Current drug discovery technologies最新文献

Rheumatoid arthritis (RA) is an autoimmune disease that features chronic inflammation of the joints, destruction of the synovial tissue, and progressive disability. Traditional treatments with disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids are usually linked to systemic side effects and low therapeutic effi-cacy. Drug delivery systems based on nanotechnology have been presented as a valuable strategy for the improvement of drug bioavailability, toxicity decrease, and targeted treatment of RA. This review discusses the latest developments in nanotechnology-based drug delivery systems, such as liposomes, niosomes, nanoemulsions, solid lipid nanoparticles, ethosomes, and transferosomes, focusing specif-ically on transdermal drug delivery systems (TDDS). These nanocarriers provide long-term release of the drug, enhanced permeability, and enhanced therapeutic activity by more targeted delivery to inflamed areas. In addition, the combination of combination therapy, co-delivery approaches, and phototherapy has also exhibited synergistic effects to evade drug resistance and improve anti-inflam-matory activity. Despite these developments, formulation stability, industrial manufacturing, and clinical translation remain critical challenges. Additional studies and clinical evidence are required to maximize nanotechnology-based therapies and integrate them into RA therapy.

A game-changing strategy in precision medicine is theranostics, which is the combination of diagnostics and treatments on one platform. Microrobots have drawn a lot of interest as promising agents in theranostic applications because of their small size, agility, and multifunctionality. This anal-ysis highlights the potential of microrobots to transform illness management by examining how they can integrate precise medicine delivery and diagnostic capabilities. Advanced features like imaging for focused diagnostics, payload delivery for precision therapies, and biosensing for real-time disease monitoring can be built into microrobots. These microrobots can navigate intricate biological environ-ments and provide localized intervention at the cellular and subcellular levels. They are propelled by external pressures such as magnetic fields or biological mechanisms. Recent advancements in micro-robots, including biocompatible polymers and stimuli-responsive systems, offer potential for early dis-ease identification and targeted drug release in neurological, cardiovascular, and malignant diseases. Along with solutions, issues like scalability, regulatory approval, and biocompatibility are also cov-ered. With an emphasis on their role in influencing the development of integrated healthcare solutions, this paper offers a thorough summary of technological developments and potential applications of mi-crorobots in theranostics. The study authors examined databases such as PubMed, Scopus, Google Scholar, and Web of Science for peer-reviewed articles published within the last 10 years on theranostic microrobots, diagnostic tools, drug delivery systems, and precision medicine. It comprised empirical research on microrobot design, functioning, therapeutic applications, diagnostic capabilities, treatment results, and safety profiles. This methodical methodology found patterns, gaps, and advances in the discipline.

Nowadays, a wide range of aromatic heterocyclic compounds are employed as therapeutics. Among these, pyrimidine is a well-known nucleus with two nitrogen atoms at the first and third positions of six-membered rings, with the chemical formula C4H4N2. In 1885, a physicist named Pinner coined the term "pyrimidine," which originates from "pyridine" and "amidine." Pyrimidine and its substituents have a variety of pharmacological and biological features. Research, drug discovery, and screening utilise the potential of this chemical substance. Significant therapeutic features such as antihypertensive, antimicrobial, anti-inflammatory, antimalarial, antihistaminic, sedatives and hypnotics, anticancer, and anti-human immunodeficiency virus (HIV) can be seen in the pyrimidine- containing compounds, as demonstrated by the literature. Search engines like Google, Google Scholar, ResearchGate, and ScienceDirect were used to obtain the information. In the future, in addition to helping with drug design and the development of pyrimidine derivatives as therapeutic drugs, this review paper offers insight into the different biological responses of compounds generated from pyrimidine.

Fifty percent of people worldwide suffer from periodontitis, a chronic inflammation of the soft tissue that surrounds the teeth. Effective filling of dental pockets is paramount for successful treatment outcomes in periodontal therapy. This review examines all the important aspects of in situ-forming dental cement for filling dental pockets. It focuses on the effectiveness of in-situ forming dental cement in filling periodontal pockets, the conditions necessary for their retention, their inter-action with the periodontal environment, and their potential performance in clinical practice. Through an in-depth analysis of current literature and clinical evidence, this review highlights the promising role of in-situ forming dental cement in enhancing periodontal therapy outcomes. The effectiveness of various filling systems, such as thermosensitive hydrogels, in-situ gel systems, microparticulate systems, and in-situ forming implants, is critically examined in this study. The advantages and dis-advantages of each system are thoroughly examined, with a focus on their clinical uses and efficacy in the treatment of periodontitis. It explains the essential requirements for these cements in the peri-odontal environment, such as low viscosity for simple administration, the right setting time for sta-bility, and regulated drug release mechanisms to sustain therapeutic concentrations over time. Along-side issues with formulation stability and biocompatibility, the suitability of these materials for the unique conditions present in periodontal pockets is assessed. In order to optimize these materials for better therapeutic effects and enhanced outcomes for patients in periodontal therapy, this study out-lines potential directions for future research. It highlights the potential of in-situ forming dental ce-ment to transform periodontal treatment by combining recent research findings with practical appli-cations.

Background: The quantitative structure-property relationship (QSPR) modelling can be helpful in the in-silico prediction and pre-determination of the drug permeability values of a large number of compounds through human intestinal enterocytes for screening of potential candidate drugs, thereby enhancing oral drug development.

Methods: The present study involved the development of a regression-based QSPR model for the prediction of Caco-2 cell-permeability values of compounds. The training of the model was carried out on a novel large dataset of 1272 compounds with 30 selected 2D descriptors.

Results: An R2 value of 0.96 suggested that the model was significant. Finally, the model was applied in the virtual screening of 49,430 potential compounds of the CAS database of antiviral compounds, among which the model successfully screened 100 compounds as potential leads, with 96 compounds falling within the Applicability Domain (AD).

Conclusion: The present study highlights in-silico screening, which could be beneficial for the early stages of drug development.

Introduction: The global burden of tuberculosis (TB) remains a major concern for society that is worsening day by day with the emergence of drug-resistant TB as well as risks associated with latent TB. Isocitrate lyase (ICL) has been shown as a potential target that plays a role in the la-tent/dormant stage of M. tuberculosis. Several inhibitors against ICL have been designed and tested, which have various side effects.

Methodology: This study focuses on the phytochemicals from plant extracts, which have anti-tuber-cular properties. A total of 1413 phytochemicals were virtually screened against ICL to identify the promising therapeutic compounds. The top four lead phytochemicals were selected based on their binding energy and subjected to redocking and intermolecular interaction analysis. These results were further validated through 100 ns MD simulation to check the stability of these complexes. The find-ings of these complexes were compared to the reference compound VGX.

Results: The top selected compound viz., Allantoin, Gallic acid, Citric acid, and 3,5-Dihydroxyben-zoic acid from virtual screening result displayed better docking score ranging from -8 kcal/mol to -7.2 kcal/mol than the reference compound VGX (-7.5 kcal/mol). Moreover, during the MD simula-tion analysis, gallic acid exhibited greater stability compared to all other compounds, including the reference compound.

Conclusion: Among selected phytochemicals, gallic acid exhibited highest stability and binding af-finity within the active site of ICL as compared to previously identified compounds, which suggests that it is as potential candidate against ICL. That can be used for further in vitro and in vivo studies to evaluate its effectiveness against TB.

Background: Capecitabine is an anticancer antimetabolite of fluorouracil that inhibits cell proliferation and impairs DNA repair in cancer cells. It is given specifically to treat metastatic breast, gastric and colorectal cancers.

Objective: To design, formulate, optimize and evaluate Capecitabine Nanosuspension using the QbD Box-Behnken model.

Methods: Deploying the Box-Behnken Design (BBD) model, Capecitabine nanosuspension was for-mulated with seventeen runs; the independent variables selected are Pullulan concentration, Poloxamer F407 concentration, and sonication time. The developed nanosuspension was evaluated for particle size, Zeta potential, entrapment efficiency, in vitro drug release, and anti-cancer effectiveness. Drug-excipient compatibility was assessed using the Fourier transform infrared spectroscopy method. X-ray Diffraction studies and Differential Scanning Calorimetry were used to perform and assess the crys-talline nature. Additionally, characteristics of the developed nanosuspension were assessed by per-forming a scanning electron microscopy study.

Results: The effect of various factors on key responses, namely particle size, entrapment efficiency, and drug release up to 8 hours, was assessed. A polynomial equation was employed through the anal-ysis to optimize the formulation, considering the significance levels indicated by the p-values. Notably, these variables demonstrated a substantial influence on the responses. The comparison between ob-served and predicted values revealed a relatively minor variance (85.90, 69.57, and 76.34 for particle size, entrapment efficiency, and percentage drug release at 8 hours, respectively), indicating the mod-el's suitability. The prepared nanosuspension exhibited compatibility with the used excipients, with capecitabine-entrapped nanoparticles uniformly dispersed within the suspending medium.

