Current pharmaceutical design最新文献

{"title":"Surgical Excision Margins in Skin Melanomas with Breslow Thickness Greater than 2 Mm: A Systematic Review and Meta-Analysis.","authors":"Lucas Floriano, Rafael Picon, Camila Dagostim, Marcio Chedid","doi":"10.2174/0113816128341363250225095747","DOIUrl":"https://doi.org/10.2174/0113816128341363250225095747","url":null,"abstract":"<p><strong>Objective/background: </strong>This systematic review and meta-analysis aimed to evaluate the efficacy of narrow compared to wide surgical excision margins in the treatment of cutaneous malignant melanomas (MM) with Breslow thickness greater than 2 mm. All prior meta-analyses included studies analyzing patients with a variety of Breslow indexes. There is no prior meta-analysis analyzing the survival of the subgroup of MM patients with MMs > 2 mm in Breslow thickness. Hence, the aim of the present meta-analysis and systematic review was to examine the survival of the subgroup of MM patients with MMs > 2mm in Breslow thickness.</p><p><strong>Methods: </strong>We followed the Cochrane Handbook for Systematic Reviews of Interventions and reported our findings in accordance with PRISMA guidelines. We included randomized controlled trials (RCTs) that compared narrow (1-2 cm) versus wide (3-4 cm) surgical excision margins for cutaneous melanomas thicker than 2 mm. Studies on non-cutaneous melanomas, observational studies, and non-randomized trials were excluded. Ten-year mortality rate and overall survival were the primary outcomes. Our searches were conducted in EMBASE and PUBMED databases.</p><p><strong>Results: </strong>Three RCTs were included, with a total of 2,304 randomized patients. This meta-analysis showed no significant difference in 10-year all-cause mortality between narrow (2 cm) and wide (4 cm) margins (risk difference: 3.3%, 95% CI: -1.7% to 8.2%, p=0.202). Similarly, there was no significant difference in overall survival between narrow (1-2 cm) and wide (3-4 cm) margins (hazard ratio: 1.09, 95% CI: 0.974-1.214, p=0.3). Heterogeneity was low and non-significant.</p><p><strong>Conclusions: </strong>This meta-analysis supports the non-inferiority of narrow (1-2 cm) surgical margins compared to wide (3-4 cm) margins for localized cutaneous melanomas with Breslow thickness greater than 2 mm. These findings suggest that narrow margins could be considered in surgical practice, although a 1 cm margin may be inadequate based on the results of individual studies. Further RCTs focusing on patients with localized MM thicker than 2 mm and taking into account modern adjuvant therapies and sentinel lymph node biopsies are recommended to refine surgical guidelines.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on Novel Therapies for Gastrointestinal Cancers using Translational Platforms.","authors":"Trilochan Satapathy, Shiv Kumar Bhardwaj, Arvind Kumar, Kamal Babu Aditya, Princy Kashyap","doi":"10.2174/0113816128363261250224191453","DOIUrl":"https://doi.org/10.2174/0113816128363261250224191453","url":null,"abstract":"<p><p>Gastrointestinal (GI) cancers, including gastric cancer, are among the most common and deadly cancers worldwide. Patients diagnosed with GI cancer still have a poor prognosis, largely resulting from the late stage of presentation for most of these patients and resistance to conventional therapy. This review covers new therapeutic strategies that apply advances in nanotechnology, immunotherapy, and drug delivery to overcome these challenges. Polymeric and metallic nanoparticles are distinguished for their potential to improve drug stability and solubility, as well as targeting drugs, thus diminishing systemic toxicity. The review centers around the use of immunotherapy in immune checkpoint inhibitors, CAR-T cell therapy, as well as the use of cancer vaccines to re-orient the immune system to be effective against cancer cells. Oncolytic viral therapy and bacteria- based treatments are unique non-conventional approaches that have a potential synergistic impact when used in concomitance with traditional methods. This review presents one of the most promising drug delivery systems: liposomes and micelles that can enhance pharmacokinetics and improve therapeutic results with controlled and site-specific release of anticancer agents. This review critically analyzes the strengths and challenges that include bioavailability, toxicity, and clinical translation, along with strategies to overcome such barriers. The review presents the most salient evidence to date and demonstrates the transformative potential of combining nanotechnology with immunotherapeutic and targeted treatments for managing gastric and other GI cancers. Future research should be focused on optimizing these platforms for clinical applications for the betterment of patient outcomes around the globe.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the PI3K Pathway: Advancements and Achievements in Breast Cancer Therapy.","authors":"Basavana Gowda Hosur Dinesh, Sunil Kumar Bandral, Nandini Markuli Sadashivappa, Srinivas Ganjipete, Damodar Nayak Ammunje, Selvaraj Kunjiappan, Panneerselvam Theivendren, Judy Jays, Parasuraman Pavadai","doi":"10.2174/0113816128357976250122042633","DOIUrl":"https://doi.org/10.2174/0113816128357976250122042633","url":null,"abstract":"<p><p>Breast cancer is a complex disease caused by the aberrant and unchecked proliferation of breast cells, which leads to the development of tumours. In various types of cancer, the Phosphoinositide 3- kinase/Protein kinase B (PKB, also known as Akt (PI3K/Akt) signalling pathway, is essential for controlling cell survival, metastasis, and metabolism. Currently, marketed PI3K inhibitors for treating breast cancer face several issues, including toxicity, resistance, etc. Significant efforts have been made to develop synthetic and repurposed inhibitor drugs to target PI3K, which are now being tested in clinical trials. Developed synthetic PI3K inhibitors have been reported to have better results in clinical trials in the suppression of tumors. This review article mainly focuses on the PI3K pathway at the cellular and molecular level, the development of PI3K inhibitors, and their clinical trials. Biomarkers, marine drugs, synthetic drugs, and repurposed drugs to treat breast cancer are also discussed, followed by mutational changes in PI3K and the resistance mechanism involved in PI3K inhibitors.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical Design and Structure-activity Relationships of Psoralen and Derivatives.","authors":"Yingyue Hu, Yuncan Wang, Wenxiu Qin, Shuo Yu, Siyang Dai, Yuehu Pei, Chang Li, Yihui Yang","doi":"10.2174/0113816128365838250128060007","DOIUrl":"https://doi.org/10.2174/0113816128365838250128060007","url":null,"abstract":"<p><p>Psoralen, the simplest linear furanocoumarin, is derived from many medicinal plants, such as Psoralea corylifolia L., Glehnia littoralis Fr. Schmidt ex Miq., and Peucedanum decursivum (Miq.) Maxim. It has been used for treating osteoporosis and some skin disorders, including vitiligo, psoriasis, and atopic eczema. This review focuses on the pharmaceutical design of psoralen and the structure-activity relationships (SARs) of its derivatives. It also includes the biosynthetic pathways, metabolic characteristics, metabolites, and clinical uses of psoralen, as well as its toxicity/side effects and relevant mechanisms. Psoralen, as a promising drug lead compound, is structurally modified to develop numerous derivatives with remarkable biological activities. SARs discussed herein can guide the design and development of novel psoralen-based derivatives for use in pharmaceuticals and widen their therapeutic potencies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Synthesis of Curcumin Loaded Carbon Dots as a Sustained Drug Delivery for Anticancer Therapy.","authors":"Aniket Saini, Aniket Nandi, Ghanshyam Das Gupta, Ajay Sharma, Kalicharan Sharma","doi":"10.2174/0113816128353103250116112919","DOIUrl":"https://doi.org/10.2174/0113816128353103250116112919","url":null,"abstract":"<p><strong>Aims: </strong>To enhance curcumin's bioavailability with the help of carbon dot and piperine, due to its promising anticancer activity.</p><p><strong>Background: </strong>Cancer is a disease condition, where some cells grow uncontrollably, and if not controlled, they spread to other parts of the body. Concerning anticancer agents, curcumin has anticancer properties along with anti-inflammatory, antimicrobial, and antioxidant. Here in this study, the pharmacokinetic property was improved with the help of Carbon Dot encapsulation.</p><p><strong>Objective: </strong>To improve the bioavailability of curcumin by improved encapsulation efficiency in carbon dots, to achieve a better cytotoxic effect of curcumin.</p><p><strong>Methods: </strong>Bamboo leaves were used for the preparation of CDs and curcumin was loaded in them and the characterization for particle size, morphology, loading capacity, quantum yield, drug release in vitro studies, and in vitro cell viability activity as anticancer activity was done accordingly.</p><p><strong>Results: </strong>Prepared CDs have a smaller particle size (< 10 nm), good loading capacity, stability, and excellent fluorescence activity. Studies on the release of curcumin have shown that a pH-5.5 solution leads to enhanced curcumin release. The CDs-curcumin shows enhanced toxicity against cancerous cells than the curcumin even at lower concentrations (20, 40, 60, 80,100 μM).</p><p><strong>Conclusion: </strong>Curcumin can be delivered by CDs, which have the advantages of increased bioavailability, small size, high loading capacity, improved photoluminescence, and biocompatibility. These characteristics can result in improved anticancer activities even at low concentrations.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Natural Compounds as Potential COVID-19 Main Protease (Mpro) Inhibitors: A Comprehensive Study and In silico Evidence.","authors":"Arti Devi, Vagish Dwibedi, Sahil Jain, Gursharan Kaur, Zaved Ahmed Khan, Sudip Kumar Mandal, Aditya Shiven, Kamal Shah, Hitesh Kumar Dewangan, Santosh Kumar Rath","doi":"10.2174/0113816128344055250220100720","DOIUrl":"https://doi.org/10.2174/0113816128344055250220100720","url":null,"abstract":"<p><p>SARS-CoV-2, the virus responsible for COVID-19, has resulted in a devastating global impact with millions of lives lost. Remdesivir and 2-DG are among the few drugs authorized for emergency use against COVID-19, but concerns about their efficacy and side effects persist. Vaccines have been developed and approved, yet the emergence of viral mutations has raised questions about their effectiveness against new variants. Natural compounds with antiviral properties have shown promise in combating SARS-CoV-2. The review highlights the potential of medicinal plant compounds, particularly in targeting the virus' main protease, a crucial component for viral replication. Natural, plant-derived compounds represent a promising avenue for COVID-19 therapeutics. Further clinical validation is necessary to ascertain their efficacy and safety in treating COVID-19. This underscores the importance of continued research into alternative treatments for combating this global health crisis. This review examines the potential of natural, plant-derived compounds as safe and cost-effective alternatives for combating COVID-19. It summarizes the pathogenesis of SARS-CoV- 2 and the ongoing drug studies and identifies natural compounds with known antiviral properties. Additionally, it explores the potential of medicinal plant compounds in targeting the SARS-CoV-2 main protease through in silico and molecular docking studies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Characterization of Zn(1-x-y)MnxCoyO NPs for Liver Cancer Treatment.","authors":"Nasar Ahmed, Natasha Nazir, Muhammad Asif, M Adnan, M Fakhar-E-Alam, Muhammad Zubair, Khizar Ul Haq, Muhammad Aseer, Muhammad Atif, Safdar Ali","doi":"10.2174/0113816128330548250206101727","DOIUrl":"https://doi.org/10.2174/0113816128330548250206101727","url":null,"abstract":"<p><strong>Introduction: </strong>In this study, pure and cobalt manganese-doped ZnO nanoparticles (Zn(1-x-y)MnxCoyO NPs) at varying concentrations were synthesized through sol-gel method, and zinc acetate dihydrate, manganese nitrate, cobalt acetate, and diethyl amine were used as precursors, with samples finally calcined at 700oC.</p><p><strong>Method: </strong>The hexagonal wurtzite structure of pure and co-doped ZnO NPs was confirmed by X-ray diffraction (XRD). The computed grain sizes of pure and co-doped ZnO NPs, according to Scherrer's formula, were 32 nm, 32.5 nm, 36.3 nm, and 36.5 nm, respectively. SEM was used to observe the morphology of nanoparticles. FTIR spectroscopy was used to examine the chemical make-up and vibrational modes of pure and co-doped ZnO NPs. The bandgaps of pure and doped ZnO were examined using UV-Vis spectroscopy.</p><p><strong>Results: </strong>It was found that the optical bandgap of ZnO was lowered by 3.21 eV by manganese and cobalt doping. Elemental composition analysis was performed by using EDX analysis. Finally, anticancer activity of pure and co-doped ZnO NPs was assessed by employing MTT assay, which indicated that Zn0.8 Mn0.1 Co0.1O NPs showed significant anticancer results against liver cancer (HepG-2) cells as compared to ZnO, Zn0.98 Mn0.01Co0.01O and Zn0.90 Mn0.05 Co0.05O NPs. Moreover, Zn0.8 Mn0.1 Co0.1O NPs showed low toxicity and good biocompatibility comparable to doxorubicin (DOX).</p><p><strong>Conclusion: </strong>Comprehensive experimental findings have demonstrated an authentic way of obtaining feasible in vivo liver cancer therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSAR and Molecular Docking Studies on Uracil-Based Benzoic Acid and Ester Derivatives to Explore Novel Dipeptidyl Peptidase-4 Inhibitors.","authors":"Pradeep Pilania, Prithvi Singh","doi":"10.2174/0113816128331664250206113701","DOIUrl":"https://doi.org/10.2174/0113816128331664250206113701","url":null,"abstract":"<p><strong>Background: </strong>Today, diabetes mellitus (DM) is considered a major global health problem and, especially diabetes mellitus type-2 (T2DM), which accounts for 90-95% of all diabetes cases. Among the novel glucose-lowering agents, dipeptidyl peptidase-4 (DPP-4) inhibitors have been extensively studied in recent years.</p><p><strong>Objectives: </strong>This paper integrates a QSAR study and docking analysis of a series of uracil-based benzoic acid and ester derivatives as novel DPP-4 inhibitors.</p><p><strong>Methods: </strong>The correlation of chemical structure with the biological activity in CP-MLR led to the detection of eleven descriptors from various classes of Dragon descriptors for modeling the activity. The resulting QSAR model has been validated internally and externally using CP-MLR and PLS. Further, the applicability domain analysis revealed the acceptable predictivity of the highest significant model.</p><p><strong>Result: </strong>The best QSAR model displays the r2 Test value of 0.715, Q2 LOO value of 0.797 and Q2 L5O value of 0.809 and this model is used to predict novel compounds with high potency. Further docking study was executed using Autodock 4.2 against DPP-4 protein (PDB ID: 2RGU) that reflects the significant binding potential in newly proposed compounds.</p><p><strong>Conclusion: </strong>From the results, four new congeners have been predicted and validated with good inhibitory activity against DPP-4. Present work reflects that with further optimization of these scaffolds, more selective, potent, and bioavailable DPP-4 inhibitors can be developed for the treatment of T2DM.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell Nanotechnology Applications as Drug Delivery Systems for Neurodegenerative Disorders.","authors":"Md Sadique Hussain, Prasanna Srinivasan Ramalingam, Ajay Singh Bisht","doi":"10.2174/0113816128377684250310073151","DOIUrl":"https://doi.org/10.2174/0113816128377684250310073151","url":null,"abstract":"","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vegetable Oils in Skin Whitening - A Narrative Review.","authors":"Julia Capp Zilles, Marya Alexandrina Vallenot Lemos, Miriam Anders Apel, Irene Clemes Kulkamp-Guerreiro, Aline Rigon Zimmer, Renata Vidor Contri","doi":"10.2174/0113816128361413250107114203","DOIUrl":"https://doi.org/10.2174/0113816128361413250107114203","url":null,"abstract":"<p><p>Plants are a source of a variety of compounds, such as vegetable oils, which are rich in fatty acids and possess skin-whitening properties. Considering the hyperpigmentation treatment challenges (lack of efficacy or aggressiveness), the constant search for new whitening substances is necessary. Given vegetable oils' potential and application in dermatological and cosmetic products, we reviewed the scientific literature on vegetable oils with skin depigmenting activity. It was observed that a variety of species (Adansonia digitata, Arctium lappa, Argania spinosa, Astrocaryum vulgare, Bertholletia excelsa, Borago officinalis, Camellia oleifera, Cucurbita moschata, Euterpe oleraceae, Hevea brasiliensis, Moringa oleifera, Nicotiana tabacum, Oenocarpus bataua, Oenothera biennis, Panax ginseng, Passiflora edulis, Pentaclethra macroloba, Perilla frutescens, Sapindus mukorossi, Taiwanese species Taichung selective No. 4 (TCS4) (Adlay bran), Torreya grandis) were evaluated in vitro regarding their skin whitening properties. All the studies demonstrated that the oils have skin whitening properties and that the oils' activity is related to their composition. The harvesting period, as well as the extraction method, impact on the oils' properties, hence in their activity. The use of vegetable oils can have advantages over an isolated compound as their components can have synergistic or adding effects. When conducting skin whitening experiments, it is recommended to employ multiple assays because vegetable oils can influence skin whitening through various mechanisms. Furthermore, more clinical trials should be encouraged, considering the potential of vegetable oils as skin-lightening ingredients. More innovative and effective formulations can be obtained using vegetable oils for skin whitening purposes.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}