Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.7
4.6
Journals
Antibiotics
Special Issues
Strategies for the Design of Hybrid-Based Antimicrobial Compounds
share announcement

Strategies for the Design of Hybrid-Based Antimicrobial Compounds

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 2433

Special Issue Editors

Dr. Vuyolwethu Khwaza

E-Mail Website
Guest Editor
Department of Chemistry, Faculty of Science and Agriculture, University of Fort Hare, Alice 5700, South Africa
Interests: natural product chemistry; organic synthesis; hybrid compounds; antimicrobial compounds; anticancer compounds; phytochemicals and their derivatives; medicinal chemistry
Dr. Sibusiso Alven

E-Mail Website
Guest Editor
Department of Chemistry, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6001, South Africa
Interests: polymers; nanoparticles; wound dressings; skin regeneration; nanofibers; membranes; hydrogels; essential oils; anticancer drugs; antimalarials
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Blessing Atim Aderibigbe

E-Mail Website
Guest Editor
Department of Chemistry, Tarleton State University, Stephenville, TX, USA
Interests: polymer-based materials; wound dressings; drug delivery systems; nanocarriers; drug discovery and design; organic synthesis of drug molecules (antimalarials, antimicrobials, anticancer)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rising threat of multidrug-resistant (MDR) pathogens. In the design of antimicrobial drugs, hybrid molecules containing two or more pharmacophores have emerged as a promising drug design strategy to overcome the issue of MDR. These hybrid molecules display high potential to offer better pharmacokinetic characteristics, suppress resistance mechanisms, and enhance therapeutic outcomes.

The aim of this Special Issue is to provide a platform for researchers working on the synthesis, pharmacological evaluation, and mechanistic investigations of synthetic or plant-based hybrid antimicrobial drugs to publish their findings. Authors are invited to contribute their original research articles, reviews, and communications focusing on innovative hybrid molecules targeting bacterial, fungal, and viral infections.

Dr. Vuyolwethu Khwaza
Dr. Sibusiso Alven
Prof. Dr. Blessing Atim Aderibigbe
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 250 words) can be sent to the Editorial Office for assessment.

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. Antibiotics 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

  • hybrid compounds
  • antimicrobial agents
  • antibacterial agents
  • antifungal activity
  • antiviral activity
  • in vitro evaluation
  • structure–activity relationship (SAR)
  • bioactive molecules
  • nanoformulations
  • targeted drug delivery
  • pharmacological screening
  • clinical studies

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 (3 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

28 pages, 3550 KB  
Article
Synthesis, Characterization, Antimicrobial Activity and Molecular Modeling Studies of Novel Indazole-Benzimidazole Hybrids
by Redouane Er-raqioui, Sara Roudani, Imane El Houssni, Njabulo J. Gumede, Yusuf Sert, Ricardo F. Mendes, Dimitry Chernyshov, Filipe A. A. Paz, José A. S. Cavaleiro, Maria do Amparo F. Faustino, Rakib El Mostapha, Said Abouricha, Khalid Karrouchi, Maria da Graça P. M. S. Neves and Nuno M. M. Moura
Antibiotics 2025, 14(11), 1150; https://doi.org/10.3390/antibiotics14111150 - 13 Nov 2025
Viewed by 412
Abstract
Background/Objectives: In this work, a series of six new indazole-benzimidazole hybrids (M1–M6) were designed, synthesized, and fully characterized. The design of these compounds was based on the combination of two pharmacophoric units, indazole and benzimidazole, both known for [...] Read more.
Background/Objectives: In this work, a series of six new indazole-benzimidazole hybrids (M1–M6) were designed, synthesized, and fully characterized. The design of these compounds was based on the combination of two pharmacophoric units, indazole and benzimidazole, both known for their broad spectrum of biological activities. Methods: The molecular hybridization strategy was planned to combine these scaffolds through an effective synthetic pathway, using 6-nitroindazole, two 2-mercaptobenzimidazoles, and 1,3- or 1,5-dihaloalkanes as key precursors, affording the desired hybrids in good yields and with enhanced biological activity. Quantum chemical calculations were performed to investigate the structural, electronic, and electrostatic properties of M1–M6 molecules using Density Functional Theory (DFT) at the B3LYP/6-311++G(d,p) level. The antimicrobial activity efficacy of these compounds was assessed in vitro against four Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, and Lactobacillus plantarum), four Gram-negative bacteria (Salmonella enteritidis, Escherichia coli, Campylobacter coli, Campylobacter jejuni), and four fungal strains (Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, and Candida glabrata) using ampicillin and tetracycline as reference standard drugs. Results: Among the series, compound M6 exhibited remarkable antimicrobial activity, with minimum inhibitory concentrations (MIC) of 1.95 µg/mL against S. cerevisiae and C. tropicalis, and 3.90 µg/mL against S. aureus, B. cereus, and S. enteritidis, while the standards Ampicillin (AmB) (MIC ≥ 15.62 µg/mL) and Tetracycline (TET) (MIC ≥ 7.81 µg/mL) exhibited higher MIC values. To gain molecular insights into the compounds, an in silico docking study was performed to determine the interactions of M1–M6 ligands against the antimicrobial target beta-ketoacyl-acyl carrier protein (ACP) synthase III complexed with malonyl-COA (PDB ID: 1HNJ). Molecular modeling data provided valuable information on the structure-activity relationship (SAR) and the binding modes influencing the candidate ligand-protein recognition. Amino acid residues, such as Arg249, located in the solvent-exposed region, were essential for hydrogen bonding with the nitro group of the 6-nitroindazole moiety. Furthermore, polar side chains such as Asn274, Asn247, and His244 participated in interactions mediated by hydrogen bonding with the 5-nitrobenzimidazole moiety of these compound series. Conclusions: The hybridization of indazole and benzimidazole scaffolds produced compounds with promising antimicrobial activity, particularly M6, which demonstrated superior potency compared to standard antibiotics. Computational and docking analyses provided insights into the structure–activity relationships, highlighting these hybrids as potential candidates for antimicrobial drug development. Full article
(This article belongs to the Special Issue Strategies for the Design of Hybrid-Based Antimicrobial Compounds)
►▼ Show Figures

