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.

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.

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.

Tanacetum balsamita is a perennial medicinal plant belonging to the Asteraceae family. The species bears a long history as a valuable traditional drug in different cultures, while it is an essential component in the traditional cuisine of several countries. In this context, our literature review aims at providing a comprehensive overview of T. balsamita, covering its traditional uses, phytochemistry, biological activities, and toxicity from 1983 to 2024. Methods: Various databases were used to collect the information, including Scopus, Science Direct, Google Scholar, PubMed, and Web of Science. Results and conclusions: Although many of its traditional uses have gradually faded into obscurity over the centuries, recent decades have rekindled the interest in this species. Recent ethnobotanical surveys have reported the use of this species against various health-related conditions, while current pharmacological studies have corroborated several health benefits of the species, such as antioxidant, antidiabetic, anti-hyperpigmentation, anticancer, and antimicrobial activities. The validated properties are mainly attributed to the presence of multiple phytoconstituents belonging to flavonoids, phenolic acids, terpenes, and fatty acids, which could also indicate potential uses for T. balsamita in the food industry as a natural preservative and flavoring agent of food products.

Background/Objectives: The integration of Artificial Intelligence (AI) and Machine Learning (ML) in pharmaceutical research and development is transforming the industry by improving efficiency and effectiveness across drug discovery, development, and healthcare delivery. This review explores the diverse applications of AI and ML, emphasizing their role in predictive modeling, drug repurposing, lead optimization, and clinical trials. Additionally, the review highlights AI’s contributions to regulatory compliance, pharmacovigilance, and personalized medicine while addressing ethical and regulatory considerations. Methods: A comprehensive literature review was conducted to assess the impact of AI and ML in various pharmaceutical domains. Research articles, case studies, and industry reports were analyzed to examine AI-driven advancements in predictive modeling, computational chemistry, clinical trials, drug safety, and supply chain management. Results: AI and ML have demonstrated significant advancements in pharmaceutical research, including improved target identification, accelerated drug discovery through generative models, and enhanced structure-based drug design via molecular docking and QSAR modeling. In clinical trials, AI streamlines patient recruitment, predicts trial outcomes, and enables real-time monitoring. AI-driven predictive maintenance, process optimization, and inventory management have enhanced efficiency in pharmaceutical manufacturing and supply chains. Furthermore, AI has revolutionized personalized medicine by enabling precise treatment strategies through genomic data analysis, biomarker discovery, and AI-driven diagnostics. Conclusions: AI and ML are reshaping pharmaceutical research, offering innovative solutions across drug discovery, regulatory compliance, and patient care. The integration of AI enhances treatment outcomes and operational efficiencies while raising ethical and regulatory challenges that require transparent, accountable applications. Future advancements in AI will rely on collaborative efforts to ensure its responsible implementation, ultimately driving the continued transformation of the pharmaceutical sector.

Background/Objectives: This systematic review explores the utilization of electrospinning for the incorporation of natural compounds, focusing on their pharmacological applications. Methods: This systematic review focused on studies investigating the incorporation of natural bioactive compounds into nanofibers produced via the electrospinning technique for pharmacological applications. The search was conducted for English-language articles published online between 1 January 2013 and 10 December 2023. The review followed a structured approach, excluding review articles, clinical studies, and gray literature such as unpublished works, non-peer-reviewed journals, theses, and industry data. Results: The review of 99 articles highlighted the advantages of electrospun nanofibers in tissue regeneration, infection control, and controlled drug release, with notable potential in oncology for targeted antitumor drug delivery. It discussed the influence of polymers and solvents on fiber characteristics and identified a significant gap in cosmetic applications, emphasizing the technique’s potential for prolonged release and improved ingredient stability. Additionally, this review noted the underutilization of marine-derived substances, which possess rich bioactive properties that could benefit biomedical and cosmetic fields. Conclusions: This systematic review highlights the advantages of electrospinning for pharmacological applications, including tissue regeneration, infection control, and controlled drug release, with promising potential in oncology. However, gaps were identified in the cosmetic field and the use of marine-derived substances. Future advancements in electrospinning technology and interdisciplinary collaboration are essential to unlocking its full potential in medicine and cosmetics.

Nicotinamide adenine dinucleotide (NAD+) is one of the most essential coenzymes that is widely distributed in human tissues. However, with the progress of aging, the NAD+ level gradually decreases, thus impacting the metabolic dynamics and heightening susceptibility to various pathologies. Increasing NAD+ levels are expected to delay aging and improve age-related degenerative diseases. Amino–carboxylic semialdehyde dehydrogenase (ACMSD) is a key enzyme involved in the de novo synthesis of NAD+. It reduces the intermediate products of the de novo synthesis pathway by catalyzing the degradation of α-amino-β-carboxyethylglutamic acid-ε-semialdehyde (ACMS), thus reducing the production of NAD+. Genetic and pharmacological inhibition of ACMSD has been demonstrated to increase NAD+ levels in vitro and in vivo, thus making it a potential target for the treatment of NAD+-deficient diseases. In this mini-review, we detail the molecular mechanisms regulated by ACMSD. We also discuss the potential efficacy and progress of ACMSD inhibitors in treating aging and age-related diseases.

Background/Objectives: The marine sponge Plakortis halichondrioides is notable for its capacity to accumulate a large array of secondary metabolites. The present research aims at discovering new secondary metabolites from P. halichondrioides with potential applications in medicine. Methods: Plakortilactone (1) and seco-plakortide F acid (2), two new polyketides, along with known manadodioxan D (3), 13-oxo-plakortide F (4), plakortide F (5), and manadodioxan E (6), were isolated from P. halichondrioides. We achieved the structural elucidation of 1 and 2 using modern spectroscopic methods. The relative stereochemistry of 1 was proposed on the basis of 1D- and 2D-NMR data in combination with molecular modeling studies. Additionally, the absolute configuration of 2 was established through chemical correlation to 5. We screened some of the isolated compounds against the malaria parasite Plasmodium falciparum 3D7 non-resistant (wild-type resistant) strain, the tuberculosis bacterium Mycobacterium tuberculosis, the prostate cancer cell line DU-145, and the melanoma cell line A-2058. Results: minimal activity was detected for 2 against these cancer cells. In contrast, 3 and 4 displayed activity against DU-145 cells with IC50 values of 1.6 µg/mL and 4.5 µg/mL, respectively, and A-2058 cells with IC50s of 2.6 µg/mL and 7.7 µg/mL, respectively. In the antiplasmodial activity assay 3 appeared more active (IC50 = 1.7 µg/mL) than 4 (IC50 = 3.1 µg/mL). Meanwhile, 2 displayed only moderate activity (IC50 = 39.3 µg/mL). In the antimycobacterial activity assay 2 exhibited moderate inhibition (MIC = 75.1 µg/mL). In contrast, a 1:1 mixture of 3 and 4 demonstrated higher activity (MIC = 26.3 µg/mL). Conclusions: the biological activity data together with ADMET predictions indicated favorable pharmacokinetic properties for 3.

COVID-19, first identified in December 2019 in Wuhan, China, is caused by the SARS-CoV-2 virus, a pathogen that primarily targets the respiratory system and can lead to severe conditions such as acute respiratory distress syndrome (ARDS). Among the seven coronaviruses known to infect humans, three—SARS-CoV, MERS-CoV, and SARS-CoV-2—are associated with severe illness and significant morbidity. SARS-CoV-2 is an enveloped, single-stranded RNA virus that utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry. The genetic sequence of SARS-CoV-2 is highly mutable, leading to the emergence of variants that alter disease pathology and transmission dynamics. The World Health Organization (WHO) has classified these mutations into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring (VUMs). This review provides an in-depth analysis of both historical and emerging SARS-CoV-2 variants, summarizes recent advancements in diagnostic methods for SARS-CoV-2 detection, and discusses current therapeutic strategies for COVID-19, with a particular focus on virus-like particle (VLP) vaccines developed in recent years. Additionally, we highlight ongoing therapeutic approaches and their implications for managing COVID-19.

Background/Objectives: The interaction of bioactive compounds derived from plants with drugs has become a significant area of investigation due to its potential to improve, reduce, or have no effect on therapeutic outcomes. Due to the dual effect of these interactions, elucidating the underlying mechanisms is essential for establishing a therapeutic strategy. This study emphasizes the significant findings, mechanisms, and clinical implications of drug–plant bioactive interactions. It calls for more studies to seek safe and effective incorporation into clinical practice. Methods: To identify relevant studies, we performed a systematic literature search based on various scientific databases from 11 August 2024 to 30 December 2024. The search will be based on relevant keywords such as synergy, antagonism, plant bioactive compounds, and drug interactions supplemented with secondary terms such as phytochemicals, herb-drug interactions, pharmacokinetics, and pharmacodynamics. Results: Plant bioactives, including polyphenols, flavonoids, alkaloids, and terpenoids, display valuable biological activities that can interact with medications in three principal ways: synergy, additive effects, and antagonism. Synergy occurs when the combined effects of plant chemicals and pharmaceuticals outweigh the sum of their separate effects, increasing therapeutic effectiveness or allowing dosage decrease to reduce adverse effects. Additive effects occur when the combined impact equals the total individual effects, resulting in better outcomes without increasing risk. Antagonism occurs when a plant ingredient reduces or counteracts the effects of a medicine, thereby jeopardizing treatment. In addition, specific interactions may have no discernible effect. The chemical makeup of bioactive chemicals, medication pharmacokinetics, and individual patient characteristics such as genetics and metabolism all impact the intricacy of these interactions. Conclusions: Pharmacokinetics and pharmacodynamics of drugs can be considerably modulated through their interactions with plant bioactive components, which may cause a significant decrease in efficacy or increase in toxicity of therapeutic agents. More studies are needed to clarify mechanisms of action, prove clinical relevance, and create guidelines for safe co-administration. This integrative approach can mitigate those risks and allow for therapeutic optimization by introducing pharmacogenomics and personalized medicine approaches.

Background/Objectives: Cancer is a leading cause of death. However, recently developed immunotherapies have shown significant promise to improve cancer treatment outcomes and survival rates. Pembrolizumab, a cancer immunotherapy drug, enables a strong T-cell response specifically targeting cancer cells to improve patient outcomes in more than 16 types of cancer. The increasing demand for pembrolizumab, the highest selling drug in 2023, increases global dependence on drug production, which can be vulnerable to supply chain disruptions. Methods: Cell-free protein synthesis (CFPS) is a rapid in vitro protein production method that could provide the production of an immunotherapy drug in an emergency and could facilitate on-demand production of the therapeutic at the point of care if needed. Furthermore, CFPS has potential as a production platform of biosimilars, as the patent for pembrolizumab is set to expire in 2028. Results: This work presents the design, synthesis, and target-binding affinity of a novel single-chain variable fragment of pembrolizumab (Pem-scFv) using CFPS. The CFPS production of Pem-scFv also enables the direct optimization of synthesis reaction composition and expression conditions. The conditions of 30 °C, 35% (v/v) cell extract, and an oxidizing redox environment resulted in the highest Pem-scFv soluble yield of 442 µg/mL. An affinity assay demonstrated significant binding between the CFPS-produced Pem-scFv and the PD-1 target. Computational simulations of Pem-scFv folding and binding corroborate the experimental results.

The Group for the Promotion of Pharmaceutical Chemistry in Academia (GP2A) held its 32nd annual conference in August 2024 at the University of Coimbra, Portugal. There were 8 keynote presentations, 12 early career researcher oral presentations, and 34 poster presentations. Four awards were delivered, two for the best oral communications and two for the best poster presentations.

Rising levels of antibiotic-resistant bacteria have led to increasing interest in the use of phage therapy as an alternative treatment. While phage therapy is conceptually simple, and numerous semi-anecdotal data suggest that it could be effective if properly managed, there have been only a few randomized, double-blind clinical trials of phage therapy so far. These trials unequivocally showed that phage therapy is safe, but there is still a paucity of data on its efficacy for managing various bacterial infections. One common response to this situation is that there is a mismatch between the regulations that govern the testing of new drugs, that is, chemical agents, and biological agents like bacteriophages. Another response has been to sidestep clinical trial testing and to use phages to treat infected patients on an individual basis, sometimes called the magistral phage approach. In this paper, we argue that regulations are not the true barrier to approval of phage therapy as drugs but rather it is the lack of efficacy data. There is no one reason behind the failures of recent clinical trials. Instead, these demonstrate the complexity of implementing a therapy where both the treatment and disease are living entities interacting within another living entity, the patient. Phage banks can have an impact by monitoring these complexities during phage therapy. Importantly, phage therapy clinical trials are continuing under existing regulatory frameworks and with products manufactured under GMP (Good Manufacturing Practices).

Backgound/Objective: Novel compounds for mitigating globally growing microbial resistance to antibiotics have been recently more actively researched. Triviron is a polycationic amphiphile synthetic compound with a ribonuclease activity and is used as an antiviral in veterinary medicine. Methods: We studied the effect of triviron on the mouse (line Balb/c) fecal bacteriobiome at different time points (0, 5, 25, and 120 h after a single intragastrical administration) by using amplicon sequence diversity of the V3/V4 region of 16S rRNA genes. Results: Most of the operational taxonomic units (OTUs) belonged to Bacillota (1168 OTUs, i.e., 56% of the total number of OTUs in the study) and Bacteroidota (354, i.e., 17%), with the phyla together accounting for more than 90% of the total number of sequence reads. We found changed relative abundance of some bacterial taxa with time, including the dominating Bacteroidota and Bacillota phyla; some of the changes were sex-related, although at the start of the experiment, there were no difference between the sexes in their fecal bacteriobiome composition and structure. Conclusions: The results unequivocally demonstrated that in mice, feces bacterial community structure was affected by a one-time triviron administration, even at the highest hierarchical level of phyla. The finding that the core dominant phyla can be affected, with the effect lasting at least for five days, implies that some major and important functions of the gut microbiota can be affected as well.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, disabling disorder of unknown etiology, poor prognosis, and limited therapeutic options. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA) was shown to exert resolving effects in IPF, offering a promising alternative for treating this disease; however, the molecular mechanisms associated with this effect have not been explored. Objetive: We evaluated the potential antifibrotic mechanisms of 3′5-DMBA by network pharmacology (NP) and molecular docking (MD). Methods: 3′5-DMBA-associated targets were identified by screening in SwissTargetPrediction. IPF-associated targets were identified using lung tissue meta-analysis and public databases. Common targets were identified, and a protein–protein interaction (PPI) network was constructed; we ranked the proteins in the PPI network by topological analysis. MD validated the binding of 3′5-DMBA to the main therapeutic targets. Results: A total of 57 common targets were identified between 3′5-DMBA and IPF; caspase 8, 9, 3, and 7; myeloid leukemia-induced cell differentiation protein Mcl-1; and poly [ADP-ribose] polymerase 1 are primary targets regulating PPI networks. Functional analysis revealed that the common targets are involved in the pathological features of tissue fibrosis and primarily in the apoptotic process. MD revealed favorable interaction energies among the three main targets regulating PPI networks. Conclusions: NP results suggest that the antifibrotic effect of 3′5-DMBA is due to its regulation of the pathological features of IPF, mainly by modulating signaling pathways leading to apoptosis, suggesting its therapeutic potential to treat this disease.

Background: The recurring actions and intrusive thoughts that characterise obsessive–compulsive disorder (OCD), a long-term mental illness, are known as compulsions. The cornerstones of conventional treatment are psychological counselling and prescribed medication; nonetheless, interest in complementary therapies has grown. This review looks at how well Ashwagandha, curcumin, milk thistle, valerian root, and St. John’s wort may help with OCD symptoms. Methods: To assess these herbal supplements’ potential for therapeutic benefit, case reports and clinical trials were examined. Results: Curcumin, which contains anti-inflammatory and neuroprotective properties, has shown promise in reducing the severity of OCD symptoms. Traditionally used to treat depression, St. John’s wort has shown some potential in lowering anxiety and compulsive behaviour. The herb milk thistle, which is mainly used for liver protection, did not affect OCD symptoms. Anxiolytic valerian root barely offered relief from symptoms associated with anxiety; it has only little effect on obsessions and compulsions. The adaptive Ashwagandha has demonstrated a great deal of promise in lowering stress and enhancing general well-being, which may help with symptom alleviation. Although the initial results are favourable, larger scale randomised controlled trials are necessary to validate reliability and efficacy. Conclusion: This study illustrates how herbal supplements may be used in addition to conventional medications as adjunctive treatments for OCD.

Breast cancer (BC) is the most prevalent form of malignancy among women on a global scale, ranking alongside lung cancer. Presently, conventional approaches to cancer treatment include surgical procedures followed by chemotherapy or radiotherapy. Nonetheless, the efficacy of these treatments in battling BC is often compromised due to the adverse effects they inflict on healthy tissues and organs. In recent times, a range of nanoparticles (NPs) has emerged, exhibiting the potential to specifically target malignant cells while sparing normal cells and organs from harm. This has paved the way for the development of nanoparticle-mediated targeted drug delivery systems, holding great promise as a technique for addressing BC. To increase the efficacy of this new method, several nanocarriers including inorganic NPs (such as magnetic NPs, silica NPs, etc.) and organic NPs (e.g., dendrimers, liposomes, micelles, and polymeric NPs) have been used. Herein, we discuss the mechanism of NP-targeted drug delivery and the recent advancement of therapeutic strategies of organic and inorganic nanocarriers for anticancer drug delivery in BC. We also discuss the future prospects and challenges of nanoparticle-based therapies for BC.

This work is based on research aiming to extract and identify flavonoids from jaborandi (Pilocarpus microphyllus) leaves and investigate their antioxidant and acute antinociceptive capacity. Characterization of the constituents of the ethyl acetate fraction (EtOAcF) obtained from the methanolic extract (ME) was performed by UV-Vis spectrophotometry, infrared spectroscopy, high-performance liquid chromatography (HPLC), mass spectrometry (MS), and cyclic voltammetry, demonstrating the possible majority component of this fraction, the flavone chrysin. Its solubility properties in HPLC are very close to those of the flavonol quercetin, revealing the characteristic presence of this group. An MS spectrum of the fraction revealed a major protonated molecule of m/z 254.9 [M+H]+. The EtOAcF fraction showed three oxidation processes at 0.32 V, 0.54 V, and 0.73 V vs. Ag/AgCl. Three reduction processes at the respective potentials: 0.60 V, −0.03 V, and -0.24 V vs. Ag/AgCl, indicating potential antioxidant activity. At DPPH and ABTS antioxidant radical capture assay, The IC50 obtained was 0.5 mg/mL and 0.81 mg/mL, respectively. In vivo test to determine the mechanical nociceptive threshold in the von Frey test, the dose of 100 mg/kg of the EtOAcF was able to cause inhibition of behavioral changes in neuropathy. The results obtained in this study demonstrate the biological potential of an EtOAcF derived from jaborandi leaves.

Respiratory viruses present significant global health challenges due to their rapid evolution, efficient transmission, and zoonotic potential. These viruses primarily spread through aerosols and droplets, infecting respiratory epithelial cells and causing diseases of varying severity. While traditional intramuscular vaccines are effective in reducing severe illness and mortality, they often fail to induce sufficient mucosal immunity, thereby limiting their capacity to prevent viral transmission. Mucosal vaccines, which specifically target the respiratory tract’s mucosal surfaces, enhance the production of secretory IgA (sIgA) antibodies, neutralize pathogens, and promote the activation of tissue-resident memory B cells (BrMs) and local T cell responses, leading to more effective pathogen clearance and reduced disease severity. Bacillus subtilis spore surface display (BSSD) technology is emerging as a promising platform for the development of mucosal vaccines. By harnessing the stability and robustness of Bacillus subtilis spores to present antigens on their surface, BSSD technology offers several advantages, including enhanced stability, cost-effectiveness, and the ability to induce strong local immune responses. Furthermore, the application of BSSD technology in drug delivery systems opens new avenues for improving patient compliance and therapeutic efficacy in treating respiratory infections by directly targeting mucosal sites. This review examines the potential of BSSD technology in advancing mucosal vaccine development and explores its applications as a versatile drug delivery platform for combating respiratory viral infections.

Background: Staphylococcus aureus is a pathogen that has become resistant to different antibiotics, which makes it a threat to human health. Although the first penicillin-resistant strain appeared in 1945, nowadays, there are just a few alternatives to fight it. To circumvent this issue, novel approaches to develop drugs to target proteins of the bacteria cytoskeleton, essential for bacteria’s binary fission, are being developed. FtsZ and FtsA are two proteins that are key for the initial stages of binary fission. On one side, FtsZ forms a polymeric circular structure called the Z ring; meanwhile, FtsA binds to the cell membrane and then anchors to the Z ring. According to the literature, this interaction occurs within the C-terminus domain of FtsZ, which is mainly disordered. Objective: In this work, we studied the binding of FtsZ to FtsA using computational chemistry tools to identify the interactions between the two proteins to further use this information for the search of potential protein-protein binding inhibitors (PPBIs). Methods: We made a bioinformatic analysis to obtain a representative sequence of FtsZ and FtsA of Staphylococcus aureus. With this information, we built homology models of the FtsZ to carry out the molecular docking with the FtsA. Furthermore, alanine scanning was conducted to identify the key residues forming the FtsZ–FtsA complex. Finally, we used this information to generate a pharmacophore model to carry out a virtual screening approach. Results: We identified the key residues forming the FtsZ-FtsA complex as well as five molecules with high potential as PPBIs.

Fragment libraries have a major significance in drug discovery due to their role in de novo design and enumerating large and ultra-large compound libraries. Although several fragment libraries are commercially available, most are derived from synthetic compounds. The number of fragment libraries derived from natural products is still being determined. Still, they represent a rich source of building blocks to generate pseudo-natural products and bioactive synthetic compounds inspired by natural products. In this work, we generated and analyzed a fragment library of natural products from Colombia, a highly diverse geographical region where fragment libraries are yet to be reported. We also generated and reported fragment libraries of three novel natural product libraries and, as a reference, the most updated version of FDA-approved drugs. In line with the principles of open science, the fragment libraries developed in this study are freely available.

Pomolic acid (3-beta,19alpha-Dihydroxy-urs-12-en-28-oic acid, PA) is a naturally occurring pentacyclic triterpenoid. Derived from the mevalonate pathway through cyclization of 2,3-oxidosqualene, it has been widely found in several plant species. In the mid-1960s, PA was identified as the genuine aglycone of triterpenoid saponins from Sanguisorba officinalis, and studies on its biological activities began in 1989. Since then, several pharmacological properties have been described for this compound, including antitumoral activity. PA induced cell death in tumors, such as lung, brain, breast, and sensitive and resistant leukemia. Additionally, PA modulates resistant proteins and events involved in metastasis. Even though PA constitutes an important candidate for new treatment against several cancers, its availability hampers the evolution of PA studies toward clinical evaluation. This review discusses the limitations of PA availability, the recent approaches to improve it, and other aspects of the antitumoral studies on PA activity.

Background: Ovarian cancer (OC) is the most prevalent gynecological malignancy in women, often diagnosed at an advanced stage due to the absence of specific clinical biomarkers. Notch signaling, particularly Notch3, is frequently activated in OC and contributes to its oncogenic role. Despite its known association with poor clinical outcomes, the biomarker potential of Notch3 remains inadequately explored. Methods: We investigated the biomarker potential of Notch3 in OC using multiple databases, including ONCOMINE, GEPIA, Human Protein Atlas, UALCAN, Kaplan–Meier Plotter, and LinkedOmics. We analyzed Notch3 expression levels, survival correlations, and clinicopathological parameters. Results: Notch3 expression was significantly upregulated in OC, as well as other cancers. Correlation analysis demonstrated that high Notch3 mRNA levels were associated with poor overall survival (OS) (p < 0.05) and relapse-free survival (p < 0.05) in OC patients. Human Protein Atlas data showed elevated Notch3 protein levels in OC tissues compared to healthy controls. Clinicopathological analysis indicated significant associations between Notch3 expression and patient age (p < 0.5), TP53 mutation status (p < 0.5), and cancer stage (p < 0.1). Additionally, genes such as WIZ, TET1, and CHD4 were found to be co-expressed with Notch3 in OC. Notch3 expression also correlated with immune cell infiltration in OC. Conclusions: Our bioinformatics analysis highlights Notch3 as a potential biomarker for poor prognosis in OC. However, further in vitro and in vivo studies, along with validation using larger tissue samples, are necessary to confirm its biomarker utility.

Background/Objectives: Elevated plasma homocysteine levels constitute a risk factor for vascular and cardiovascular disorders. Ferulic acid (FA), a polyphenol is tested on L-methionine-induced hyperhomocysteinemia (hHcy). The present study investigated the protective effect of ferulic acid (FA) on hyperhomocysteinemia (hHcy) induced changes in hemodynamic, biochemical, anti-oxidant, anti-inflammatory parameters as well as histopathological changes in abdominal aorta and heart. Methodology: The Wistar rats were divided into six groups (n = 6) and treated orally for 36 days. The rats were treated with Met (1 gm/kg) to induce Hcy. They were treated with either standard (Vit. B12 + Folic acid; 15 + 70 mg) or test FA (20/40/60 mg/kg, respectively) post-Met treatment. Homocysteine, cholesterol, lactate dehydrogenase (LDH), creatinine kinase (CK-MB), and liver enzymes were estimated in blood followed by the measurement of hemodynamic parameters. The liver was estimated for antioxidant parameters and nitric oxide (NO). Heart and abdominal aorta were studied histopathologically. Result: Diseased rats showed increased Hcy, cholesterol, LDH, CK-MB, alanine transaminase (ALT), aspartate transaminase (AST), malondialdehyde (MDA), NO, and reduced glutathione (GSH). Following FA treatment, these parameters returned to normal. Atherosclerotic lesions in the aorta were observed in the hHcy group; however, in the FA treatment groups, they were lessened. Conclusions: Ferulic acid reduces oxidative and nitrosive stress, thereby reducing hypercyteinemia and improving the lipid profile. It might be acting by increasing the activity of methylation dependent on S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH), which in turn prevents the formation of Hcy and reduces hHcy. The docking study supports these findings.