Plant Metabolites and Their Synthetic Derivatives as Potential Candidates for the Development of Drugs

A special issue of Plants (ISSN 2223-7747).

Deadline for manuscript submissions: 31 July 2026 | Viewed by 1784

Special Issue Editors


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Guest Editor
Fine Chemicals and Natural Products Laboratory, CIDIE CONICET-Universidad Católica de Córdoba, Córdoba, Argentina
Interests: plant-derived products; antibacterial activity; anticancer activity; enzyme inhibitors; inhibitors of MDR efflux pumps; bioguided isolation
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Special Issue Information

Dear Colleagues,

Since ancient times, plant-derived products have been used as traditional medicines, becoming an essential source of drugs. The significant potential of plants, the majority of which remains unexplored, for providing new active chemical entities encourages scientists to continue researching them. These structures could become promising scaffolds to inspire the design and development of novel therapeutic leads able to enrich libraries to be used in drug discovery pipelines.

This Special Issue intends to collect cutting-edge research and review works illustrating the potential of plant products to reflect upon the approaches of such drug discoveries and bring together organic chemists, pharmacognocists, pharmacologists, toxicologists, biologists, artificial intelligence experts, computer-aided drug design scientists, and clinicians working as a multidisciplinary team in the area of natural products.

We do hope that this Special Issue will provide extensive and applied knowledge of interest to scientists, such that they contribute to finding new avenues to develop potential therapeutic agents of natural origin against diseases.

Potential topics include but are not limited to the following:

  • Characterization of compounds obtained from plants with activity against pathogenic microorganisms, enzymes, or cancer;
  • In vitro screening of an important number of plant extracts with activity against pathogenic microorganisms, enzymes, or cancer;
  • In vivo models for testing plant-derived products with activity against pathogenic microorganisms, enzymes, or cancer;
  • Mechanisms of action of plant-derived compounds active against pathogenic microorganisms, enzymes, or cancer;
  • Computer-aided drug design (CADD) as a virtual tool for the screening and prediction of bioactive compounds;
  • Evaluation of synergy among bioactive chemical compounds (plant-derived and synthetic);
  • Synthetic derivatives of bioactive plant-derived compounds accompanied by their biological evaluation data and corresponding structure–activity relationship studies (SARSs).

Prof. Dr. María Cecilia Carpinella
Prof. Dr. Constantinos Athanassopoulos
Guest Editors

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Keywords

  • plant extracts
  • plant-derived compounds
  • biological activity
  • antibacterial activity
  • drugs development
  • synthetic natural product derivatives
  • multidrug resistance

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Published Papers (2 papers)

