Drugs and Drug Candidates

Background: Malaria remains a significant global health burden, particularly in sub-Saharan Africa, accounting for high rates of illness and death. The growing resistance to frontline antimalarial therapies underscores the urgent need for novel drug targets and therapeutics. Bromodomain-containing proteins, which regulate gene expression through chromatin remodeling, have gained attention as potential targets. Plasmodium falciparum bromodomain protein 1 (PfBDP1), a 55 kDa nuclear protein, plays a key role in recognizing acetylated lysine residues and facilitating transcription during parasite development. Methods: This study investigated ex vivo PfBDP1 gene mutations and identified potential small molecule inhibitors using computational approaches. Malaria-positive blood samples were collected. Genomic DNA was extracted, assessed for quality, and amplified using PfBDP1-specific primers. DNA sequencing and alignment were performed to determine single-nucleotide polymorphism (SNP). Structural modeling used the PfBDP1 crystal structure (PDB ID: 7M97), and active site identification was conducted using CASTp 3.0. Virtual screening and pharmacophore modeling were performed using Pharmit and AutoDock Vina, followed by ADME/toxicity evaluations with SwissADME, OSIRIS, and Discovery Studio. GROMACS was used for 100 ns molecular dynamics simulations. Results: The malaria prevalence rate stood at 12.24%, and the sample size was 165. Sequencing results revealed conserved PfBDP1 gene sequences compared to the 3D7 reference strain. Virtual screening identified nine lead compounds with binding affinities ranging from −9.8 to −10.7 kcal/mol. Of these, CHEMBL2216838 had a binding affinity of −9.9 kcal/mol, with post-screening predictions of favorable drug-likeness (8.60), a high drug score (0.78), superior pharmacokinetics, and a low toxicity profile compared to chloroquine. Molecular dynamics simulations confirmed its stable interaction within the PfBDP1 active site. Conclusions: Overall, this study makes a significant contribution to the ongoing search for novel antimalarial drug targets by providing both molecular and computational evidence for PfBDP1 as a promising therapeutic target. The prediction of CHEMBL2216838 as a lead compound with favorable binding affinity, drug-likeness, and safety profile, surpassing those of existing drugs like chloroquine, sets the stage for preclinical validation and further structure-based drug design efforts. These findings are supported by prior experimental evidence showing significant parasite inhibition and gene suppression capability of predicted hits. Full article

The methods utilized in the drug discovery pipeline routinely combine machine learning and deep learning algorithms to enhance the outputs. The generation of a drug target, through virtual screening and computational analysis of databases used for target discovery, has increased the reliability of the machine learning and deep learning incorporated techniques. Recent technological advances in human immunology have provided improved tools that allow a better understanding of the biological and molecular mechanisms leading to the protective human immune response to pathogens, inspiring new strategies for vaccine design. Immunoinformatics approaches are more beneficial, and thus there is a demand for modern technologies such as reverse vaccinology, structural vaccinology, and system approaches in developing potential vaccine candidates. System theory, defined as a set of machine learning, control theory, and optimization-based methods applied to networked systems, provides a unifying framework for modeling and analyzing biological complexity. In this review, we explore the application of such computational methods at every stage of the therapeutic pipeline, including lead discovery, optimization, and dosing, as well as vaccine target prediction and immunogen design. Here, we summarize the system theoretic methods which provide insights into developed approaches and their applications in rational drug discovery and vaccine formulations. The approaches ranged in the review yield accurate predictions and insights. This review is intended to serve as a resource for researchers seeking to understand, adopt, or build upon system theoretic techniques in drug and vaccine development, offering both conceptual foundations and practical directions. Full article

Background/Objectives: Since the emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of compounds with antiviral potential from medicinal plants has been extensively researched. This study aimed to investigate plant metabolites with in vitro inhibitory potential against SARS-CoV-2 targets, including 3CL_pro, PL_pro, Spike protein, and RdRp. Methods: A systematic review was conducted following PRISMA guidelines, with literature searches performed in six electronic databases (Scielo, ScienceDirect, Scopus, Springer, Web of Science, and PubMed) from January 2020 to February 2024. Computational analyses using SwissADME, pkCSM, ADMETlab, ProTox3, Toxtree, and DataWarrior were performed to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles as well as other medicinal chemistry parameters of these compounds. Results: A total of 330 plant-derived compounds with inhibitory activities against the proposed targets were identified, with compounds showing IC₅₀ values as low as 0.01 μM. Our findings suggest that several plant metabolites exhibit significant in vitro inhibition of SARS-CoV-2 targets; however, few molecules exhibit drug development viability without further adjustments. Additionally, after these evaluations, two phenolic acids, salvianic acid A and protocatechuic acid methyl ester, stood out for their potential as candidates for developing antiviral therapies, with IC₅₀ values of 2.15 μM against 3CL_pro and 3.76 μM against PL_pro; respectively; and satisfactory in silico drug-likeness and ADMET profiles. Conclusions: These results reinforce the importance of plant metabolites as potential targets for antiviral drug discovery. Full article

Background: One of the challenges of applying artificial intelligence (AI) methods to drug discovery is the difficulty of laboratory synthesizability for many AI-discovered molecules. Often, in silico techniques and metrics such as the computationally enabled synthesizability score and AI-based retrosynthesis analysis are used. Methods: In this paper, we present a predictive synthesizability method that integrates the gains of synthetic accessibility scoring and the benefits of AI-driven retrosynthesis analysis tools to evaluate the synthesizability of AI-generated lead drug molecules. Results: We explored the proposed method by using it to analyze the synthesizability of a set of 123 novel molecules generated using AI models. The analysis of the synthesis route of the four best molecules from the set in terms of synthesizability, as identified using the proposed method, is presented. Conclusions: This strategy enables quick initial screening and more comprehensive actionable synthetic pathways, thereby balancing speed and detail, and favoring simple routes to avoid the risk of pursuing non-synthesizable compounds in the drug development pipeline. Full article

Background: TMPRSS2 plays an important role in the viral entry mechanisms of influenza viruses and coronaviruses. Therefore, TMPRSS2 seems to be a suitable antiviral drug target. To exclude possible side effects of TMPRSS2 truncation in an early stage of drug in-vitro testing, this study aims to analyze the impact of TMPRSS2 truncation via antisense peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) targeting immune cells, using the example of regulatory T cells (Treg). Methods: TMPRSS2 was truncated in human Tregs using a splice-modulating PPMO. Effects on Treg function were analyzed by evaluation of surface marker and transcription factor expression, cytokine secretion, and effector cell suppression capability. Results: PPMO treatment led to a slight concentration-dependent toxicity in Tregs. Tregs with truncated TMPRSS2 behave similarly to untreated and control PPMO-treated cells in the analyzed assays. Conclusions: Treg function is not altered after TMPRSS2 truncation and therefore, no unwanted side effects in regard of Tregs are expected when using TMPRSS2-truncating PPMO as an anti-viral drug. Full article

Cytochrome P450 (CYP450) enzymes are pivotal in the metabolism of numerous anticancer agents, with CYP3A4 being the predominant isoform involved. Inhibition of CYP450 enzymes is a major mechanism underlying clinically significant drug-drug interactions (DDIs), particularly in oncology, where polypharmacy is frequent. This review aims to provide a comprehensive and critical overview of CYP450 enzyme inhibition, focusing specifically on the impact of kinase inhibitors (KIs) and poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. A systematic review of the current literature was conducted, focusing on the molecular mechanisms of CYP450 inhibition, including reversible, time-dependent, mechanism-based, and pseudo-irreversible inhibition. Specific attention was given to the inhibitory profiles of clinically relevant KIs and PARP inhibitors, with analysis of pharmacokinetic consequences and regulatory considerations. Many KIs, such as abemaciclib and ibrutinib, demonstrate time-dependent or quasi-irreversible inhibition of CYP3A4, while PARP inhibitors like olaparib and rucaparib exhibit moderate reversible and time-dependent CYP3A4 inhibition. These inhibitory activities can significantly alter the pharmacokinetics of co-administered drugs, leading to increased risk of toxicity or therapeutic failure. Regulatory guidelines now recommend early identification of time-dependent and mechanism-based inhibition using physiologically based pharmacokinetic) (PBPK) modeling. CYP450 inhibition by KIs and PARP inhibitors represents a critical but often underappreciated challenge in oncology pharmacotherapy. Understanding the mechanistic basis of these interactions is essential for optimizing treatment regimens, improving patient safety, and supporting personalized oncology care. Greater clinical vigilance and the integration of predictive modeling tools are necessary to mitigate the risks associated with CYP-mediated DDIs. Full article

Breast cancer continues to represent one of the most widespread and lethal health afflictions on a global scale. The advancement of this malignancy is predominantly influenced by genetic mutations that precipitate unregulated cellular growth and proliferation, with oxidative stress being a crucial factor in all phases of carcinogenic development. Oxidative stress emerges from a disruption in the equilibrium between reactive oxygen species (ROS) and antioxidants, which inflicts damage on cellular components and facilitates the onset of cancer. Although numerous studies have advocated the notion that augmenting antioxidant levels may confer protection against cancer, other investigations have yielded contradictory results. Nevertheless, the effectiveness of antioxidants in cancer prophylaxis remains contentious, with research exhibiting variable outcomes. Certain studies have indicated that a high consumption of fruits and vegetables abundant in antioxidants may lower cancer risk. However, the irrefutable evidence is currently absent. Furthermore, the chemotherapeutic agents, such as taxanes and cisplatin, utilized in breast cancer management are reported to produce ROS as an integral aspect of their therapeutic mechanisms, thereby highlighting the intricate interplay between redox equilibrium and oncological treatment. This review emphasizes the pro-oxidant hypothesis, which asserts that heightened levels of ROS may selectively annihilate cancer cells, given that normal cells generally sustain low levels of ROS. Some recent reports have indicated that the application of plant-based molecules as a therapeutic supplement may help treat breast cancer effectively. However, a comprehensive understanding of the role of oxidative stress in breast cancer and use of antioxidants could pave the way for more precisely targeted therapeutic strategies aimed at the modulation of redox homeostasis. Full article

Current treatment options for Alzheimer’s disease target neurotransmitters following the disease onset, and they offer limited efficacy without slowing down the disease progression. There has been an increasing concern in recent years targeting the histamine H3 receptor (H3R) in treating cognitive disorders, including dementia. Preclinical studies have shown that antagonists of H3R or inverse agonists enhance the cognitive function in animal models with dementia by increasing the release of neurotransmitters associated with learning and memory. This review employed a systematic literature search across databases including PubMed, Scopus, Google Scholar, and ClinicalTrials.gov, selecting peer-reviewed studies. The results of this study illustrate the complex landscape of research on H3R modulators in dementia, highlighting both promising findings and ongoing challenges in translating preclinical discoveries into effective clinical interventions. Knowing the role of H3R in dementia and developing novel pharmacological interventions targeting these receptors represent a promising avenue for future research, leading to the development of new treatments for this devastating condition. Full article

Background/Objectives: Pancreatic cancer is the seventh most lethal type of cancer in the world, and its treatment, which is largely inefficient, is based on surgery and/or non-specific chemotherapy. Its malignant features are characterized by complex cell signaling pathways, which can be used as targets for new drugs. Methods: In this study, glucal-based compounds were synthetized, with substitution based on fluorine, nitrogen and aromatic ring addition. The compounds were tested in the pancreatic cell culture Mia-PaCa-2 and cell viability was assessed, with further IC50 calculation, stability and selectivity. Molecular docking was performed to evaluate the probable molecular target for 5b and in silico physicochemical properties were determined. Results: One molecule, named 5b, with two fluorine atoms inserted in the aromatic ring, exerted potent inhibitory activity on cell growth (IC50 = 1.39 µM), which was selective for pancreatic cells. Through molecular docking studies, the compound was found to be positioned in the active site of JAK3, indicating inhibition of such protein, which has a role in tumoral cell growth. Moreover, 5b was stable for 24 months and had physicochemical properties to permeate cell membranes, good oral absorption, and low potential to cause toxicity. Conclusions: These data suggest that 5b can be druggable and can be considered as a prototype for a new course of treatment in pancreatic cancer. Full article

Background/Objectives: The thiazolo [5,4-d]pyrimidine scaffold is a class of drugs known for its anticancer, antitumor, anti-inflammatory, and antimicrobial properties. In this study, the electrochemical properties of novel thiazolo [5,4-d]pyrimidine derivatives and their interactions with DNA were characterized for the first time using voltammetric methods. Determining the interactions of new drug candidate molecules with DNA is crucial for drug development studies and is the main objective of this research. Methods: Both molecules were immobilized on the surface of the electrodes by passive adsorption, and their electrochemical properties were determined by voltammetric methods through reduction currents. Their interactions with DNA were carried out in the solution phase and examined by the changes in the oxidation peak potential and current of the guanine base. Results: For both molecules, it was determined that the electrochemical reduction processes are diffusion-controlled and irreversible, with an equal number of protons and electrons being transferred during this process. The detection limits for TP-NB (4-chloro-N-(5-chlorothiazolo [5,4-d]pyrimidin-2-yl)-3-nitrobenzamide) and TP-PC (1-(2-(4-(4-carbamoylpiperidin-1-yl)-3-nitrobenzamido)thiazolo [5,4-d]pyrimidin-5-yl)piperidine-4-carboxamide) were determined to be 12 µg/mL and 16 µg/mL, respectively. As a result of the interaction between both molecules with DNA, the guanine oxidation current decreased. It was found that TP-NB could act as an intercalator, while TP-PC could affect DNA electrostatically, both showing toxic effects on DNA. Conclusions: An electrochemical method was developed for the rapid, cost-effective, and sensitive detection of both molecules and their DNA interactions. Both compounds exhibited notable affinity towards DNA, as evidenced by significant changes in oxidation peak currents, shifts in peak potentials, and calculated toxicity values. These findings suggest their potential use as DNA-interacting drugs, such as anticancer and antimicrobial agents. Our study offers a quick, cost-effective, and reliable electrochemical approach for the evaluation of drug–DNA interactions. Full article

