemical Design and Synthesis of Antimicrobial Drugs
molecules-logo
Submit to Special Issue Submit Abstract to Special Issue Review for Molecules Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Chemical Design and Synthesis of Antimicrobial Drugs

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 3906

Special Issue Editors

Dr. Ma Su

E-Mail Website
Guest Editor
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
Interests: drug discovery; medicinal chemistry; antimicrobial drugs; small-molecule inhibitors; peptidomimetics; stapled peptides
Dr. Diana I.S.P. Resende

E-Mail Website
Guest Editor
1. LQOF-Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
2. CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, 4450-208 Matosinhos, Portugal
3. ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua de Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
Interests: pharmaceuticals; chemical sciences; organic chemistry

Special Issue Information

Dear Colleagues,

The development of antimicrobial drugs with novel structures and clear mechanisms of action that are active against drug-resistant bacteria has become urgent; this is due to the rise of bacterial drug resistance and the need to safeguard human health. To combat antimicrobial resistance, the WHO published a list of “ESKAPE” pathogens that pose the greatest threat to human health in 2017; in order, these are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.

Researchers have thus attempted to uncover the mystery of bacterial resistance and develop more convenient and effective antibacterial strategies. This Special Issue provides up-to-date research and perspectives on the discovery, rational design, and chemical, pharmacological, in vitro and clinical properties of natural and synthetic antimicrobial agents, in order to understand the relationship between their molecular structure and biological activity or mode of action. The scope of this Special Issue includes the following:

The design, synthesis, and biological evaluation of novel biologically active antimicrobial compounds.

The molecular modification of reported series that lead to a significantly enhanced understanding of their structure–activity relationships (SAR).

Computational studies that provide fresh insight into the SAR of compound series that are of current general interest, or the analysis of other available data that subsequently advance medicinal chemistry knowledge.

The effect of the molecular structure on the distribution, pharmacokinetics, and metabolic transformation of biologically active compounds. This may include the design, synthesis, and evaluation of novel types of prodrugs.

Dr. Ma Su
Dr. Diana I.S.P. Resende
Guest Editors

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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • antimicrobial drugs
  • rational design
  • drug resistance
  • ESKAPE pathogens
  • structure–activity relationship
  • advanced skeleton

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 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

12 pages, 1833 KB  
Article
Targeting Bacterial Adenylate Kinase mRNA with a Chimeric Antisense Oligonucleotide for Rational Antibacterial Drug Development
by Lozena A. Otcheva, Martina Traykovska and Robert Penchovsky
Molecules 2025, 30(16), 3425; https://doi.org/10.3390/molecules30163425 - 20 Aug 2025
Viewed by 377
Abstract
Multi-drug resistance in human bacterial pathogens has become a significant challenge for global healthcare this century, mainly due to the widespread misuse of antibiotics worldwide. As a result, millions of people have been affected by multi-drug-resistant bacterial infections. The antibiotic development pipelines cannot [...] Read more.
Multi-drug resistance in human bacterial pathogens has become a significant challenge for global healthcare this century, mainly due to the widespread misuse of antibiotics worldwide. As a result, millions of people have been affected by multi-drug-resistant bacterial infections. The antibiotic development pipelines cannot cope with the need to produce new antibiotics. Therefore, more productive antibiotic development methods must be invented. This paper presents an entirely rational approach for antibacterial drug discovery based on chimeric antisense oligonucleotide targeting (ASO) of the adenylate kinase mRNA in Staphylococcus aureus. The ASO is delivered into the bacteria via the cell-penetrating oligopeptide pVEC. The pVEC-ASO1 exhibits a bactericidal effect against Staphylococcus aureus, with a 50% minimal inhibitory concentration of 500 nM. The pVEC-ASO1 has a 98% survivability rate at the same concentration on cell lines. These findings strongly suggest that this chimeric ASO is a promising antibacterial drug candidate. Moreover, this is the fifth bacterial mRNA we have successfully targeted with pVEC-ASOs, providing further evidence for the efficiency of our approach. In contrast to the previous four targets, riboswitches residing in the 5′-untranslated region, we target the coding part of mRNA found in bacteria. That suggests that our approach may have much broader therapeutic applications. Full article
(This article belongs to the Special Issue Chemical Design and Synthesis of Antimicrobial Drugs)
►▼ Show Figures

