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Molecules

Molecules is a leading international, peer-reviewed, open access journal of chemistry published semimonthly online by MDPI.
Indexed in PubMed | Quartile Ranking JCR - Q2 (Biochemistry and Molecular Biology | Chemistry, Multidisciplinary)

All Articles (62,545)

Chemotherapy resistance in colorectal cancer (CRC) represents a critical clinical challenge leading to treatment failure and poor patient prognosis. Artemisinin is a natural product isolated from Artemisia annua, and its clinically relevant derivatives include dihydroartemisinin (DHA) and artesunate. Beyond their established antimalarial efficacy, both artemisinin and its derivatives—collectively referred to as artemisinin-derived compounds (ADs)—have been increasingly recognized for their unique potential to reverse multidrug resistance in cancer. Unlike previous reviews focusing on isolated mechanisms, this review systematically constructs a multidimensional, synergistic attack network centered on ADs to elucidate their integrated actions against chemotherapy-resistant CRC. Mechanistically, ADs suppress cancer stem cell (CSC)-associated resistance phenotypes while concurrently reshaping the tumor immune microenvironment, highlighting a functional coupling between stemness inhibition and immune remodeling. In parallel, this review presents apoptosis reactivation and ferroptosis induction as complementary, dual-track cell death strategies that collectively circumvent apoptosis resistance. Moreover, ADs exert “one-strike–multiple-effects” through coordinated regulation of pro-survival signaling networks and immune-related pathways, including the induction of immunogenic cell death (ICD) and the modulation of immunosuppressive macrophage subsets. Beyond mechanistic insights, this review integrates emerging translational considerations, including clinical pharmacokinetics, safety and tolerability, formulation and delivery strategies, and rational combination therapy paradigms in CRC. Collectively, these findings position ADs as multi-dimensional modulators rather than a single-agent cytotoxic, providing a coherent mechanistic and translational rationale for their further development in chemotherapy-resistant CRC.

11 January 2026

Chemical Structures of Artemisinin, Dihydroartemisinin, and Artesunate, Illustrating Their Metabolic and Semi-synthetic Relationships. (a) The Structure of Artemisinin, (b) The Structure of Dihydroartemisinin, (c) The Structure of Artesunate.

Atractylenolides (ATs; mainly AT-I, II, and III), as one of the primary active components of the traditional Chinese medicine Atractylodes macrocephala, have demonstrated significant antitumorigenic effects against various cancer cells in both in vitro and in vivo studies. This review aims to systematically review the antitumorigenic effects, mechanisms, pharmacokinetics, and safety profile of ATs, aiming to contribute to clinical research and applications. To achieve this, a systematic literature search was conducted across multiple databases, and findings were synthesized narratively to provide a comprehensive overview of the current evidence. This review comprehensively discusses the antitumorigenic effects and mechanisms of ATs, including arresting tumor cell cycle progression, inducing programmed cell death (apoptosis, autophagy, and ferroptosis), inhibiting tumor angiogenesis, suppressing tumor migration and invasion, modulating the tumor immune microenvironment, and enhancing the efficacy of combination therapies. Additionally, their pharmacokinetic properties and safety profile are summarized, with a focus on their research and application prospects. ATs appear to be safe and reliable candidate anticancer agents in preclinical models, exhibiting potent antitumor efficacy both as monotherapy and in combination regimens. Preliminary clinical data from a small pilot study also indicated no signs of toxicity, but more extensive trials are needed to confirm their safety profile in humans. Further studies on their mechanisms are warranted to facilitate their development into clinically effective antitumor agents.

11 January 2026

Designing Antioxidant-Enriched Extracts from Erica carnea L.: Optimization, Kinetics, and Thermodynamic Insights

  • Violeta Jevtovic,
  • Khulood Fahad Saud Alabbosh and
  • Buthainah Ameen Al Shankiti
  • + 8 authors

Erica carnea L. has recently gained attention as a promising natural source of antioxidants suitable for food and beverage applications. This study aimed to obtain an antioxidant-enriched extract by optimizing the key extraction variables. A full factorial design was used to evaluate the effects of ethanol concentration, extraction time, and temperature, followed by validation through multiple antioxidant assays, including DPPH, ABTS, hydroxyl radical scavenging, lipid peroxidation inhibition, and metal chelation. The most efficient extraction was achieved at 30% ethanol, 120 min, and 50 °C, yielding IC50 values of 18.42 μg/mL (LP), 15.04 μg/mL (DPPH), 5.14 μg/mL (MC), 11.28 μg/mL (OH), and 10.06 μg/mL (ABTS), in agreement with the model predictions. Extraction kinetics were described using an unsteady-state diffusion model, supported by low root mean square (RMS) values and high coefficients of determination. Thermodynamic analysis indicated an irreversible, endothermic process, highlighting the energetic requirements for phenolic release from plant tissue. The combined statistical and kinetic approach provides a clearer understanding of how process variables influence antioxidant recovery. In addition to strong antioxidant activity, the optimized extract showed measurable cytotoxic and antibacterial effects. Overall, these findings highlight E. carnea as a valuable material for developing antioxidant-rich formulations, with extraction efficiency governed by predictable kinetic and thermodynamic behavior.

11 January 2026

Over the past decade, research on urolithins has expanded significantly due to their role as mediators between polyphenol-rich diets and human health. Understanding the relationships between ellagitannin intake, gut microbiota composition, and urolithin production is essential for evaluating their biological effects and nutraceutical potential. The primary objective of this review is to critically summarise current knowledge on urolithins, bioactive metabolites derived from ellagitannins in plant-based foods, with a focus on their biosynthesis, bioavailability, protein interactions, and potential therapeutic applications. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify studies on urolithin biosynthesis, absorption, transport mechanisms, protein binding, and incorporation into extracellular vesicles. Relevant articles were critically analysed to synthesise current evidence and highlight emerging concepts. Key findings indicate that after absorption, urolithins bind to serum albumin, which facilitates their transport to target tissues, exerting anti-inflammatory and antioxidant actions. Recent evidence also shows that urolithins can be packaged into extracellular vesicles, suggesting novel mechanisms for intracellular transport and potential therapeutic applications. This review highlights gaps in current knowledge and proposes directions for future research to optimise their therapeutic potential.

11 January 2026

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Molecules - ISSN 1420-3049