Conclusion: Developed capecitabine nanosuspension demonstrated better efficacy and effectiveness against gastric cancer, with independent variables like pullulan and Poloxamer F207 concentration, along with sonication time, influencing particle size, entrapment efficiency, and drug release.

Alginate, a naturally occurring polysaccharide, exhibits immense potential for diverse ap-plications due to its ability to undergo chemical modifications and blend with other constituents. These modifications enable the creation of alginate derivatives that are not only biocompatible for biomedical and tissue engineering applications but also crucial for the thriving field of bioelectronics. Alginate derivatives serve multiple functions, including their use in wound dressings, scaffolds for drug delivery and tissue engineering, as well as key components in hydrogel formulations. Recent studies highlight the immunomodulatory properties of alginate and its derivatives, including porphy-rans, fucoidan, and chitin. These materials enhance the innate immune system, rebalance the Th1/Th2 ratio towards Th1, reduce IgE synthesis, and inhibit mast cell degranulation, alleviating allergic symptoms. In pharmaceuticals, alginate-based materials are utilised as substitutes and bio-linkers in 3D bioprinting, demonstrating their potential for creating complex tissue constructs. This review un-derscores the fundamental characteristics of alginates, outlines various chemical modification meth-odologies, and discusses recent developments in the fabrication of functional alginate-based compo-sites. By presenting this synthesis of relevant information, we aim to inspire further scientific break-throughs in the development of biocompatible electronic devices and intelligent materials.

Background: The search for potent anticancer agents has accelerated the evaluation of a wide variety of pharmacological scaffolds, including oxazole derivatives. Although they are currently underexplored, they are promising as anticancer agents. This research covers the synthesis and structure-activity relationships of oxazole-based compounds.

Methods: The authors designed and synthesized new oxazole derivatives and screened them for their anticancer activity using both computational and experimental methods. Molecular docking studies were performed to identify possible targets based on literature and the interaction of these molecules with anticancer targets like c-Kit tyrosine kinase (TRK) and MDM2. The compounds were tested using the MTT assay on a panel of different cancer cell lines, including MCF-7, to evaluate their potential effectiveness.

Results: Optimized and robust synthetic procedures were developed for oxazole-based Schiff bases, with their structures confirmed through spectral analyses. Compounds 4a-e exhibited significantly stronger anticancer activity, suggesting some Structure-Activity Relationship (SAR) nuances within the series. The biological activities (IC₅₀) were determined to be in the range of 80-100 μg/mL, while molecular docking indicated that compound 4c could serve as a potential lead for c-Kit Tyrosine Kinase (TRK) inhibition.

Conclusion: The results obtained from the present study corroborate the hypothesis that oxazole derivatives are potent anticancer agents, consistent with predictions from molecular docking studies. These findings highlight the significance of the oxazole scaffold in anticancer drug discovery and encourage further exploration of structure-activity relationships to enhance therapeutic potential. Although compound 4c showed better interactions in docking studies compared to biological screening, this suggests that pharmacokinetic issues should be addressed. Future studies are likely to include in vivo models and detailed mechanistic evaluations to validate these findings and support the development of oxazole-derived anticancer compounds.

Objective: This manuscript, aimed to prepare a scientific report, underscores the pharma-cotherapeutic aspects, including therapeutic indications, mechanisms of therapeutic action, pharma-cokinetics, adverse reactions, safety in special cases, approximate costs, etc., of USFDA-approved novel drugs in the year 2023 and serve as a treasured resource for academia, researchers, patients, and clinicians.

Methods: This comprehensive report was prepared by reviewing the pre-clinical and clinical data of the USFDA-approved novel drugs available in the public domain, especially on the website of the USFDA, National Library of Medicine, Clinical Trials, other online resources, and cross-references.

Results: The USFDA has approved 55 novel drug therapies in the year 2023 and identified 38 drugs as new chemical entities (29 small molecules, 5 peptides, and 4 oligonucleotides) and 17 new biologics. About 51% (28 out of 55) of drugs were recommended for rare diseases and designated as orphan drugs. In addition to the therapeutic aspects and general description, the approximate cost or price and safety studies in special cases such as lactating and pregnant women, pediatrics, and geriatrics of all novel drug therapies are meticulously presented in the manuscript.

Conclusion: The novel drug therapies approved by the USFDA hold significant potential to enhance the patient's care by providing advanced treatment modalities. This manuscript, reporting the comprehensive description of therapeutic aspects of the mentioned new drug therapies, underscores the commitment of the pharmaceutical sector to address the unmet medical needs and reshape the landscape of the healthcare service system by instilling optimism among patients and healthcare providers.