Engineered exosomes have emerged as transformative drug carriers, uniquely equipped to overcome biological barriers in central nervous system (CNS) disorders and cancer therapy. These natural extracellular vesicles, derived from cell membranes, offer inherent biocompatibility, low immunogenicity, and the ability to traverse physiological obstacles such as the blood–brain barrier (BBB) and dense tumor stroma. Recent advances in exosome engineering—including surface modification (e.g., ligand conjugation for receptor-mediated targeting) and cargo loading (siRNA, CRISPR-Cas systems, and chemotherapeutics)—have enhanced their precision and therapeutic utility. For CNS delivery, exosomes functionalized with brain-homing peptides (e.g., RVG or TfR ligands) have enabled the efficient transport of neuroprotective agents or gene-editing tools to treat Alzheimer’s disease or glioblastoma. In oncology, engineered exosomes loaded with tumor-suppressive miRNAs or immune checkpoint inhibitors exploit tumor microenvironment (TME) features, such as acidity or enzyme overexpression, for spatially controlled drug release. Furthermore, hybrid exosome–liposome systems and exosome–biomaterial composites are being explored to improve payload capacity and stability. Despite progress, challenges persist in scalable production, batch consistency, and regulatory standardization. This review critically evaluates engineering strategies, preclinical success, and translational hurdles while proposing innovations such as AI-driven exosome design and patient-derived exosome platforms for personalized therapy. By bridging nanotechnology and biomedicine, engineered exosomes can represent a paradigm shift in targeted drug delivery, offering safer and more effective solutions for historically intractable diseases. Full article

Background/Objectives: Bacterial infections remain among the top ten major public health concerns, contributing to a high number of incidences of disease and mortality worldwide, exacerbated by the rise of multidrug-resistant bacteria (MDRB). Consequently, it is crucial to develop novel antimicrobial strategies, including the use of functional nanoparticles. Gold nanoparticles (GNPs) have emerged as promising candidates due to their unique optical properties, particularly their ability to efficiently convert absorbed light into heat through the photothermal (PT) effect, which can be harnessed for bacteria eradication. Methods: Chitosan was modified with 3-mercaptopropionic acid to introduce sulfur groups, facilitating gold deposition onto chitosan nanoparticle (TCNPs) surface. The gold shell was subsequently formed via a seed-mediated method, wherein gold seeds were adsorbed onto TCNPs and further grown to form the shell. Photothermal effect on the bacterial viability was evaluated. Results: TCNPs with a size of 178 nm and spherical morphology were obtained. After the gold shell (TCNP@Au) exhibited a photothermal conversion efficiency of 31%, making them a promising photothermal agent for bacterial clearance. Notably, the viability of Escherichia coli was significantly reduced in the presence of TCNP@Au and was almost eradicated upon PT treatment. In contrast, TCNP@Aus were non-toxic for Staphylococcus aureus. Conclusions: TCNP@Au demonstrated favorable photothermal properties, presenting a novel nanoplatform for antibacterial applications, particularly against Gram-negative bacteria. However, further investigation is required to optimize the PT-based strategies against Gram-positive bacteria, such as S. aureus. Full article

