Pharmacological Properties Research Articles

Anticancer Effects of Withanolides: In Silico Prediction of Pharmacological Properties.

Withanolides are a class of naturally occurring C-28 ergostane steroidal lactones with an abundance of biological activities, and their members are promising candidates for antineoplastic drug development. The ADMET properties of withanolides are still largely unknown, and in silico predictions can play a crucial role highlighting these characteristics for drug development, shortening time and resources spent on the development of a drug lead. In this work, ADMET properties of promising antitumoral withanolides were assessed. Each chemical structure was submitted to the prediction tools: SwissADME, pkCSM-pharmacokinetics, admetSAR v2.0, and Molinspiration Cheminformatics. The results indicate a good gastrointestinal absorption rate, inability to cross the blood-brain barrier, CYP3A4 metabolization, without inhibition of other P450 cytochromes, high interaction with nuclear receptors, and a low toxicity. It was also predicted for the inhibition of pharmacokinetics transporters and some ecotoxicity. This demonstrates a viability for oral drug development, with low probabilities of side effects.

A generative model for the design of novel inhibitors targeting the PD-1/PD-L1 pathway.

2576 Background: The programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) signaling pathway plays a pivotal role in tumor immunosuppression. However, the design of de novo molecules with precise pharmacological and molecular properties remains a resource-intensive and financially demanding endeavor. It is hypothesized that generative models trained on molecular graph encodings can design novel inhibitors targeting the PD-1/PD-L1 pathway. Objective: This study aims to develop a generative model capable of designing novel, orally bioavailable inhibitors of the PD-1/PD-L1 pathway. Methods: A large language model was pre-trained on 1 million chemical structures derived from the ChEMBL database. Each structure was represented using the Simplified Molecular Input Line Entry System (SMILES) strings, which were further tokenized into discrete atomic and functional group-level tokens. The model employs an Average-Stochastic Gradient Descent Weight-Dropped Long Short-Term Memory (AWD-LSTM) architecture. Transfer learning was applied to fine-tune the pre-trained language model on the target chemical structures, enabling domain-specific adaptation for the desired application space. Results: The model demonstrated robust performance in generating chemically valid, unique, and novel inhibitors targeting the PD-1/PD-L1 pathway. It achieved a validity rate of 97%, a uniqueness rate of 96%, a novelty rate of 95%, and a diversity score of 76.04%. Additionally, the generated molecules exhibited favorable physicochemical properties, including a logarithm of the partition coefficient (LogP) of 4.52, atopological polar surface area (TPSA) of 113.06 Angstrom squared, an average of 9.62 rotatable bonds, 2.77 hydrogen bond donors, and 6.79 hydrogen bond acceptors . Conclusions: A generative model was developed to design novel, orally bioavailable inhibitors of the PD-1/PD-L1 pathway. This approach provides an efficient and automated tool for designing de novo molecules with precise molecular and pharmacological properties, potentially accelerating drug discovery in immuno-oncology.

Oxidative damage to DNA, expression of Mt-1, and activation of repair mechanisms induced by vanadium trioxide in cultures of human lymphocytes.

Oxidative damage to DNA, expression of Mt-1, and activation of repair mechanisms induced by vanadium trioxide in cultures of human lymphocytes.

Aristolochia species (Aristolochiaceae) from the Americas, a review of their traditional medicinal uses, phytochemistry, and pharmacological properties.

Aristolochia species (Aristolochiaceae) from the Americas, a review of their traditional medicinal uses, phytochemistry, and pharmacological properties.

Empowering PARP inhibition through rational combination: Mechanisms of PARP inhibitors and combinations with a focus on the treatment of metastatic castration-resistant prostate cancer.

Empowering PARP inhibition through rational combination: Mechanisms of PARP inhibitors and combinations with a focus on the treatment of metastatic castration-resistant prostate cancer.

