Current drug discovery technologies最新文献

{"title":"Discovering Active Chemotherapeutic Agents for Sexually Transmitted Diseases to Inhibit Pathogenic HPV-16-E6 Protein.","authors":"Vemula Vani, Manikandan Alagumuthu, Sanjay Prasad, Nikita Paul, Nithya Gajendra, Pooja Narayanaswamy, Pooja Venkataraman","doi":"10.2174/0115701638336294250109052352","DOIUrl":"https://doi.org/10.2174/0115701638336294250109052352","url":null,"abstract":"<p><strong>Background: </strong>One of the most prevalent sexually transmitted diseases (STDs) is infection with the human papillomavirus (HPV). The current treatment methods comprise employing chemotherapeutic medications or doing surgery to remove the developed tumors. A more affordable option for treating HPV-related diseases has emerged with the advent of medication-based therapy. The interaction between E6 protein and E6AP generates a p53 degradation complex in HPV-infected cells, which facilitates carcinogenesis.</p><p><strong>Objective: </strong>The purpose of this work is to use a virtual screening technique to find possible small molecule inhibitors against the HPV16 E6 protein.</p><p><strong>Methods: </strong>Compounds 5, 7, and 10 are three new HPV 16 E6 inhibitors that were created utilizing a fragment-based methodology. The trials subset in the ZINC database was screened virtually using the structural information of these three novel chemicals, yielding 9800 hits. Using the GLIDE module of the Schrodinger software, three virtual screening phases were applied to the molecules that were collected from the database. MD simulations and DFT (Density Function Theory) were also carried out.</p><p><strong>Results: </strong>The findings indicated that when compared to the reference molecule, luteolin, the five-hit compounds (ZINC000034853956, ZINC000001534965, ZINC000095617673, ZINC000005764481, and ZINC000071606215) demonstrated superior glide scores. Important interactions between these compounds and the HPV 16 E6 protein were seen. Using the QikProp tool, the pharmacokinetic characteristics of these hit compounds were examined. The findings demonstrated that the pharmacokinetic characteristics and oral absorption by humans of all five compounds were found to be satisfactory. Except for ZINC000005764481, all five hit compounds were predicted to be toxic; the remaining four displayed drug-like characteristics.</p><p><strong>Conclusion: </strong>To create HPV 16 E6 inhibitors for the treatment of HPV-related disorders, the four hit compounds (ZINC000034853956, ZINC000001534965, ZINC000095617673, and ZINC00007160- 6215) can be employed as lead molecules.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico based Diabetic Wound Healer from Nature: An Update.","authors":"Amit Lather, Pratibha Rathee, Manish Kumar Gautam, Kalicharan Sharma, Tanuj Hooda","doi":"10.2174/0115701638336128250122223221","DOIUrl":"https://doi.org/10.2174/0115701638336128250122223221","url":null,"abstract":"<p><p>Diabetes is a chronic metabolic disease of high levels of glucose in the blood and affecting 536.6 million people in the world between the age group of 20-79 with management spent of 11% of the total worldwide. Wound healing in diabetics is impaired due to many factors like high blood sugar, poor blood circulation, damaged blood vessels, diabetic neuropathy, decreased immune responses etc. The presently used synthetic drugs have high costs, a toxic nature, and are full of adverse effects drawing attention to the need to identify new and successful treatment approaches for diabetic wounds. In silico drug screening methods of drug development made it easy to screen thousands of active constituents against a target specifically responsible for diabetes and wound healing. Thus the current review compiled the naturally available active compounds screened by in silico docking from natural resources and has the potential to treat diabetic wound healing with their specificity and target-based mechanism. This information will be helpful for further screening of non-reported natural compounds having antidiabetic as well as wound healing potential.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tecelra's Approval: A Breakthrough in Synovial Sarcoma Therapy.","authors":"Dinesh Kumar, Rajni Tanwar, Raj Kamal, Debanjan Mukherjee","doi":"10.2174/0115701638357969250131102049","DOIUrl":"https://doi.org/10.2174/0115701638357969250131102049","url":null,"abstract":"","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Development, Applications, and Patents of Artificial Intelligence in Drug Design and Development.","authors":"Prashant Kumar, Alpana Mahor, Roopam Tomar","doi":"10.2174/0115701638364199250123062248","DOIUrl":"https://doi.org/10.2174/0115701638364199250123062248","url":null,"abstract":"<p><p>Drug design and development are crucial areas of study for chemists and pharmaceutical companies. Nevertheless, the significant expenses, lengthy process, inaccurate delivery, and limited effectiveness present obstacles and barriers that affect the development and exploration of new drugs. Moreover, big and complex datasets from clinical trials, genomics, proteomics, and microarray data also disrupt the drug discovery approach. The integration of Artificial Intelligence (AI) into drug design is both timely and crucial due to several pressing challenges in the pharmaceutical industry, including the escalating costs of drug development, high failure rates in clinical trials, and the in-creasing complexity of disease biology. AI offers innovative solutions to address these challenges, promising to improve the efficiency, precision, and success rates of drug discovery and development. Artificial intelligence (AI) and machine learning (ML) technology are crucial tools in the field of drug discovery and development. More precisely, the field has been revolutionized by the utilization of deep learning (DL) techniques and artificial neural networks (ANNs). DL algorithms & ML have been employed in drug design using various approaches such as physiochemical activity, polyphar-macology, drug repositioning, quantitative structure-activity relationship, pharmacophore modeling, drug monitoring and release, toxicity prediction, ligand-based virtual screening, structure-based vir-tual screening, and peptide synthesis. The use of DL and AI in this field is supported by historical evidence. Furthermore, management strategies, curation, and unconventional data mining aided as-sistance in modern modeling algorithms. In summary, the progress made in artificial intelligence and deep learning algorithms offers a promising opportunity for the development and discovery of effec-tive drugs, ultimately leading to significant benefits for humanity. In this review, several tools and algorithmic programs have been discussed which are being used in drug design along with the de-scriptions of the patents that have been granted for the use of AI in this field, which constitutes the main focus of this review and differentiates it fromalready published materials.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Modeling Studies and Synthesis of Isocryptolepine Derivatives as Antimalarial Using Docking, CoMFA, CoMSIA, and HQSAR.","authors":"Shourya Pratap, Abhilasha Mittal, Sambit Kumar Parida","doi":"10.2174/0115701638333384250117165601","DOIUrl":"https://doi.org/10.2174/0115701638333384250117165601","url":null,"abstract":"<p><strong>Background: </strong>Our research highlights the synthesis of newer antimalarial compounds using molecular modeling studies.</p><p><strong>Objective: </strong>The study investigates a series of isocryptolepine derivatives from previous literature, focusing on their biological activities as antimalarial agents.</p><p><strong>Methods: </strong>Computational methods such as molecular docking and QSAR were employed to gain insights into the interaction between the synthesized compounds and the target enzyme PfDHFR-TS.</p><p><strong>Results: </strong>Molecular docking studies helped to identify key binding interactions, supporting the design of more effective compounds. Using CoMFA and CoMSIA, the study explored steric, electrostatic, and hydrogen-bonding fields, providing a quantitative structure-activity relationship (QSAR) for 49 compounds.</p><p><strong>Conclusion: </strong>The CoMFA model yielded strong predictive r² values of 0.971, while the CoMSIA model highlighted the significance of hydrophobic and hydrogen bond interactions. These findings inform the design of novel isocryptolepine derivatives with improved antimalarial activity.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of the Antiviral Activity of Berberine.","authors":"Fatemeh Forouzanfar, Zahra Meshkat","doi":"10.2174/0115701638360834250113111936","DOIUrl":"https://doi.org/10.2174/0115701638360834250113111936","url":null,"abstract":"<p><p>Berberine is an isoquinoline alkaloid with strong pharmacological activity such as analgesic, antioxidant, neuroprotective, antivirus, anti-inflammatory, anti-seizure, anti-obesity, and hypolipidemic effects. Accumulated evidence indicates berberine plays an inhibitory role against infection of numerous viruses, including human immunodeficiency virus, respiratory syncytial virus, hepatitis C virus, human papillomavirus, human cytomegalovirus, and influenza virus. Berberine's antiviral action has shown promise, making it a viable option for synergistically enhancing the inhibitory effect of current antiviral medicines. This review provides an overview of prior berberine antiviral studies to prepare for its potential use as a natural antiviral agent in future research.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Impairment Caused by Statins in Rats Can Be Restored by Thymoquinone.","authors":"Sherif S Hassan, Charity Thomann, Shaimaa Amin, Magdy Youakim, Ehab A A El-Shaarawy, Sara Shawky Ibrahim","doi":"10.2174/0115701638333036250106040617","DOIUrl":"https://doi.org/10.2174/0115701638333036250106040617","url":null,"abstract":"<p><strong>Background: </strong>Atorvastatin (ATO) is an HMG-CoA reductase inhibitor used to lower blood cholesterol, but it causes renal injury in high doses. Thymoquinone (TQ), is a natural antioxidant that has been shown to protect the kidney through its anti-inflammatory, antioxidant, & antiapoptotic, effects.</p><p><strong>Objective: </strong>The current study aimed to investigate whether posttreatment TQ could reverse ATOinduced renal injury, and the possible mechanism of action by which TQ produced such an effect.</p><p><strong>Methods: </strong>Forty adult male rats were divided into 4 groups: (control; TQ-treated; ATO-treated; ATO plus TQ-treated). Blood and kidney tissue samples were tested for kidney functions, oxidative stress and apoptosis markers, and morphometric analyses of the histopathological and ultrastructural evaluations. Statistical analyses were done using JASP, Shapiro-Wilk, and Levene's test. ANOVA and Kruskal-Wallis tests were done to determine differences between groups. The significance level was set at p<.05.</p><p><strong>Results: </strong>The ATO-treated group showed abnormal outcome measures including kidney functions, oxidative stress and apoptotic markers, and morphometric analyses of the histopathological and ultrastructural findings. Post-treatment TQ improved all outcome measures.</p><p><strong>Conclusion: </strong>Posttreatment TQ could reverse oxidative stress-induced renal injury produced by highdose ATO, suggesting a potential clinical application in patients with renal insufficiency with hypercholesterolemia.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptic Ulcer Disease: A Comprehensive Review on Conventional Therapy and Herbal Treatment.","authors":"Vijay Kumar, Vrinda Goel, Sakshi Bajaj, Kalpana Garg, Anurag Bhargava, Ashwani K Dhingra","doi":"10.2174/0115701638332791250109044742","DOIUrl":"https://doi.org/10.2174/0115701638332791250109044742","url":null,"abstract":"<p><p>Still today, peptic ulcer disease (PUD) is a major digestive illness that affects millions of people around the world every year. This study looks at both traditional and herbal ways of treating PUD, focusing on how they work, how well they work, and whether they can work together. Pharmaceuticals like antibiotics, proton pump inhibitors (PPIs), and H2-receptor antagonists are common ways to treat the condition. In more serious cases, surgery may also be an option. The use of medical plants in phytotherapy, an herbal treatment, has shown promise in helping people with PUD deal with their symptoms and speed up the healing of ulcers. Citrus maxima (Pomelo), a plant in the Rutaceae family, may be able to help treat PUD because it has functional and antioxidant properties. In addition, studies on how well different plants treat PUD have shown that they have anti-inflammatory and cytoprotective qualities. Also, the parts of photosynthesis that plants use contain many beneficial substances that might help with the treatment of PUD. This all-around method would deal with many pathogenic pathways at the same time. More study needs to be done to learn more about how herbal therapies can be used to treat PUD and how they can be combined with other common treatments.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of Nanoparticle Based Antimicrobial Drug Repurposing to Efficiently Target Alzheimer's: A Concise Update on Evidence-based Research and Challenges Ahead.","authors":"Biswabhusan Biswal, Bhabani Sankar Satapathy, Abhishek Mishra, Laxmidhar Maharana, Snigdha Pattnaik","doi":"10.2174/0115701638329824241220055621","DOIUrl":"https://doi.org/10.2174/0115701638329824241220055621","url":null,"abstract":"<p><p>Repurposing of drugs through nanocarriers (NCs) based platforms has been a recent trend in drug delivery research. Various routine drugs are now being repurposed to treat challenging neurodegenerative disorders including Alzheimer disease (AD). AD, at present is one of the challenging neurodegenerative disorders characterized by extracellular accumulation of amyloid-β and intracellular accumulations of neurofibrillary tangles. In spite of catchy progress in drug development, effective treatment outcome in AD patients is far-fetched dream. Out of several proposed hypothesis in the development and progression of AD, potential role of microorganisms causing dementia and AD cannot be ruled out. Several recent researches have been documented a clear correlation in between microbial infection and neuronal damage leading to progression of AD. Thus, antimicrobial drugs repurposing has been emerged as alternate, potential, cost-effective strategy to check progression of AD. Further, for efficient delivery of antimicrobial drugs to brain tissue, novel NCs based platforms are the preferred option to bypass blood-brain barrier. Several polymeric and lipid NCs have been extensively studied over the past years to improve antimicrobial drug delivery to brain. The present review encompasses various repurposing strategy of antimicrobial drugs delivered through various NCs to target AD. Evidence-based research outcome compiled from authentic database like Scopus, PubMed, Web of science have been pooled to provide an updated review. Side by side some light has been thrown on the practical problems faced by nanodrug carriers during technology transfer.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of Computer-Aided Drug Design in Modern Pharmaceutical Research.","authors":"Uma Agarwal, Rajiv Kumar Tonk, Swati Paliwal","doi":"10.2174/0115701638361318241230073123","DOIUrl":"https://doi.org/10.2174/0115701638361318241230073123","url":null,"abstract":"<p><strong>Background: </strong>Computer-Aided Drug Design (CADD) approaches are essential in the drug discovery and development process. Both academic institutions and pharmaceutical and biotechnology corporations utilize them to enhance the efficacy of bioactive compounds.</p><p><strong>Objective: </strong>This study aims to entice researchers by investigating the benefits of Computer-Aided Drug and Design (CADD) and its fundamental principles. The main focus is to speed up the drug discovery process, improve accuracy, and reduce the time and financial resources needed, ultimately making a positive impact on public health.</p><p><strong>Method: </strong>A comprehensive literature search was conducted using databases such as PubMed and Scopus, focusing on studies published till 2024. The selection of studies was based on their analysis of the connection between contemporary pharmaceutical research and computer-aided drug design, with a focus on both structure-based and ligand-based drug design strategies can include molecular docking, fragment-based drug discovery, de novo drug design, pharmacophore modelling, Quantitative structure-activity relationship, 3D-QSAR, homology modelling, in silico absorption-distribution- metabolism-excretion-toxicity, and machine learning/deep learning.</p><p><strong>Result: </strong>Computer-Aided Drug Design (CADD) approaches are mathematical tools used to modify and measure certain characteristics of possible drug candidates. These methods are implemented in various applications. These encompass a variety of software products that are accessible to the public and can be purchased for corporate use. The CADD method is used at several stages of the drug development process, including as a foundation for chemical synthesis and biological testing. It provides information for the development of future SAR (Structure-Activity Relationship), resulting in enhanced molecules in terms of their activity and ADME (Absorption, Distribution, Metabolism, and Excretion). CADD techniques are predominantly employed to analyze and assess the affinity of large molecules for specific biomolecules, such as DNA, RNA, proteins, and enzymes, which serve exclusively as receptors. CADD improves the selection of lead compounds by predicting various parameters, including drug-likeness, physicochemical properties, pharmacokinetics, and toxicity. The application of CADD in drug modelling is to tackle challenges such as cost and time constraints. Modern computer-assisted drug discovery necessitates conducting virtual screening and high-throughput screening (HTS).</p><p><strong>Conclusion: </strong>Computer-aided drug design plays a crucial role for academic institutions and leading pharmaceutical companies in the development of drugs that enhance potency with the significance of reducing both time and costs.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}