Background: Metritis, a common postpartum uterine infection in bovines, poses substantial challenges in livestock management, including compromised fertility and economic losses. Poor uterine drug penetration and systemic side effects, necessitating innovative localised delivery systems and limiting current systemic antibiotic treatments. Aim: This study aimed to develop and evaluate the potential effect of the ofloxacin-loaded hydrogel as a localised drug delivery system to treat metritis in bovine. The focus was on achieving sustained drug release, enhanced antibacterial efficacy and reduced inflammation in the endometrium. Materials and Methods: The CS/PVA hydrogel was synthesised using a freeze–thaw method and further optimised for drug encapsulation efficiency (96.7 ± 2.1%), stability and biocompatibility. Physicochemical characterisation included swelling behaviour, mechanical properties and rheological analysis. In vitro drug release profiles in the simulated uterine fluid were assessed over 72 h and antibacterial activity was tested against common uterine pathogens such as Escherichia coli and S. aureus. In vivo studies were conducted on bovines diagnosed with endometritis to evaluate clinical recovery. Results: The SEM image of the ofloxacin-loaded CS/PVA hydrogel resulted in a smooth and porous structure demonstrating larger pore size than the blank. The rheological study suggested higher stability and elastic behaviour. Antibacterial assays on E. coli and S. aureus revealed significant inhibition zones, respectively, indicating potent efficacy. In vivo, evaluated on treated bovine, reduced bacterial loads were exhibited (2.86 × 10^5A CFU/mL → 6.37 × 10^2B CFU/mL), clinical improvement was marked and uterine inflammation was resolved. Conclusions: Ofloxacin-loaded hydrogels represent a promising localised treatment for bovine metritis, offering sustained antibacterial action and improved clinical outcomes. This approach addresses the limitations of systemic antibiotic therapies and provides a practical solution for enhanced veterinary care. Further studies are recommended to validate these findings in more extensive field trials and explore commercialisation potential. Full article

Background: The cholinergic hypothesis is an elementary approach employed for the research and drug discovery of novel anti-Alzheimer therapeutics. Method: In this context, the study focuses on synthesizing and evaluating a new series of chalcone derivatives (3a–3j) as multifunctional therapeutic agents, specifically investigating their antioxidant potential using the DPPH method with ascorbic acid as a standard. Ellman’s protocol for acetylcholinesterase inhibition assay was performed using donepezil as a standard, and computational insights were explored through molecular docking and ADME profiling. Results: Compounds 3a, 3d, 3e, 3f, and 3h exhibited excellent antioxidant activity compared to the standard. Most of the compounds exhibited moderate to good (3b, 3c, and 3h) AChE inhibitory activity. Molecular docking studies revealed conventional hydrogen bonding and π-π interactions with the enzyme’s active residues, facilitated by their electronegative groups and phenyl rings, respectively. In addition, a pharmacokinetic study was conducted using computational approach to assess druggability. The results demonstrated that compound 3b is an outstanding lead candidate with appreciable AChE inhibitory activity. Conclusions: The combined experimental and computational results of this study highlight the multifunctional nature of chalcone derivatives, suggesting their potential as promising therapeutic agents for the discovery of novel AChE inhibitors that could be employed in the management of Alzheimer’s disease and oxidative stress-related diseases. Full article

To date, numerous studies have emerged that indicate the possible role of epigenetic modulation in the development and progression of several diseases, including cancer. Epigenetic alterations participate in various steps of carcinogenesis. They play important regulatory roles in processes like cell division, proliferation, angiogenesis, and metastasis. Thus, epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNAs serve as attractive and promising targets for cancer prevention and anti-cancer therapy. Epigenetic drugs or epi-drugs possess the ability to reverse many such epigenetic alterations and thus can help manage the clinical manifestations of cancer. Epigenetic drugs broadly target epigenetic modifications, including DNA methylation and histone post-translational modifications, to manifest their effects. Several naturally occurring as well as chemically synthesized compounds have been recognized as epigenetic drugs. Some of them are clinically approved, while many are in their preclinical and clinical trials. In this review, we aim to present a broad overview of the epigenetic modifications implicated in carcinogenesis. The review also compiles various epigenetic drugs that are approved for clinical practice, as well as those that are in the preclinical and clinical stages of investigation for anti-cancer therapy. Full article

Background/Objectives: Uveal melanoma (UM) is a rare but deadly ocular cancer. This review summarizes the characteristics of uveal melanoma and current therapeutic options for primary uveal melanoma and metastatic uveal melanoma, and introduces recent development of therapeutic strategies in preclinical animal studies and clinical trials. Methods: The literature search was conducted to identify relevant articles for UM studies. It was performed using PubMed for articles in English until March 2025. Information on clinical trials was also obtained from ClinicalTrial.gov. Results: Uveal melanoma originates from melanocytes, similar to skin melanoma. However, uveal melanoma has different mutations from skin melanoma. Thus, chemotherapy and immunotherapy, which are effective for skin melanoma, are ineffective for uveal melanoma. Current therapies for UM include radiation therapy, surgical resection, liver-directed therapies, and recently FDA-approved tebentafusp. Although a wide variety of available and newly developed therapies have been tested in clinical trials for UM, tebentafusp is the only FDA-approved therapy for metastatic UM. Given the excessive expression of vascular endothelial growth factor (VEGF) in UM patients with metastatic diseases, anti-VEGF strategies are being tested in clinical trials and pre-clinical animal models. Conclusions: This review summarizes an overview of current therapies and the development of therapeutic strategies in clinical trials and pre-clinical animal models. Despite successful control of primary tumors, 50% of UM patients still experience metastasis in the liver. Although tebentafusp improves the overall survival (OS) of a certain population of UM patients, robust strategies for preventing UM metastasis represent a critical unmet need. Further investigations of the heterogeneity of UM cells and mechanisms of UM metastasis are needed in the future. Full article

The COVID-19 pandemic, driven by the high transmissibility and immune evasion caused by SARS-CoV-2 and its variants (e.g., Alpha, Delta, Omicron), has led to massive casualties worldwide. As of November 2024, the International Committee on Taxonomy of Viruses (ICTV) has identified 14,690 viral species across 3522 genera. The increasing infectious and resistance to FDA and EMA-approved antivirals, such as 300-fold efficacy reduction in Nirmatrelvir against the SARS-CoV-2 3CLpro, highlight the need for mutation-stable antivirals, likewise targeting the essential host proteins like kinases, heat shock proteins, lipid metabolism proteins, immunological pathway proteins, etc. Unlike direct-acting antivirals, HDAs reduce the risk of resistance by targeting conserved host proteins essential for viral replication. The proposal for repurposing current FDA-approved drugs for host-directed antiviral (HDA) approach is not new, such as the Ouabain, a sodium-potassium ATPase inhibitor for herpes simplex virus (HSV) and Verapamil, a calcium channel blocker for influenza A virus (IAV), to name a few. Given the colossal potential of the mutation-stable HDA approach to exterminate the virus infection, it has been increasingly studied on SARS-CoV-2. This review aims to unravel the interaction between viruses and human hosts and their successfully proposed host-directed antiviral approach to provide insight into an alternative treatment to the rampant mutation in SARS-CoV-2. The benefits, limitations, and potential of host protein-targeted antiviral therapies and their prospects are also covered in this review. Full article

The mini-review highlights the innovative development of hetero-dinuclear metallic complexes, with a specific focus on zinc(II) metal centers arranged in a square-pyramidal configuration. The work presented, stemming from our research group in collaboration with others between the years 2020 and 2024, makes significant contributions to this area, emphasizing their potential applications in bioinorganic chemistry, particularly in the context of drug discovery. These advances not only expand the fundamental understanding of such complexes but also lay the groundwork for the design of novel hetero-dinuclear metallic compounds with therapeutic potential. The interaction of these complexes with biological systems and their implications for drug development are critical for future research in bioinorganic chemistry, offering new pathways for targeted treatments and molecular therapies. Full article

Background/Objectives: Sleep is essential to human health, playing a vital role in physical and mental well-being. Sleep disorders can lead to significant health complications, such as cardiovascular problems, diabetes, obesity, and depression. In Brazil, plants such as passionflower (Passiflora spp.), chamomile (Matricaria chamomilla L.) and mulungu (Erythrina spp.) are widely used in folk medicine for their sleep-promoting properties. This article reviews the existing literature on the sleep-promoting effects of these plants, focusing on the Brazilian context and popular knowledge of their use. Methods: An integrative literature review was conducted, including scientific articles in English and Portuguese from PubMed, Scielo and Google Scholar databases. Ethnobotanical studies documenting the traditional use of these plants in Brazil and clinical and preclinical research on their sleep-promoting effects were included. Results: The juice and infusion of the leaves and fruits of passionflower are mainly used to treat anxiety and insomnia, chamomile flower tea is used for its sedative effects, and mulungu bark decoctions are used for their sedative and anxiolytic properties. These popular uses are supported by scientific studies demonstrating the efficacy of these plants in treating insomnia, anxiety, and stress. Conclusions: The recognition of traditional knowledge and the inclusion of these plants in RENISUS highlights their importance for public health in Brazil. However, more rigorous clinical trials are needed to confirm their efficacy and safety and ensure their safe integration into modern medicine. Full article