From Biofuel to Bioactive Compounds: Investigating Jatropha's Phytochemical and Biological Significance - A Review

Objective: This review study examines Jatropha species' phytochemical and biological features, focusing on their secondary metabolites and biological activities. By integrating current information, the paper aims to support future research. Methods: An extensive PubMed, Scopus, and Web of Science search was conducted using "Jatropha," "phytochemicals," and "biological activity" phrases. Peer-reviewed and relevant papers were selected. Jatropha biological activity and phytochemical profiles were included, but irrelevant, non-English, and unaccessible full-text research was excluded. Results: This review paper shows that a wide variety of secondary metabolites, including terpenes, lignans, flavonoids, coumarins, and alkaloids, have been identified in the Jatropha species. These metabolites have many biological properties, including cytotoxicity, antibacterial, antifungal, anti-inflammatory, anticancerogenic, antiviral, and insecticidal effects. Conclusion: This study covers Jatropha species' phytochemical and pharmacological properties, emphasizing their use as sources of secondary metabolites with high bioactivity. The summarized data effectively guides future investigations of medical applications of compounds obtained from Jatropha species.

AI-driven design of novel PARP inhibitors.

3091 Background: Inhibitors of the Poly (ADP-ribose) polymerase (PARP) family play a role in treating HER2-negative locally advanced or metastatic breast cancer with germline BRCA1/2 (gBRCA) mutations, as well as in the maintenance treatment of gBRCA-associated metastatic pancreatic ductal adenocarcinoma. However, the design of de novo small molecules targeting proteins like PARP remains time consuming and resource intensive. It is hypothesized that generative models trained on molecular graph encodings could accelerate the design of novel PARP inhibitors. Objective:This study aims to develop a generative model capable of designing novel, orally bioavailable PARP inhibitors. Methods: A large language model was pre-trained on 1 million chemical structures sourced from the ChEMBL database. Each structure was represented as a Simplified Molecular Input Line Entry System (SMILES) string, which was tokenized into discrete atomic and functional group-level tokens. The model leverages an Average-Stochastic Gradient Descent Weight-Dropped Long Short-Term Memory (AWD-LSTM) architecture. Transfer learning was applied to adapt the pre-trained model to specific target chemical structures, enabling domain-specific fine-tuning for the de novo design of PARP inhibitors. Results: The model demonstrated robust performance in generating chemically valid, unique, novel, and diverse PARP inhibitors. It achieved a validity rate, uniqueness rate, and novelty rate of 100%, along with a diversity score of 81.53%. Furthermore, the generated molecules exhibited favorable physicochemical properties, including a molecular weight of 417.52 Da, a logarithm of the partition coefficient (LogP) of 2.58, a topological polar surface area (TPSA) of 93.21 Angstrom squared, an average of 4.05 rotatable bonds, 1.84 hydrogen bond donors, and 5.14 hydrogen bond acceptors. Conclusions: A generative model was developed to design novel, orally bioavailable PARP inhibitors. It provides an efficient and automated tool for de novo small molecule design with tailored molecular and pharmacological properties, potentially accelerating the development of PARP inhibitors.

Restoration of skin mucosal immune responses, cyto-genotoxicity and histological alterations in arsenic exposed Labeo rohita by Moringa oleifera supplementation.

Restoration of skin mucosal immune responses, cyto-genotoxicity and histological alterations in arsenic exposed Labeo rohita by Moringa oleifera supplementation.

Exploring the Bioactive Constituents and Pharmacological Activity of Scutellaria baicalensis Georgi, or Chinese Skullcap

Introduction: Scutellaria baicalensis Georgi, a plant with therapeutic properties, has been extensively utilized in China for centuries. The extract derived from its roots is commonly referred to as Huang-Qin. Materials and Methods: The informative data were gathered from many electronic databases, including Scopus, Science Direct, PubMed, and Web of Science. The study criteria for selection included analyzing scientific manuscripts that specifically investigated phytoconstituents and their pharmacological effects. The keywords used were Scutellaria baicalensis, bioactive components, and pharmacological profile. Discussion: The main concern of this study is to enhance the accessibility of extensive research discoveries about the pharmacological potential of S. baicalensis. Results: S. baicalensis root has been utilized to manage dysentery, diarrhea, hypertension, insomnia, inflammation, respiratory infections, and hemorrhaging. Wogonoside and baicalin are the primary bioactive constituents obtained from S. baicalensis root. The flavones have been documented to possess many pharmacological properties, such as hepatoprotective, anti-cancer, antibacterial, antioxidant, antiviral, neuroprotective, and anticonvulsant activities. Conclusion: This manuscript's main concern is to enhance the accessibility of extensive research discoveries about the pharmacological potential of S. baicalensis.

