Current Drug Metabolism (Volume 27 - Issue 2)

A Lack of Studies on the Metabolism and Disposition of Hot Compound Class: Triphenylphosphonium-Conjugated Compounds

2026-04-13

Exploring Microbiome-Based Therapy: Bacterial Flavonoid Synthesis as a Novel Approach to PCOS Treatment

2026-04-13

Background: PCOS is a common endocrine disorder characterized by metabolic irregularities, hormonal imbalance, and ovarian dysfunction. Traditional therapies, including dietary changes, herbal remedies, and lifestyle modifications, offer limited efficacy in ad-dressing the complex pathophysiology of PCOS.

Method: A literature review was conducted using PubMed, Google Scholar, and ScienceDirect to identify studies on gut microbiota and microbiome-based management strategies for PCOS.

Result: Emerging evidence highlights the role of gut bacteria in regulating hormonal and metabolic functions, sparking interest in microbiota-targeted therapies. Microbial flavonoid synthesis by species such as Streptomyces and Escherichia coli may positively influence en-docrine and metabolic pathways relevant to PCOS.

Discussion: Modulating the gut microbiome, particularly through microbial flavonoid pro-duction, represents a promising therapeutic avenue. However, most evidence remains pre-clinical, with limited clinical validation. Key gaps include mechanistic understanding, safety evaluation, and translational research. Integrating microbiome-targeted interventions with conventional therapies could enhance metabolic and hormonal regulation, offering improved outcomes for women with PCOS.

Conclusion: Microbiome-based medicinal approaches, including microbial flavonoid pro-duction, may offer novel strategies for PCOS management. Rigorous preclinical studies and well-designed clinical trials are essential to establish their efficacy, safety, and therapeutic potential.

Advances in Carbon Nanotubes: Revolutionizing Cancer Diagnosis and Targeted Therapy

2026-04-13

Nanotechnology has been applied to the diagnostic and therapeutic treatment of cancer, with Carbon Nanotubes (CNTs) serving as an effective platform for these processes. In addition to their known physicochemical characteristics, such as high surface area, mechanical strength, and ease of functionalization, CNTs possess pharmacokinetic properties that enable their use in targeted drug-delivery and diagnostic systems. Through functionalization, biodistribution, cellular uptake, and circulatory time can be modulated, thereby overcoming the limitations of traditional therapies, such as low bioavailability and systemic toxicity, and enabling more robust absorption, distribution, metabolism, and excretion profiles. Targeted CNT formulations can reduce off-target exposure and improve therapeutic efficiency through targeted delivery and controlled release. Besides, conjugation of CNTs to imaging or diagnostic agents enables improved assessment of biodistribution and metabolic characteristics, which justify their use as theranostic platforms. This review describes the new developments in CNT-based drug delivery systems for cancer treatment, with particular regard to their interactions with metabolism and the importance of these interactions on drug excretion. The fact that CNTs cross biological barriers and can boost drug bio- availability highlights the importance of these nanoparticles in enhancing the effectiveness of treatment procedures and minimizing toxicity. However, safety issues, including toxicity, long-term safety, and biocompatibility, are also significant impediments to clinical translation. There will be a need to address such issues by systematizing pharmacokinetic and metabolic studies to assist in developing CNT-based solutions for precision oncology.

Zebrafish as a Model Organism to Study Neurotoxicity: A Potential Tool for Neuroprotective Drug Discovery

2026-04-13

Introduction: Danio rerio, the zebrafish, serves as an excellent model in neuroprotective drug discovery due to its conserved nervous system organization, neurotransmitter pathways, antioxidant defenses, and genomic similarity to mammals.

Methods: A systematic literature search following PRISMA 2020 guidelines was conducted across Pub-Med, Scopus, Web of Science, and Google Scholar. Studies published between 2020 and 2025 were prioritized, with earlier key papers included for context. The data on larval, adult, and genetically modified zebrafish models were analyzed for neurotoxic effects, focusing on study design, toxicants, and neurobehavioral or molecular outcomes.

Results: Neurotoxicants such as chlorpyrifos, bisphenol, triphenyl phosphate, aluminum, ammonium acetate, arsenic, zinc, acrylamide, methylmercury, and tris (1,3-dichloro-2-propyl) phosphate were shown to cross the zebrafish blood-brain barrier. These exposures caused significant behavioral alterations, neurotransmitter imbalances, oxidative stress, and gene or protein expression changes related to brain function. Analysis of the transgenic zebrafish revealed notable alterations in neuronal development and axonal morphology upon exposure to various neurotoxic chemicals.

Discussion: Zebrafish display neurotoxic responses with a close resemblance to mammals, supporting their translational value in neurotoxicity and drug discovery studies. However, limitations such as a less complex brain compared to mammals, quick neuronal regeneration, limited tissue access, and difficulties in drug absorption quantification warrant refinements in zebrafish models.

Conclusion: Zebrafish offer a versatile, cost-effective, and genetically tractable system for neurotoxicity and neuroprotection research. This systematic review highlights their crucial role in neuroprotective drug discovery while emphasizing the need for improved methodological approaches to enhance translational reliability.

Computational Chemistry Approach in the Assessment of Potential Acyl Glucuronide-Mediated Toxicity

2026-04-13

Introduction: Acyl glucuronides are common phase II metabolites of xenobiotics and can sometimes contribute to idiosyncratic toxicities. Their reactivity is primarily mediated through acyl migration and/or nucleophilic displacement, and shorter acyl glucuronide half-lives are associated with increased reactivity. This reactivity can lead to metabolite-induced toxicity, posing a significant risk during drug development.

Methods: We developed regression models trained on features derived from Density Functional Theory (DFT) calculations to predict the half-lives of acyl glucuronide metabolites. The aim was to provide a computational tool to guide the design of drug candidates with more stable acyl glucuronide metabolites.

Results: The best-performing model achieved a strong correlation between predicted and experimental half-lives, with an R² of 0.67 on the test set. Predicted half-lives for drugs classified as clinically safe were longer than those for drugs in the warning and withdrawn categories, demonstrating a separation comparable to experimentally measured half-lives.

Discussion: The model is sufficiently accurate to support the optimization of acyl glucuronides for longer half-lives. Further analysis indicated that acyl glucuronide stability can be modulated by electron-donating and electron-withdrawing groups, effects that are effectively captured by the model.

Conclusion: This modeling approach can be applied during drug discovery to reduce the risk of metabolite-related toxicity by enabling in silico screening of compound modifications and ranking them based on predicted effects on acyl glucuronide half-life.