Molecules

17 pages, 1856 KiB

Open AccessArticle

Optimizing Ultrasonic-Assisted Extraction Process of Paralepista flaccida: A Comparative Study of Antioxidant, Anticholinesterase, and Antiproliferative Activities via Response Surface Methodology and Artificial Neural Network Modeling

by Mustafa Sevindik, Ayşenur Gürgen, Aras Fahrettin Korkmaz and Ilgaz Akata

Molecules 2025, 30(16), 3317; https://doi.org/10.3390/molecules30163317 (registering DOI) - 8 Aug 2025

Abstract

In this study, extraction conditions were optimized to maximize the biological activities of extracts obtained from Paralepista flaccida, an edible mushroom species. Extraction processes were carried out using an ultrasonically assisted system, and two different optimization approaches were used as follows: Response Surface Methodology (RSM) and Artificial Neural Network–Genetic Algorithm (ANN-GA). The antioxidant potentials of the optimized extracts were evaluated using DPPH, FRAP, TAS, TOS, and OSI parameters; anticholinesterase activities were measured against AChE and BChE enzymes; and antiproliferative activities were investigated in A549, MCF-7, and DU-145 human cancer cell lines. In addition, phenolic contents were determined by LC-MS/MS analysis. The findings revealed that the extracts obtained by the RSM method exhibited a superior biological profile compared to ANN-GA extracts in terms of antioxidant, anticholinesterase, and antiproliferative activities. The high cytotoxicity observed, particularly in the MCF-7 line, supports the anticancer potential of this extract. These results demonstrate that optimization strategies are crucial for increasing not only extract yield but also biological functionality. Full article

(This article belongs to the Special Issue Exploring Bioactive Compounds in Foods and Nutrients for Human Health)

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25 pages, 3010 KiB

Open AccessArticle

The Oncometabolite 2-Hydroxyglutarate Is Upregulated in Post-Prostatectomy PSA Recurrence of Prostate Cancer: A Metabolomic Analysis

by Dontrel W. Spencer Hairston, Shamira Sridharan-Weaver, Abheek Gandhi, Neelu Batra, Blythe P. Durbin-Johnson, Marc A. Dall’Era and Paramita M. Ghosh

Molecules 2025, 30(16), 3316; https://doi.org/10.3390/molecules30163316 (registering DOI) - 8 Aug 2025

Abstract

First-line treatment for localized prostate cancer (PCa) includes radical prostatectomy (RP) for high-risk disease. However, in many cases, patients experience biochemical recurrence (BCR), heralded by rising prostate specific antigen (PSA) levels in the serum. Our goal was to identify metabolic pathways that are disrupted in BCR to determine potential targets of therapy. We conducted metabolomic analysis in prostate tissue from the tumors of 74 patients who underwent prostatectomy as treatment for localized PCa and correlated levels of metabolites with clinical and non-clinical factors. Cholesterol and triglycerides were upregulated in Hispanic vs. non-Hispanic and in obese vs. non-obese individuals, respectively. Both lipids and non-lipids were altered with increasing Gleason grades and clinical stages. High post-RP PSA (>0.1 ng/mL) indicated recurrence (p = 0.0094) and correlated with alterations in 141 metabolites including 114 lipids and 26 non-lipid molecules. The largest increase with high post-RP PSA was in 2-hydroxyglutaric acid (2-HG), a product of the tricarboxylic acid (TCA) cycle, that had previously been established as an oncometabolite in other cancers. 2-HG was highly selective and specific for high post-RP PSA (AUC = 0.8526; p = 0.0002) while Kaplan–Meier curves indicated that among patients who recurred, high 2-HG in the tumor reduced time-to-recurrence from 84 months (for those with low 2-HG) to 38 months (for those with high 2-HG). The addition of D2HG, an enantiomer of 2-HG, increased the growth rate of LNCaP and C4 cells, and also increased Akt and ERK phosphorylation. 2-HG is upregulated in PCa tumors from patients who experience high post-RP PSA indicative of recurrence. Future studies may target this metabolite to prevent recurrent disease. Full article

(This article belongs to the Special Issue Novel Metabolism-Related Biomarkers in Cancer)

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17 pages, 2502 KiB

Open AccessArticle

Influence of Glutinous Rice Raw Material Characteristics on the Aroma Profile of Rice Wine

by Yue Wang, Kangjie Yu, Xiongjun Xiao, Jianxia Tan, Rui Liao, Cong Li, Siyu Li, Nian Liu and Yi Ma

Molecules 2025, 30(16), 3315; https://doi.org/10.3390/molecules30163315 (registering DOI) - 8 Aug 2025

Abstract

Rice wine is a beverage rich in flavor, but the flavor difference caused by rice raw materials has received little attention. To determine the key aroma compounds in rice wine, four types of samples were analyzed by gas chromatography–mass spectrometry (GC–MS), gas chromatography–olfactometry (GC-O), and sensory evaluation. Thirty-eight aroma compounds were detected in the experiment, thirteen of which were identified and quantified using the internal standard method. Additionally, multivariate statistical analyses such as partial least squares discriminant analysis (PLS-DA) effectively revealed three major differential aroma components in rice wine (VIP value ≥ 1). Furthermore, by correlation analysis, it was found that starch and fat in the raw material properties of glutinous rice were significantly and positively correlated with the main differential volatile aroma components in rice wine (p < 0.05). Combined with principal component analysis (PCA), the selection of glutinous rice varieties associated with starch and lipid characteristics during the rice wine brewing process is conducive to improving the overall quality of rice wine. Full article

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38 pages, 3745 KiB

Open AccessReview

Recent Advances in Microtubule Targeting Agents for Cancer Therapy

by Henrique C. Assunção, Patrícia M. A. Silva, Hassan Bousbaa and Honorina Cidade

Molecules 2025, 30(16), 3314; https://doi.org/10.3390/molecules30163314 (registering DOI) - 8 Aug 2025

Abstract

Cancer mortality and the development of cancer resistance present significant challenges that must be addressed to ensure global health. Among anticancer agents, microtubule-targeting agents (MTAs) represent a well-recognized therapeutic approach that disrupts microtubule dynamics, thereby inhibiting cell division, and has been widely used to treat several types of cancers. However, even though MTAs are widely regarded as effective, their potential is limited primarily due to cancer resistance and toxicity. Consequently, in the last years, the exploration of new MTAs with the aim of identifying agents with improved cytotoxicity, selectivity, and adequate pharmacokinetic profile, as well as the ability to evade drug resistance mechanisms, has remained a major concern in the development of anticancer treatment. This review highlights the discovery of new MTAs since 2020, with the goal of understanding the advancements made in this field and its future directions. Special attention is given to structure–activity relationship (SAR) studies that could be important for the discovery of more effective MTAs in the future. Full article

(This article belongs to the Special Issue Nature-Inspired Antitumor Agents, 2nd Edition)

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Molecules, Volume 30, Issue 16 (August-2 2025) – 4 articles

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