Hibiscus Sabdariffa Linn: Phytochemical Impact on the Mechanism of Neuroprotective and Anti-inflammatory Pathways

The Hibiscus sabdariffa plant is an herbaceous member of the Malvaceae family. It is a widely recognized herb with medicinal properties. It is utilized extensively in many traditional medical practices along with delicious food items, like jams, puddings, and cakes. The purpose of this review was to investigate and compile all of the available data and evidence about the calyxes of Hibiscus sabdariffa with a particular focus on their nutritional composition, bioactive components, and therapeutic benefits. This article provides a comprehensive overview of the plant's traditional usage, pharmacognostic characterization, nutritional and phytochemical composition, and pharmacological properties. This paper elucidates the mechanisms by which Hibiscus sabdariffa exerts neuroprotective and anti-inflammatory effects in managing neurological disorders. Additionally, Hibiscus sabdariffa has been shown to prevent memory impairment, which may be attributed to its effects on neuroinflammation and amyloidogenesis. Hibiscus sabdariffa has been reported to have anti-inflammatory effects due to the presence of polyphenol compounds that possess anti- inflammatory properties. Flavonoids are also commonly found in it, which inhibit the transcription factor nuclear factor kappa B. This plant has a variety of health benefits, including antioxidant, antidepressant, diuretic, antihyperlipidemic, anti-obesity, hepatoprotective, anti-inflammatory, anti-cancer, antimicrobial, and neuroprotective activities. Based on the literature, this review provides a thorough analysis of the pharmacological and phytochemical characteristics of Hibiscus sabdariffa.

Conditioned medium derived from mesenchymal stem cells and spinal cord injury: A review of the current therapeutic capacities.

Conditioned medium derived from mesenchymal stem cells and spinal cord injury: A review of the current therapeutic capacities.

Integrated network pharmacology and experimental validation to elucidate the mechanism of celastrol in mitigating sepsis-induced acute lung injury in mice.

Integrated network pharmacology and experimental validation to elucidate the mechanism of celastrol in mitigating sepsis-induced acute lung injury in mice.

A Review on Synthesis, Characterization, and Pharmacological Properties of Some Sydnone Derivatives

The mesoionic compounds have great importance due to their dipolar nature. They are versatile synthons in synthetic chemistry and possess various chemotherapeutic activity. The most important moiety found in mesoionic compounds is the sydnone ring system. Sydnone derivatives have stimulated much interest among synthetic researchers as a result of their unique dipolar, mesoionic character. This ring system is also associated with a wide variety of biological activities. Sydnones derivatives have various applications synthetic and medicinal chemistry. Sydnones serve as very useful precursors for selective heterocycles (pyrazoles, imidazoles, oxadiazoles, oxazoles, thiazoles, tetrazoles) which has also served to initiate research into their functionalization and cycloaddition chemistry. Which proved stimulated extensive research of sydnones under chemical and its probable industrial applications. So, this mini-review article offers a wide scope of synthesis and applications of sydnones derivatives.

Santali Albi Lignum: From traditional efficacy to pharmacological properties and modern therapeutics applications.

Santali Albi Lignum: From traditional efficacy to pharmacological properties and modern therapeutics applications.

Impact of Fe(III) and Ce(III) ions on pharmacological properties of novel Schiff base ligand: Anticancer, antiviral, antioxidant, anti-fungal investigations from wallpaper, and computational insights

Impact of Fe(III) and Ce(III) ions on pharmacological properties of novel Schiff base ligand: Anticancer, antiviral, antioxidant, anti-fungal investigations from wallpaper, and computational insights

Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor-Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas.