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Research

19 pages, 4339 KB  
Article
Cytotoxic Potential Evaluation of Innovative Pressurised Cyclic Solid–Liquid Extracts from Withania somnifera
by Rosanna Culurciello, Karen Power, Sergio Esposito, Ilaria Di Nardo, Simone Landi, Gionata De Vico, Domenico Palatucci, Elio Pizzo, Daniele Naviglio and Armando Zarrelli
Plants 2026, 15(7), 1027; https://doi.org/10.3390/plants15071027 - 26 Mar 2026
Viewed by 558
Abstract
Ethnopharmacological relevance. Withania somnifera (L.) Dunal, widely used in traditional medical systems such as Ayurveda, Unani, and Middle Eastern folk medicine, is valued for its adaptogenic, anti-inflammatory, neuroprotective, antimicrobial, and anticancer properties. These activities are primarily attributed to withanolides, with Withaferin A recognized [...] Read more.
Ethnopharmacological relevance. Withania somnifera (L.) Dunal, widely used in traditional medical systems such as Ayurveda, Unani, and Middle Eastern folk medicine, is valued for its adaptogenic, anti-inflammatory, neuroprotective, antimicrobial, and anticancer properties. These activities are primarily attributed to withanolides, with Withaferin A recognized as one of the most bioactive constituents. Although traditional preparations often rely on the root, leaf use provides a more sustainable alternative and may yield significant quantities of active metabolites. Identifying efficient, modern extraction technologies that can enhance the recovery of bioactive compounds from leaves is essential for developing effective, standardized ethnopharmacological formulations. Materials and methods. Plants of W. somnifera grown from seeds were subjected to different environmental conditions (control, drought, cold, yeast extract treatment). Leaves were extracted using Pressurized Cyclic Solid–Liquid Extraction (PCSLE) with hydroalcoholic solvents and compared with conventional infusion of dried leaves. Extracts were fractionated with solvents of varying polarity and analyzed by TLC, HPLC, and NMR for quantification of Withaferin A. Expression levels of key withanolide-biosynthetic genes (CAS, SMT1, DWARF1, CYP71, CYP76) were assessed using qRT-PCR. Antimicrobial activity of pure Withaferin A, aqueous extract, and hydroalcoholic PCSLE extract was evaluated through MIC and MBC assays against Gram-positive and Gram-negative strains. Cytotoxic activity was measured via MTT assays in six human cancer cell lines after 3, 6, and 24 h of treatment. Results. PCSLE yielded substantially higher levels of Withaferin A than traditional infusion, especially in medium-polarity fractions (chloroform and ethyl acetate), with concentrations reaching 0.70% in fresh leaf mass (4.8% dry weight), compared to 0.11% obtained by infusion. Gene expression analysis revealed that 24-week-old plants exhibited the highest transcription of withanolide-biosynthetic genes, and drought stress significantly upregulated CAS, SMT1, DWARF1, CYP71, and CYP716, indicating enhanced metabolic flux toward withanolide production. Hydroalcoholic PCSLE extracts showed broad-spectrum antimicrobial activity, with MIC and MBC values comparable to pure Withaferin A and demonstrating bactericidal effects against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. The aqueous extract showed activity only against Gram-positive strains. Cytotoxicity assays demonstrated an optimistic, dose-dependent reduction in cell viability across all tumour cell lines treated with the hydroalcoholic PCSLE extract, closely mirroring the activity of pure Withaferin A and consistently exceeding the effect of the aqueous extract. IC50 values confirmed the high bioactive content of PCSLE extracts and suggested mechanisms like those known for Withaferin A. Conclusions. PCSLE proved to be a highly efficient extraction technology for obtaining leaf extracts rich in Withaferin A, outperforming conventional extraction methods while exploiting sustainable plant tissue. Developmental stage and drought stress significantly modulated the expression of genes involved in withanolide biosynthesis, highlighting agronomic strategies capable of enhancing metabolite production. Hydroalcoholic PCSLE extracts exhibited antimicrobial and cytotoxic activities comparable to pure Withaferin A, supporting their relevance as promising therapeutic candidates. These findings advocate for the use of W. somnifera leaves as a sustainable source of bioactive compounds and demonstrate that advanced extraction technologies can contribute to the development of innovative ethnopharmacological preparations for antimicrobial and anticancer applications. Full article
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19 pages, 2740 KB  
Article
Antiproliferative Effects of Polar Extracts of the Aerial Parts of Fuchsia standishii J. Harrison
by María I. Ramírez, Aday González-Bakker, Adam N. Khan, Adrián Puerta and José M. Padrón
Plants 2025, 14(24), 3779; https://doi.org/10.3390/plants14243779 - 11 Dec 2025
Viewed by 824
Abstract
Fuchsia standishii J.Harrison is a species widely used in traditional medicine in southern Ecuador for treating various ailments, including high blood pressure, as an antacid and a relaxant. The pharmacological basis for these traditional uses is unknown. Given the reported anti-inflammatory and cytotoxic [...] Read more.
Fuchsia standishii J.Harrison is a species widely used in traditional medicine in southern Ecuador for treating various ailments, including high blood pressure, as an antacid and a relaxant. The pharmacological basis for these traditional uses is unknown. Given the reported anti-inflammatory and cytotoxic properties of the Onagraceae family, we investigated the plant’s potential for addressing chronic conditions. This study explored the bioactive potential of polar extracts from the aerial parts of F. standishii, focusing on antiproliferative activity against a panel of human tumor cell lines (A549, HBL-100, HeLa, SW1573, T-47D). The plant material was sequentially extracted and partitioned into nine fractions. All fractions were screened for antiproliferative activity, and the most active fractions were further evaluated for their mechanism of cell death (apoptosis/necrosis), genotoxicity, and induction of oxidative stress. Specialized metabolites in the fractions were characterized using UHPLC-DAD-MS3 analysis. F. standishii extracts showed potent antiproliferative activity. The dichloromethane fraction (MWD) was the most active (GI50 range: 8.5–39 µg/mL), demonstrating the ability to induce apoptosis in tumor cells and cause genotoxic damage linked to oxidative stress. The UHPLC-DAD-MS3 analysis successfully characterized the specialized metabolites present in the active fractions. The initial aqueous extract yielded a total of 47 secondary metabolites, 15 of which remained unassigned. F. standishii possesses a promising pharmacological profile that extends beyond its documented traditional uses. The MWD fraction represents a plausible source of novel anti-cancer agents due to its ability to induce apoptosis, supporting further bioguided investigation of this ethnobotanically relevant species. Full article
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