Pharmaceuticals最新文献

{"title":"Advances in Molecular Function and Recombinant Expression of Human Collagen.","authors":"Wenli Sun, Mohamad Hesam Shahrajabian, Kun Ma, Shubin Wang","doi":"10.3390/ph18030430","DOIUrl":"10.3390/ph18030430","url":null,"abstract":"<p><p>Collagen is the main protein found in skin, bone, cartilage, ligaments, tendons and connective tissue, and it can exhibit properties ranging from compliant to rigid or form gradients between these states. The collagen family comprises 28 members, each containing at least one triple-helical domain. These proteins play critical roles in maintaining mechanical characteristics, tissue organization, and structural integrity. Collagens regulate cellular processes such as proliferation, migration, and differentiation through interactions with cell surface receptors. Fibrillar collagens, the most abundant extracellular matrix (ECM) proteins, provide organs and tissues with structural stability and connectivity. In the mammalian myocardial interstitium, types I and III collagens are predominant: collagen I is found in organs, tendons, and bones; collagen II is found in cartilage; collagen III is found in reticular fibers; collagen IV is found in basement membranes; and collagen V is found in nails and hair. Recombinant human collagens, particularly in sponge-like porous formats combined with bone morphogenetic proteins, serve as effective scaffolds for bone repair. Due to their biocompatibility and low immunogenicity, collagens are pivotal in tissue engineering applications for skin, bone, and wound regeneration. Recombinant technology enables the production of triple-helical collagens with amino acid sequences identical to human tissue-derived collagens. This review summarizes recent advances in the molecular functions and recombinant expression of human collagens, with a focus on their biomedical applications.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically Based Pharmacokinetic Modeling of Tofacitinib: Predicting Drug Exposure and Optimizing Dosage in Special Populations and Drug-Drug Interaction Scenarios.","authors":"Zhihai Cao, Zilong Wang, Qian Zhang, Wei Zhang, Liang Zheng, Wei Hu","doi":"10.3390/ph18030425","DOIUrl":"10.3390/ph18030425","url":null,"abstract":"<p><p><b>Background:</b> Tofacitinib is mainly used in the adult population for immune-mediated inflammatory diseases. There is little information available on the pharmacokinetics of tofacitinib in pediatric patients, populations with hepatic impairment and renal impairment, and patients with drug-drug interactions (DDIs). This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of tofacitinib in the populations mentioned above. <b>Methods:</b> We developed the PBPK models in PK-Sim^® and evaluated the models with observed clinical PK data. The Monte Carlo algorithm was used for parameter identification. <b>Results:</b> The adult PBPK model accurately simulated the pharmacokinetic profiles of all administration scenarios. The geometric mean fold errors for the predicted/observed maximum concentration and area under the curve are 1.17 and 1.16, respectively. The extrapolated models accurately simulated the pharmacokinetic characteristics of tofacitinib. The pediatric patients aged 12-to-<18 years and 2-to-<6 years need to adjust the dose to 4 mg BID and 1.7 mg BID, respectively, to achieve comparable steady-state exposures to 5 mg BID in adults. The populations with moderate hepatic impairment and severe renal impairment need to reduce the dose to 50% and 75% of the original dose, respectively. Tofacitinib should be reduced to 50% and 65% of the original dose for concomitant use with fluconazole and ketoconazole, respectively, and increased to 150% of the original dose for concomitant use with rifampicin. <b>Conclusions:</b> We developed a tofacitinib PBPK model and extrapolated it to special populations and DDIs. The predictive results of the models can help the rational use of tofacitinib in these populations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molluscicidal and Schistosomicidal Activities of 2-(1<i>H</i>-Pyrazol-1-<i>yl</i>)-1,3,4-thiadiazole Derivatives.","authors":"Leonardo da Silva Rangel, Daniel Tadeu Gomes Gonzaga, Ana Cláudia Rodrigues da Silva, Natalia Lindmar von Ranke, Carlos Rangel Rodrigues, José Augusto Albuquerque Dos Santos, Nubia Boechat, Keyla Nunes Farias Gomes, Guilherme Pegas Teixeira, Robson Xavier Faria","doi":"10.3390/ph18030429","DOIUrl":"10.3390/ph18030429","url":null,"abstract":"<p><p><b>Background/objectives:</b> Schistosomiasis is caused by flatworms of the genus <i>Schistosoma</i>, for which mollusks of the genus <i>Biomphalaria</i> are intermediate hosts. Niclosamide (NCL) is a molluscicide recommended by the World Health Organization (WHO) for control of <i>Biomphalaria</i>. Although effective, it is expensive and environmentally toxic, which raises concerns regarding its widespread use. As a result, we explored new synthetic substances as alternative strategies for controlling <i>Biomphalaria glabrata</i>. We evaluated the molluscicidal activity of 2-(1<b><i>H</i></b>-py-razol-1-<b><i>yl</i></b>)-1,3,4-thiadiazole and 2-(4,5-dihydro-1<b><i>H</i></b>-pyrazol-1-<b><i>yl</i></b>)-1,3,4-thiadiazole derivatives against <i>B. glabrata</i> snails and embryos, as well as <i>Schistosoma</i> cercariae (infective larvae). <b>Methods:</b> Adult and young snails were added to 24-well plates containing 20 synthetic compounds from the PDAN series for initial screening over 96 h at a concentration of 100 ppm. Water and NCL (2 ppm) were used as the negative and positive controls, respectively. Active compounds in the adult <i>B. glabrata</i> assay were selected for the tests vs. embryos and cercariae. <b>Results:</b> In the initial screen, only PDAN 52 (63 ± 4%) and 79 (12 ± 3%) showed molluscicidal activity at a concentration of 100 ppm up to 48 h. Consequently, we selected only PDAN 52. The LC₅₀ value found in the tests on embryos after 24 h of treatment was 20 ± 2 ppm and, after 48 h, it was 4 ± 0.5 ppm. Against cercariae, we measured an LC₅₀ value of 68 ± 5 ppm after 4 h of treatment. PDAN 52 did not induce marked toxicity against a second mollusk, <i>Physella acuta</i>, after 48 h of exposure. <b>Conclusions:</b> We highlight the promising molluscicidal activity of PDAN 52 against different developmental stages of the mollusk, <i>B. glabrata</i>, as well the infective larvae of <i>Schistosoma mansoni</i>.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wuzhuyu Decoction Relieves Chronic Migraine by Regulating 5-HT1A and 3A Receptors-Mediated CREB Signaling Pathway in Brain and Intestine.","authors":"Zhimin Song, Meijing Li, Ziwei Zhou, Xiaomeng Guo, Qi Wang, Zekuan Zhang, Keshu Wang, Qixiang Zheng, Wenjing Gou, Sha Wu, Hui Zhao, Muxin Gong","doi":"10.3390/ph18030426","DOIUrl":"10.3390/ph18030426","url":null,"abstract":"<p><p><b>Background:</b> Chronic migraine (CM) is a common complex nervous system disease, often accompanied by symptoms of the digestive tract that interact with each other, leading to prolonged and difficult-to-cure migraines. These symptoms are associated with abnormalities in 5-HT and its receptors. Wuzhuyu decoction (WZYD) is a traditional Chinese medicine prescription commonly used in clinics to treat CM; it relieves gastrointestinal symptoms, such as nausea and vomiting; however, its mechanism is still unclear. Investigating the differences in the role of WZYD compared to existing drugs targeting 5-HT receptors in the treatment of CM not only helps elucidate its pathogenesis but also provides possibilities for the development of new therapeutic approaches. <b>Methods:</b> An inflammation soup (IS)-induced CM male rat model was established. Based on a preliminary experiment, the target of WZYD in treating CM was determined by network pharmacology, and verified by molecular docking. ELISA, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the expression levels of CM-related indicators (5-HT, calcitonin gene-related peptide (CGRP), and c-Fos) to ensure the successful establishment of the CM model and the effectiveness of the drug. On this basis, the protein expression levels of 5-HT1A/3A receptors and their cAMP-response element binding protein (CREB) signaling pathway were detected by western blot and immunohistochemistry. The role of 5-HT1A/3A receptors in the treatment of CM by WZYD was validated using a 5-HT1A receptor antagonist (WAY 100635) and a 5-HT3A receptor agonist (SR 57227). <b>Results:</b> The results showed that WZYD increased the expression of 5-HT in the brain, decreased the expression of CGRP, c-Fos, ionized calcium-binding adapter molecule 1 (Iba1), and relieved CM. At the same time, WZYD also increased the expression of the 5-HT1A receptor and decreased the expression of the 5-HT3A receptor in the brain and colon of CM rats. Subsequently, WZYD further exerted its brain-gut integrated therapeutic effects by regulating the CREB signaling pathway mediated by 5-HT1A/3A receptors in the brain and colon of CM rats. <b>Conclusions:</b> WZYD not only regulates neurotransmitters in the brain and colon at the same time, but also specifically regulates 5-HT1A/3A receptors in the brain and colon, which explains the characteristics and advantages of WZYD from a new perspective. While effectively relieving headache symptoms, it also improves related gastrointestinal symptoms, which is more conducive to the treatment of CM.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huafengdan Inhibits Glioblastoma Cell Growth and Mobility by Acting on PLAU and CAV1 Targets.","authors":"Dengxiao Lin, Wenfeng Yu, Jia Yu, Sha Cheng, Yu Song, Xiaoqing Wan, Yingjiang Xu, Heng Luo, Baofei Sun","doi":"10.3390/ph18030428","DOIUrl":"10.3390/ph18030428","url":null,"abstract":"<p><p><b>Background</b>: Glioblastoma (GBM) is considered a clinically refractory malignant tumor due to its high recurrence and malignancy, invasiveness, and poor prognosis. The ethnomedicine Huafengdan (HFD) is prepared using several Chinese herbs by a complex fermentation process that has a long history. Previous studies have reported the inhibitory effect of HFD on GBM both in vitro and in vivo; however, its mechanism of action is unclear. <b>Methods</b>: The inhibitory effects of HFD on the growth, migration, and invasion of GBM cells were determined using the MTT assay, EdU assay, Transwell assay, flow cytometry, and Western blotting. A subcutaneous graft tumor model of nude BALB/c mice was established using U87 cells, and the in vivo activity and toxicity of HFD were evaluated using immunohistochemical staining and hematoxylin and eosin staining. Network pharmacology, bioinformatics, and transcriptomics were used to screen the targets and related signaling pathways of HFD in GBM and were validated using qPCR, CETSA, and Western blotting. <b>Results</b>: HFD inhibited the proliferation, invasion, and migration of GBM cells and induced S-phase block and apoptosis in GBM cells. It inhibited the in vivo growth of GBM cells without obvious toxicity. Mechanistic studies showed that the inhibition of GBM cell growth, migration, and invasion by HFD involved the key targets PLAU and CAV1. Its associated signaling pathways were the PI3K/Akt signaling pathway and cell cycle signaling pathway. <b>Conclusions</b>: Our findings confirm the novel function of HFD in inhibiting GBM cell growth in vitro and in vivo and highlight its potential in treating GBM.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Efficacy and Toxicity Assessment of an Amphotericin B Gel for the Treatment of Cutaneous Leishmaniasis.","authors":"Lilian Sosa, Lupe Carolina Espinoza, Marcelle Silva-Abreu, Ximena Jaramillo-Fierro, Diana Berenguer, Cristina Riera, María Rincón, Ana C Calpena","doi":"10.3390/ph18030427","DOIUrl":"10.3390/ph18030427","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Leishmaniasis is a neglected tropical disease caused by a protozoan parasite of <i>Leishmania</i>. This study aimed to evaluate the in vitro efficacy and toxicity of a previously developed amphotericin gel as a possible treatment for cutaneous leishmaniasis. <b>Methods</b>: First, quality control of the AmB-gel was carried out, including microbiological stability. The permeated and retained drug was tested on healthy and lacerated human skin. Tolerance to the AmB-gel was tested in vitro using HaCaT, RAW 264.7, and J774 cell lines and by an irritation test (HET-CAM). Promastigotes and amastigotes of various <i>Leishmania</i> species were tested, and the microscopic morphology of promastigotes exposed to the formulation was analyzed. Computational analysis was performed on the drug, polymer, and ergosterol in the promastigote. <b>Results</b>: The AmB-gel presented appropriate characteristics for topical use, including no microbial contamination after storage. The amount of drug retained on the intact and injured skin was 1180.00 ± 13.54 µg/g/cm² and 750.18 ± 5.43 µg/g/cm², respectively. The AmB-gel did not cause significant signs of toxicity. The IC₅₀ of the AmB-gel for promastigotes was less than 1 µg/mL for the four species examined, i.e., <i>Leishmania infantum</i>, <i>Leishmania tropica</i>, <i>Leishmania major</i>, and <i>Leishmania braziliensis</i>, and less than 2 µg/mL for amastigotes of <i>Leishmania infantum</i> and <i>Leishmania tropica</i>. The AmB-gel caused notable effects on the surface of promastigotes. Computational analysis revealed primarily hydrophobic and van der Waals interactions between AmB and Pluronic^® F127 and ergosterol. <b>Conclusions</b>: Based on the drug retention content and IC₅₀ values observed for both parasite stages, the AmB-gel may be a promising candidate for in vivo studies in patients with cutaneous leishmaniasis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Importance of Murine Models in Determining In Vivo Pharmacokinetics, Safety, and Efficacy in Antimalarial Drug Discovery.","authors":"Glory Adebayo, Opeyemi I Ayanda, Matthias Rottmann, Olusola S Ajibaye, Gbolahan Oduselu, Julius Mulindwa, Olayinka O Ajani, Oluwagbemiga Aina, Pascal Mäser, Ezekiel Adebiyi","doi":"10.3390/ph18030424","DOIUrl":"10.3390/ph18030424","url":null,"abstract":"<p><p>New chemical entities are constantly being investigated towards antimalarial drug discovery, and they require animal models for toxicity and efficacy testing. Murine models show physiological similarities to humans and are therefore indispensable in the search for novel antimalarial drugs. They provide a preclinical basis (following in vitro assessments of newly identified lead compounds) for further assessment in the drug development pipeline. Specific mouse strains, non-humanized and humanized, have successfully been infected with rodent <i>Plasmodium</i> species and the human <i>Plasmodium</i> species, respectively. Infected mice provide a platform for the assessment of treatment options being sought. In vivo pharmacokinetic evaluations are necessary when determining the fate of potential antimalarials in addition to the efficacy assessment of these chemical entities. This review describes the role of murine models in the drug development pipeline. It also explains some in vivo pharmacokinetic, safety, and efficacy parameters necessary for making appropriate choices of lead compounds in antimalarial drug discovery. Despite the advantages of murine models in antimalarial drug discovery, certain limitations are also highlighted.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Vatairea</i> Genus as a Potential Therapeutic Agent-A Comprehensive Review of Ethnobotanical, Phytochemical, and Pharmacological Properties.","authors":"Sarah Andrade Toledo, Laryssa Danielle da Silva Reis, Brenda Costa da Conceição, Lucas Villar Pedrosa da Silva Pantoja, Fábio José Coelho de Souza-Junior, Flávia Cristina Santos Garcez, Cristiane Socorro Ferraz Maia, Eneas Andrade Fontes-Junior","doi":"10.3390/ph18030422","DOIUrl":"10.3390/ph18030422","url":null,"abstract":"<p><p>The <i>Vatairea</i> genus (Fabaceae family) is widespread in the Amazon rainforest. Some species of this genus are known for their ethnobotanical significance and biological potential. The present study explores the pharmacological and promising therapeutic activities, ethnobotanical profile, and phytochemical prospection of <i>Vatairea</i> sp., a monophyletic group of flowering plants, which includes economically and culturally important genera due to their diverse uses, including medicinal applications. <i>V. lundellii</i>, <i>V. guianensis</i>, <i>V. erythrocarpa</i>, <i>V. fusca</i>, <i>V. heteroptera</i>, <i>V. paraensis</i>, <i>V. sericea</i>, and <i>V. macrocarpa</i> are included in the <i>Vatairea</i> sp., also recognized for its high wood quality and potential medicinal properties. Studies show significant antibacterial activity in <i>V. guianensis</i> extracts against Gram-positive and Gram-negative bacteria, whereas <i>V. macrocarpa</i> lectin exhibits broad-spectrum antibacterial effects, including modulation of antibiotic resistance. Additionally, <i>V. macrocarpa</i> and <i>V. guianensis</i> have demonstrated antifungal properties, with compounds like Vatacarpan exhibiting potent activity against <i>Candida</i> sp. In vivo studies highlight the neurotoxic effects of <i>V. macrocarpa</i> lectin, suggesting a dual role in the central nervous system. Despite these findings, research on Vatairea's toxicological aspects is limited, with only a few studies on <i>V. macrocarpa</i> and <i>V. guianensis</i> extracts indicating a need for further exploration of this genus' pharmacological and therapeutic potential.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Medication-Related Osteonecrosis of the Jaw Prediction Model Using the FDA Adverse Event Reporting System Database and Machine Learning.","authors":"Shinya Toriumi, Komei Shimokawa, Munehiro Yamamoto, Yoshihiro Uesawa","doi":"10.3390/ph18030423","DOIUrl":"10.3390/ph18030423","url":null,"abstract":"<p><p><b>Background:</b> Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event. Herein, we conducted a quantitative structure-activity relationship analysis using the U.S. Food and Drug Administration Adverse Drug Reaction Database System (FAERS) and machine learning to construct a drug prediction model for MRONJ induction based solely on chemical structure information. <b>Methods:</b> A total of 4815 drugs from FAERS were evaluated, including 70 and 139 MRONJ-positive and MRONJ-negative drugs, respectively, identified based on reporting odds ratios, Fisher's exact tests, and ≥100 total adverse event reports. Then, we calculated 326 chemical structure descriptors for each drug and compared three supervised learning algorithms (random forest, gradient boosting, and artificial neural networks). We also compared the number of chemical structure descriptors (5, 6, 7, 8, 9, 10, 20, and 30 descriptors). <b>Results:</b> We indicated that the MRONJ prediction model using an artificial neural network algorithm and eight descriptors achieved the highest validation receiver operating characteristic curve value of 0.778. Notably, the total polar surface area (ASA_P) was among the top-ranking descriptors, and MRONJ-positive drugs such as bisphosphonates and anticancer drugs showed high values. Our final model demonstrated a balanced accuracy of 0.693 and a specificity of 0.852. <b>Conclusions:</b> In this study, our MRONJ-inducing drug prediction model identified drugs with polar surface area properties as potential causes of MRONJ. This study demonstrates a promising approach for predicting MRONJ risk, which could enhance drug safety assessment and streamline drug screening in clinical and preclinical settings.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Benefits of In Silico Methods: A Promising Alternative in Natural Compound's Drug Discovery and Repurposing for HBV Therapy.","authors":"Samuel Chima Ugbaja, Aganze Gloire-Aimé Mushebenge, Hezekiel Kumalo, Mlungisi Ngcobo, Nceba Gqaleni","doi":"10.3390/ph18030419","DOIUrl":"10.3390/ph18030419","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) is an important global public health issue. The World Health Organization (WHO) 2024 Global Hepatitis Report estimated that the global prevalence of people living with HBV infection is 254 million, with an estimated prevalence incidence of 1.2 million new HBV infections yearly. Previous studies have shown that natural compounds have antiviral inhibition potentials. In silico methods such as molecular docking, virtual screening, pharmacophore modeling, quantitative structure-activity relationship (QSAR), and molecular dynamic simulations have been successfully applied in identifying bioactive compounds with strong binding energies in HBV treatment targets. The COVID-19 pandemic necessitated the importance of repurposing already approved drugs using in silico methods. This study is aimed at unveiling the benefits of in silico techniques as a potential alternative in natural compounds' drug discovery and repurposing for HBV therapy. Relevant articles from PubMed, Google Scholar, and Web of Science were retrieved and analyzed. Furthermore, this study comprehensively reviewed the literature containing identified bioactive compounds with strong inhibition of essential HBV proteins. Notably, hesperidin, quercetin, kaempferol, myricetin, and flavonoids have shown strong binding energies for hepatitis B surface antigen (HBsAg). The investigation reveals that in silico drug discovery methods offer an understanding of the mechanisms of action, reveal previously overlooked viral targets (including PreS1 Domain of HBsAg and cccDNA (Covalently Closed Circular DNA) regulators, and facilitate the creation of specific inhibitors. The integration of in silico, in vitro, and in vivo techniques is essential for the discovery of new drugs for HBV therapy. The insights further highlight the importance of natural compounds and in silico methods as targets in drug discovery for HBV therapy. Moreover, the combination of natural compounds, an in silico approach, and drug repurposing improves the chances of personalized and precision medicine in HBV treatment. Therefore, we recommend drug repurposing strategies that combine in vitro, in vivo, and in silico approaches to facilitate the discovery of effective HBV drugs.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}