Novel approaches in molecular imaging and targeted therapeutics are transforming the management of renal cell carcinoma (RCC) and urothelial carcinoma (UC). This review focuses on three key areas of innovation: molecular imaging, hypoxia-inducible factor-2α (HIF-2α) inhibition, and antibody-drug conjugates (ADCs). In molecular imaging, prostate-specific membrane antigen positron emission tomography/computed tomography has shown promise in RCC, while novel tracers targeting carbonic anhydrase IX and nectin-4 are emerging for RCC and UC, respectively. These approaches may enable better characterization of disease and treatment response monitoring. HIF-2α inhibition represents a breakthrough in targeting the fundamental pathobiology of clear cell RCC, with belzutifan demonstrating significant clinical benefit in both von Hippel-Lindau disease and sporadic RCC. Next-generation HIF-2α inhibitors, including casdatifan, show promising early clinical results with distinct pharmacologic properties. ADCs have become a cornerstone of UC treatment, with enfortumab vedotin plus pembrolizumab now approved as first-line therapy. Multiple human epidermal growth factor receptor 2 (HER2)-directed ADCs have shown efficacy in HER2-expressing UC, including trastuzumab deruxtecan, which recently received tumor-agnostic approval. While ADC development in RCC faces unique challenges, novel approaches including immunostimulatory payloads and bispecific antibodies are being explored. The integration of these advances in molecular imaging and therapeutics offers opportunities for more personalized treatment approaches in RCC and UC.

Rutin-Associated Hepatoprotection: A Review of Mechanisms and Therapeutic Prospects.

Liver disorders pose a considerable global health challenge, accompanied by rising mortality rates. Current therapeutic strategies, though effective, often face limitations due to adverse effects and therapeutic resistance, prompting the exploration of alternative treatments, particularly safer natural compounds. Rutin, a widely available bioflavonoid, has emerged as a promising candidate owing to its varied pharmacological properties. We conducted a comprehensive search on PubMed and Web of Science using the following keywords: 'rutin', 'liver diseases', 'hepatoprotection', 'clinical observations', 'mechanisms, pharmacology' and various combinations of these terms. This review systematically examines rutin's therapeutic potential in hepatic disorders, focusing on its molecular mechanisms, particularly its effects on inflammatory pathways, oxidative stress and hepatocellular protection. We analyse existing evidence supporting rutin's hepatoprotective efficacy, identify its cellular and molecular targets and evaluate its potential applications in various liver diseases. Our systematic analysis provides theoretical support for developing rutin-based therapies in hepatic disease management and identifies future research directions and clinical applications.

Synthesis of substituted arylsulphonamoyl ‘Leu-Gly’ dipeptide carboxamide derivatives containing antimalarial and other related diseases pharmacological properties

Synthesis of substituted arylsulphonamoyl ‘Leu-Gly’ dipeptide carboxamide derivatives containing antimalarial and other related diseases pharmacological properties

Pharmacological advances and therapeutic applications of niclosamide in cancer and other diseases.

Niclosamide, an FDA-approved drug traditionally used to treat parasitic infections, has garnered remarkable attention for its diverse pharmacological properties, suggesting potential therapeutic utility in oncology and a range of other diseases. This review offers an in-depth analysis of the chemical features and pharmacokinetics of niclosamide, underscoring the role of its salt forms and derivatives in enhancing bioavailability and therapeutic effectiveness. Emerging breakthroughs in nanotechnology have enabled the generation of advanced formulations capable of improving the safety and efficacy of niclosamide, addressing the challenges posed by its poor water solubility. Further, the review explores the intriguing molecular mechanisms driving niclosamide anticancer activity, highlighting its ability to act as a potent mitochondrial uncoupler and precisely modulate critical signal pathways that regulate cell proliferation, apoptosis, and inflammation. In cancer treatment, niclosamide has showcased compelling effects against various malignancies, offering marked potential in overcoming multidrug resistance, particularly in the resistant forms of leukemia and ovarian cancer. Additionally, the drug's versatility broadens its therapeutic potential beyond oncology, encompassing viral infections, metabolic disorders, and anti-inflammatory applications. By integrating the current literature, this review seeks to illuminate the pharmacological and clinical progress of niclosamide, hence emphasizing its promise as a multi-targeted therapeutic agent. As research evolves, niclosamide is poised to play a pivotal role in cancer therapy and the treatment of other complex diseases, reinforcing the necessity for continued clinical exploration and innovation.

Phytochemical and pharmacological properties of the genus Pseudotsuga.

Phytochemical and pharmacological properties of the genus Pseudotsuga.