Bioactive Compounds as Therapeutic Leads: From Natural Sources to Mechanisms and Translation

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 818

Editors


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Guest Editor
Instituto de Saúde de Nova Friburgo, Universidade Federal Fluminense, Nova Friburgo, Brazil
Interests: natural products; cancer drugs; biological activity assays; chemotherapeutics; molecular targets
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Niterói 24020-141, RJ, Brazil
Interests: natural bioactive compounds; flavonoids and isoflavones; isolation and purification
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bioactive compounds derived from natural sources, including plants, marine organisms, fungi, and microorganisms, have long served as a cornerstone of drug discovery and a rich reservoir of chemical diversity for therapeutic innovation. Polyphenols, alkaloids, terpenoids, flavonoids, isoflavones, peptides, and many other secondary metabolites display a remarkable range of biological and pharmacological activities, encompassing antioxidants, anti-inflammatory, antimicrobial, antitumor, neuroprotective, cardioprotective, and metabolic effects. Recent advances in preclinical and clinical research have reinforced their promise in the prevention and treatment of complex diseases such as cancer, cardiovascular and neurodegenerative disorders, metabolic syndromes, and infectious diseases. Nevertheless, translating these compounds into effective and approved therapeutics remains a major challenge, requiring deeper mechanistic understanding, robust pharmacokinetic and pharmacodynamic profiling, innovative formulation and delivery strategies, and rigorous clinical validation.

This Special Issue aims to provide a comprehensive platform for advancing the understanding of bioactive compounds as therapeutic leads, bridging natural product chemistry, mechanistic biology, pharmacology, and translational medicine. Aligned with the scope of Biomedicines, we welcome contributions addressing the discovery, isolation, structural characterization, and biological evaluation of naturally derived molecules, as well as their development into candidate therapeutics. The collection will highlight both experimental and clinical evidence, foster cross-disciplinary dialogue between chemists, biologists, pharmacologists, and clinicians, and pave the way for novel therapeutic strategies grounded in bioactive natural compounds.

For this Special Issue, original research articles and review papers are welcome. Research areas may include, but are not limited to, the following:

  • Natural sources, biosynthesis, isolation, and chemical characterization of bioactive compounds;
  • Structural elucidation, structure–activity relationships (SAR), and medicinal chemistry of natural leads;
  • Molecular mechanisms of action, including modulation of signaling pathways, apoptosis, oxidative stress, and inflammation;
  • Bioactive compounds in cancer biology, cardiovascular health, neuroprotection, and metabolic regulation;
  • Antimicrobial, antiviral, antiparasitic, and immunomodulatory activities of natural products;
  • Novel drug delivery systems, nanoformulations, and bioavailability enhancement strategies;
  • Preclinical models, pharmacokinetics, and translational studies of bioactive compounds;
  • Clinical evidence, safety profiles, and therapeutic applications of natural-product-derived agents;
  • Synergistic effects of bioactive compounds with conventional drugs or other natural molecules;
  • Computational approaches, in silico screening, and AI-driven discovery of natural therapeutic leads.

We look forward to receiving your valuable contributions to this Special Issue.

Dr. Bruno Kaufmann Robbs
Prof. Dr. Lucas Silva Abreu
Guest Editors

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Keywords

  • bioactive compounds
  • natural products
  • therapeutic leads
  • drug discovery
  • mechanisms of action
  • translational medicine
  • phytochemicals
  • flavonoids and isoflavones
  • pharmacological activity
  • natural-product-based therapeutics

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Published Papers (1 paper)

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Research

16 pages, 3248 KB  
Article
Discovery of a Novel 4,5-Dihydro-1H-pyrazole-1-carbothioamide Derivative with Cytotoxic, Apoptotic, and ABL1 Inhibitory Activities Against Chronic Myeloid Leukemia
by Ayben Erkan, Ayca Irgit Calayir, Halilibrahim Ciftci and Belgin Sever
Biomedicines 2026, 14(7), 1651; https://doi.org/10.3390/biomedicines14071651 - 22 Jul 2026
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Abstract
Background/Objectives: Chronic myeloid leukemia (CML) is a hematological malignancy driven by the constitutively active BCR-ABL1 fusion protein. Although current ABL1 tyrosine kinase inhibitors (TKIs) have improved CML management, resistance remains a major challenge, highlighting the need for novel therapeutic strategies. Methods: [...] Read more.
Background/Objectives: Chronic myeloid leukemia (CML) is a hematological malignancy driven by the constitutively active BCR-ABL1 fusion protein. Although current ABL1 tyrosine kinase inhibitors (TKIs) have improved CML management, resistance remains a major challenge, highlighting the need for novel therapeutic strategies. Methods: A chalcone derivative containing naphthalene and toluene moieties (A) was synthesized from 2-acetonaphthone and p-tolualdehyde and subsequently converted into a novel 4,5-dihydro-1H-pyrazole-1-carbothioamide derivative (B) through reaction with thiosemicarbazide. The cytotoxicity of compounds A and B against K562 CML cells was evaluated using the MTT assay. The active compound was further investigated for cytotoxic selectivity using HL-60 acute myeloid leukemia (AML) cells and healthy PBMCs. Apoptotic effects in K562 cells were analyzed using Annexin V/ethidium homodimer staining, whereas ABL1 inhibitory activity was determined using the ADP-Glo kinase assay. The potential interaction between the active compound and ABL1 was assessed by molecular docking analysis. Results: Compound B displayed potent cytotoxic activity against K562 cells with an IC50 value of 6.92 ± 1.14 µM and demonstrated selectivity toward leukemic cells over PBMCs (SI = 5.4). Treatment with compound B markedly induced apoptosis in K562 cells. In addition, compound B inhibited ABL1 activity in a concentration-dependent manner. Molecular docking studies revealed a favorable binding orientation within the ATP-binding pocket of ABL1. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) analysis predicted favorable pharmacokinetic properties for compound B. Conclusions: These findings demonstrate that compound B possesses cytotoxic, pro-apoptotic, and ABL1 inhibitory activities against CML cells and may serve as a promising lead structure for the development of novel therapeutic agents targeting CML. Full article
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