Antimicrobial and Anticancer Scaffolds in Medicinal Chemistry

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

Deadline for manuscript submissions: 30 November 2026 | Viewed by 1795

Editor


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Guest Editor
Independent Radiopharmacy Unit, Faculty of Pharmacy, Medical University of Lublin, 20-093 Lublin, Poland
Interests: medicinal chemistry; organic synthesis; heterocycles; anticancer activity; antimicrobial activity; SAR
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Special Issue Information

Dear Colleagues,

Modern medicinal chemistry plays a key role in the design and synthesis of compounds with antibacterial and anticancer activity. These systems are often based on heterocyclic structures, transition metal complexes, and natural compounds and their analogues. In the field of anticancer therapy, particular attention is paid to compounds targeting specific signaling pathways in cancer cells, such as tyrosine kinase inhibitors and apoptotic protein modulators. In turn, to combat bacterial resistance, new classes of antibiotics, antimicrobial peptides, and drug delivery systems, such as nanocarriers, are being developed. The integration of computational chemistry, molecular biology, and materials technology enables the synthesis of new compounds and the creation of more selective and effective therapies. A review of current trends indicates the growing importance of targeted therapies and personalized medicine in the treatment of infections and cancer. We invite submissions of original articles, reviews, analyses, studies, and reports under this topic.

Prof. Dr. Monika Pitucha
Guest Editor

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Keywords

  • antimicrobial
  • anticancer
  • synthesis
  • complex
  • organic compounds
  • heterocyclic compounds
  • SAR

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Published Papers (2 papers)

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Research

36 pages, 4054 KB  
Article
Multifunctional Curcumin-Inspired 3,5-Diarylidene-4-Piperidones: Design, Synthesis, Biological Evaluation and Computational Mechanistic Studies
by Angel K. Nkosi, Adel S. Girgis, Ahmed Samir, Mohamed A. Morsy, Amira M. Shaban, Walid Fayad, Ahmed A. F. Soliman, Christine T. Williams, Shogo Mori, Leena Khanna, Guido F. Verbeck and Siva S. Panda
Pharmaceuticals 2026, 19(6), 935; https://doi.org/10.3390/ph19060935 - 13 Jun 2026
Viewed by 467
Abstract
Background/Objectives: Antimicrobial resistance and bacterial persistence underscore the need to develop new chemotypes with multifunctional antibacterial mechanisms. This study aimed to design, synthesize, and evaluate curcumin-inspired 3,5-diarylidene-4-piperidones as versatile small molecules exhibiting antibacterial, antibiofilm, anti-efflux, DNA gyrase-inhibitory, and antiproliferative properties. Methods: A targeted [...] Read more.
Background/Objectives: Antimicrobial resistance and bacterial persistence underscore the need to develop new chemotypes with multifunctional antibacterial mechanisms. This study aimed to design, synthesize, and evaluate curcumin-inspired 3,5-diarylidene-4-piperidones as versatile small molecules exhibiting antibacterial, antibiofilm, anti-efflux, DNA gyrase-inhibitory, and antiproliferative properties. Methods: A targeted series of triazole-conjugated 3,5-diarylidene-4-piperidones was synthesized through copper-catalyzed azide-alkyne cycloaddition click chemistry and subsequently characterized using standard spectroscopic techniques. The compounds were assessed for antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. Selected active compounds underwent further evaluation for DNA gyrase inhibition, antibiofilm activity against multidrug-resistant S. aureus ATCC 33591, ethidium bromide accumulation, and antiproliferative effects on HCT116 and MCF7 cancer cells, with RPE1 cells serving as a control to evaluate cytotoxicity in normal cells. Additionally, computational studies, including QSAR analysis and molecular docking, were conducted to bolster structure–activity relationships and provide mechanistic insights. Results: Several derivatives demonstrated selective antibacterial activity against Gram-positive bacteria, particularly S. aureus, while exhibiting limited or no efficacy against E. coli. Compounds 7n and 7l emerged as the most potent against S. aureus, with minimum inhibitory concentrations (MICs) of 7.8 and 8.2 μM, respectively. Notably, compound 7l inhibited S. aureus DNA gyrase supercoiling, displaying an IC50 of 3.20 μM, comparable to ciprofloxacin. Compound 7e exhibited the strongest antibiofilm activity against multidrug-resistant S. aureus, whereas compound 7a resulted in the highest accumulation of ethidium bromide, indicating robust anti-efflux activity. Antiproliferative assays revealed that select halogenated derivatives were effective against HCT116 and MCF7 cells, while the most promising antibacterial compounds exhibited minimal cytotoxicity toward RPE1 cells. Quantitative structure–activity relationship (QSAR) and docking studies supported the observed structure–activity relationships and suggested potential interactions with the ATPase binding site of DNA gyrase B. Conclusions: Triazole-conjugated 3,5-diarylidene-4-piperidones are promising multifunctional scaffolds with selective anti-S. aureus activity, antibiofilm and anti-efflux properties, and, for compound 7l, potent DNA gyrase inhibition. These findings support further optimization of this chemotype as a platform for developing antibacterial agents with polymechanistic activity. Full article
(This article belongs to the Special Issue Antimicrobial and Anticancer Scaffolds in Medicinal Chemistry)
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19 pages, 2948 KB  
Article
Reinvestigating Pyrrol-2-One-Based Compounds: From Antimicrobial Agents to Promising Antitumor Candidates
by Natalia Simionescu, Ashraf Al-Matarneh, Ionel I. Mangalagiu, Narcis Cibotariu, Cristina Mariana Uritu, Cristina Maria Al-Matarneh and Mariana Pinteala
Pharmaceuticals 2025, 18(12), 1813; https://doi.org/10.3390/ph18121813 - 27 Nov 2025
Cited by 1 | Viewed by 879
Abstract
Background: Heteroaromatic iodine-containing compounds have been previously recognized for their broad-spectrum antimicrobial activity. This study aims to systematically investigate their potential repurposing as anticancer agents, with a particular focus on understanding the structural determinants that influence their cytotoxicity and selectivity toward malignant cells. [...] Read more.
Background: Heteroaromatic iodine-containing compounds have been previously recognized for their broad-spectrum antimicrobial activity. This study aims to systematically investigate their potential repurposing as anticancer agents, with a particular focus on understanding the structural determinants that influence their cytotoxicity and selectivity toward malignant cells. Methods: A series of heteroaromatic iodine-containing derivatives were synthesized and evaluated for anticancer activity. Their cytotoxic effects were measured and compared between cancerous and normal cell lines to determine selectivity. Structural features, including heteroaromatic moieties and substituents, were analyzed to identify correlations with biological activity. Results: Among the tested compounds, derivatives 3e, 3g, and 3l demonstrated significant cytotoxic effects while exhibiting favorable selectivity indices. These findings indicate that these compounds preferentially target malignant cells over normal cells, thereby mitigating the issue of systemic toxicity often associated with traditional chemotherapeutics. The enhanced anticancer activity appears to be influenced by specific structural elements within the heteroaromatic framework. Conclusions: The study highlights the potential of heteroaromatic iodine-containing compounds as promising anticancer candidates. Rational structural modifications within these heterocyclic systems can effectively modulate bioactivity and improve therapeutic selectivity. These results support further development of this compound class for anticancer applications. Full article
(This article belongs to the Special Issue Antimicrobial and Anticancer Scaffolds in Medicinal Chemistry)
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