Figure 1

29 pages, 4810 KB  
Article
Olive Leaf Protein Hydrolysate as a Novel Source of Antimicrobial Peptides: Peptidomic Characterization and In Silico Evaluation
by Teresa Gonzalez-de la Rosa, Alonso Herreros-Isidro, Elvira Marquez-Paradas, Luna Barrera-Chamorro, Maria J. Leon and Sergio Montserrat-de la Paz
Molecules 2025, 30(16), 3382; https://doi.org/10.3390/molecules30163382 - 14 Aug 2025
Viewed by 460
Abstract
Olive (Olea europaea) leaves, a by-product of olive oil production, represent a promising source of bioactive peptides. In this study, the peptidome of an olive leaf protein hydrolysate (OLPH) obtained via enzymatic hydrolysis with Alcalase was identified and analyzed for the [...] Read more.
Olive (Olea europaea) leaves, a by-product of olive oil production, represent a promising source of bioactive peptides. In this study, the peptidome of an olive leaf protein hydrolysate (OLPH) obtained via enzymatic hydrolysis with Alcalase was identified and analyzed for the first time. Liquid Chromatography coupled to Trapped Ion Mobility Spectrometry and Tandem Mass Spectrometry (LC-TIMS-MS/MS) analysis revealed over 7000 peptide sequences. Peptides with PeptideRanker scores above 0.79 were selected for in silico evaluation of antimicrobial potential, including physicochemical characterization and molecular docking. Several peptides—such as NYPAWGY, SSKGSLGGGF, QWDQGYF, and SGPAFNAGR—exhibited strong predicted antimicrobial potential, supported by favorable interactions with bacterial, viral, and fungal targets in docking simulations. Correlation analysis revealed that physicochemical features, such as net hydrogen, amphipathicity, and isoelectric point, were positively associated with predicted antimicrobial activity. These findings highlight the potential of olive leaf-derived peptides as natural antimicrobial agents and support the valorization of olive by-products as a sustainable source of functional ingredients for applications in food safety and health. Further experimental validation is needed to confirm the efficacy and mechanism of action of the identified peptides. Full article
(This article belongs to the Special Issue Chemical Design and Synthesis of Antimicrobial Drugs)
►▼ Show Figures

Figure 1

25 pages, 3867 KB  
Article
Amino Acid Substitutions in Bacteriocin Lactolisterin BU Reveal Functional Domains Involved in Biological Activity Against Staphylococcus aureus
by Lazar Gardijan, Milka Malešević, Miroslav Dinić, Aleksandar Pavić, Nikola Plačkić, Goran Jovanović and Milan Kojić
Molecules 2025, 30(15), 3134; https://doi.org/10.3390/molecules30153134 - 26 Jul 2025
Viewed by 860
Abstract
The emergence of multidrug-resistant pathogens has driven the development of novel antimicrobial peptides (AMPs) as therapeutic alternatives. Lactolisterin LBU (LBU) is a bacteriocin with promising activity against Gram-positive bacteria, including Staphylococcus aureus. In this study, we designed and evaluated a panel of [...] Read more.
The emergence of multidrug-resistant pathogens has driven the development of novel antimicrobial peptides (AMPs) as therapeutic alternatives. Lactolisterin LBU (LBU) is a bacteriocin with promising activity against Gram-positive bacteria, including Staphylococcus aureus. In this study, we designed and evaluated a panel of amino acid variants of LBU to investigate domain–activity relationships and improve activity. Peptides were commercially synthesized, and their effect was evaluated for minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), hemolytic activity, cytotoxicity, in vivo toxicity, and virulence modulation. AlphaFold3 structural prediction of LBU revealed a four-helix topology with amphipathic and hydrophobic segments. Helical wheel projections identified helices I and IV as amphipathic, suggesting their potential involvement in membrane interaction and activity. Glycine-to-alanine substitutions at helix I markedly increased antimicrobial activity but altered toxicity profiles. In contrast, changes at helix junctions and kinks reduced antimicrobial activity. We also showed differential regulation of virulence genes upon sub-MIC treatment. Overall, rational substitution enabled identification of residues critical for activity and toxicity, providing insights into therapeutic tuning of lactolisterin-based peptides. Full article
(This article belongs to the Special Issue Chemical Design and Synthesis of Antimicrobial Drugs)
►▼ Show Figures

Figure 1

15 pages, 586 KB  
Article
Antifouling Properties of N,N′-Dialkylated Tetraazamacrocyclic Polyamines and Their Metal Complexes
by Mathieu Berchel, Dorsaf Malouch, Maryline Beyler, Maryline Fauchon, Yannick Toueix, Claire Hellio and Paul-Alain Jaffrès
Molecules 2025, 30(11), 2368; https://doi.org/10.3390/molecules30112368 - 29 May 2025
Cited by 1 | Viewed by 390
Abstract
The prevention of biofouling (biological fouling) became a major economic and environmental issue. In the present study, we designed a series of four cyclam and cyclen derivatives with a modulation of their lipophilicity by introducing either two benzyl (Bn) groups or two tetradecyl [...] Read more.
The prevention of biofouling (biological fouling) became a major economic and environmental issue. In the present study, we designed a series of four cyclam and cyclen derivatives with a modulation of their lipophilicity by introducing either two benzyl (Bn) groups or two tetradecyl (C14) chains in the structure to produce (Cyclam(Bn)2, Cyclam(C14)2, Cyclen(Bn)2 and Cyclen(C14)2). Additionally, copper (Cu) and zinc (Zn) complexes of each compound were prepared and evaluated as potential antifouling candidates against two models of Vibrio species (V. natriegens and V. aestuarianus). The results highlight that no significant antifouling activity was measured for the metal free polyazamacrocyclic derivatives. However, for the metal complexes, the nature of the cation (Cu2+ or Zn2+) modulates both the growth and adhesion capacities of the two bacteria. Overall, in most cases, Zn complexes showed better activity than the Cu complexes, revealing the importance of the metal cation. Moreover, in the cyclam series, the anti-adhesion properties could be linked to a biocidal effect while a full anti-adhesion activity was observed in the cyclen series. Full article
(This article belongs to the Special Issue Chemical Design and Synthesis of Antimicrobial Drugs)
►▼ Show Figures

Figure 1

22 pages, 5706 KB  
Article
Antibiofilm Activities of Tritrpticin Analogs Against Pathogenic Pseudomonas aeruginosa PA01 Strains
by Gopal Ramamourthy, Hiroaki Ishida and Hans J. Vogel
Molecules 2025, 30(4), 826; https://doi.org/10.3390/molecules30040826 - 11 Feb 2025
Viewed by 1035
Abstract
In our previous work, we showed that short antimicrobial hexapeptides (AMPs) containing three Trp and three Arg residues had a potent antibiofilm activity against a pathogenic Gram-positive Staphylococcus aureus MRSA strain. However, the activity of these hexapeptides against a Gram-negative Pseudomonas aeruginosa PA01 [...] Read more.
In our previous work, we showed that short antimicrobial hexapeptides (AMPs) containing three Trp and three Arg residues had a potent antibiofilm activity against a pathogenic Gram-positive Staphylococcus aureus MRSA strain. However, the activity of these hexapeptides against a Gram-negative Pseudomonas aeruginosa PA01 strain was relatively poor. Herein, we tested the longer 13-residue synthetic AMP tritrpticin-NH2 (Tritrp) and several of its analogs as potential antibiofilm agents that can prevent biofilm formation (MBIC) and/or cause biofilm dissolution (MBEC) for two P. aeruginosa PA01 strains, one of which expressed the GFP protein. Tritrp, a porcine cathelicidin, is currently the only known naturally occurring cationic AMP that has three Trp in sequence (WWW), a feature that was found to be important in our previous study. Our results show that several Tritrp analogs were effective. In particular, analogs with Pro substitutions that had altered peptide backbone structures compared to the naturally occurring amphipathic two-turn structure showed more potent MBIC and MBEC antibiofilm activities. Selectivity of the peptides towards P. aeruginosa could be improved by introducing the non-proteinogenic amino acid 2,3-diaminopropionic acid, rather than Arg or Lys, as the positively charged residues. Using 1H NMR spectroscopy, we also reinvestigated the role of the two Pro residues in cis–trans isomerism of the peptide in aqueous solution. Overall, our results show that the WWW motif embedded in longer cationic AMPs has considerable potential to combat biofilm formation in pathogenic Gram-negative strains. Full article
(This article belongs to the Special Issue Chemical Design and Synthesis of Antimicrobial Drugs)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop