Drugs Drug Candidates, Volume 4, Issue 1 (March 2025) – 12 articles

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

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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). Full article