Graphical abstract

23 pages, 506 KB  
Article
Design and Synthesis of Hybrid Compounds for Potential Treatment of Bacterial Co-Infections: In Vitro Antibacterial and In Silico Studies
by Vuyolwethu Khwaza, Opeoluwa O. Oyedeji, Eric Morifi, Mutshinyalo Nwamadi, Thierry Youmbi Fonkui, Derek Tantoh Ndinteh and Blessing A. Aderibigbe
Antibiotics 2025, 14(6), 582; https://doi.org/10.3390/antibiotics14060582 - 6 Jun 2025
Cited by 3 | Viewed by 1612
Abstract
Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and [...] Read more.
Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and overcome resistance mechanisms. The synthesized compounds were evaluated for their antibacterial activity against five Gram-negative and seven Gram-positive bacterial strains. In silico pharmacokinetic and drug-likeness properties of selected active compounds (12–16, 19, 21, and 23) were predicted using the SwissADME web tool. Results: Compounds 12–16, 19, 21, and 23 demonstrated significant antibacterial activity, with compound 16 (a ciprofloxacin-containing hybrid) exhibiting the most potent effect, showing a minimum inhibitory concentration (MIC) of 7.8125 µg/mL against all tested bacterial strains. The in silico analysis revealed favorable pharmacokinetic profiles, drug-likeness, lipophilicity, and water solubility of most hybrid compounds. Discussion: The synthesized hybrid compounds exhibited enhanced antibacterial activity and desirable pharmacokinetic properties, particularly compound 16. These findings suggest the potential of these molecules in combating bacterial pathogens, especially those implicated in co-infections in COVID-19 infections. Conclusions: The study presents promising hybrid antibacterial agents with potential application as adjunct therapies for treating COVID-19-associated bacterial co-infections. Further investigation is needed, which may lead to effective treatments for managing secondary bacterial infections in viral disease contexts. Full article
(This article belongs to the Special Issue Strategies for the Design of Hybrid-Based Antimicrobial Compounds)
►▼ Show Figures

Figure 1

Review

Jump to: Research

33 pages, 3252 KB  
Review
Recent Developments on Coumarin Hybrids as Antimicrobial Agents
by Sijongesonke Peter and Lunga Linda Sibali
Antibiotics 2025, 14(12), 1226; https://doi.org/10.3390/antibiotics14121226 - 5 Dec 2025
Abstract
Introduction: Globally, microbial infections are projected to be among the leading causes of death by 2050 due to rising drug resistance. Antimicrobials are vital for treating both animals and humans worldwide. However, their overuse and misuse accelerate drug resistance, posing a serious [...] Read more.
Introduction: Globally, microbial infections are projected to be among the leading causes of death by 2050 due to rising drug resistance. Antimicrobials are vital for treating both animals and humans worldwide. However, their overuse and misuse accelerate drug resistance, posing a serious threat to public health. Coumarin is a naturally occurring compound contributing health-beneficial features in drug discovery. Its high solubility in organic solvents, high bioavailability, simple structure, low toxicity, and low molecular weight make it an ideal candidate for combining with other pharmacophores to develop new therapeutic agents. This compound exhibits several biological activities, including antimicrobial, anticancer, anti-inflammatory, antidiabetic, neuroprotective, and anticoagulant effects, motivating medicinal researchers to hybridize it with other compounds to enhance its pharmacological efficacy. Hybridization of different pharmacophores via suitable linkers, including cleavable and non-cleavable ones, is a promising approach in drug development, resulting in new therapeutics with improved biological activity. Therefore, the hybridization of coumarin with other pharmacophores has become an interesting paradigm for medicinal scientists. Aim: This review aims to summarize the existing scientific literature on coumarin-based hybrid compounds with antimicrobial capabilities and discuss the structure–activity relationship (SAR) of these hybrids to potentially guide future research on and development of coumarin-based drugs for microbial treatment. Material and Methods: The review focuses on open-access literature about coumarin hybrid drugs available through searching tools such as Google, Google Scholar, ScienceDirect, and Scopus, published from 2024 to 2025. Results: Coumarin hybrids exhibit promising antimicrobial activity, particularly against S. aureus and C. albicans. The SAR reveals that halogenation, bulky aromatics, nitro, and hydroxyl groups enhance the interaction of the coumarin rings with amino acid residues. Conclusions: The reported coumarin hybrids showed a promising antimicrobial activity, with structural modifications influencing their activity. Hence, more studies, including more pre-clinical and clinical evaluations, are recommended for these hybrid compounds. Full article
(This article belongs to the Special Issue Strategies for the Design of Hybrid-Based Antimicrobial Compounds)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop