Current drug discovery technologies最新文献

{"title":"<i>In silico</i> Evaluation of NO-Sartans against SARS-CoV-2.","authors":"Negar Omidkhah, Farzin Hadizadeh, Razieh Ghodsi, Prashant Kesharwani, Amirhossein Sahebkar","doi":"10.2174/0115701638279362240223070810","DOIUrl":"10.2174/0115701638279362240223070810","url":null,"abstract":"<p><strong>Introduction: </strong>Numerous clinical trials are currently investigating the potential of nitric oxide (NO) as an antiviral agent against coronaviruses, including SARS-CoV-2. Additionally, some researchers have reported positive effects of certain Sartans against SARS-CoV-2.</p><p><strong>Method: </strong>Considering the impact of NO-Sartans on the cardiovascular system, we have compiled information on the general structure, synthesis methods, and biological studies of synthesized NOSartans. <i>In silico</i> evaluation of all NO-Sartans and approved sartans against three key SARS-CoV- -2 targets, namely M^pro (PDB ID: 6LU7), NSP16 (PDB ID: 6WKQ), and ACE-2 (PDB ID: 1R4L), was performed using MOE.</p><p><strong>Results: </strong>Almost all NO-Sartans and approved sartans demonstrated promising results in inhibiting these SARS-CoV-2 targets. Compound 36 (CLC-1280) showed the best docking scores against the three evaluated targets and was further evaluated using molecular dynamics (MD) simulations.</p><p><strong>Conclusion: </strong>Based on our <i>in silico</i> studies, CLC-1280 (a Valsartan dinitrate) has the potential to be considered as an inhibitor of the SARS-CoV-2 virus. However, further <i>in vitro</i> and <i>in vivo</i> evaluations are necessary for the drug development process.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e050324227669"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041134","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":"Finerenone: A Novel Drug Discovery for the Treatment of Chronic Kidney Disease.","authors":"Akshita Rana, Jagdish K Sahu","doi":"10.2174/0115701638283354240103115420","DOIUrl":"10.2174/0115701638283354240103115420","url":null,"abstract":"<p><strong>Background: </strong>The most common cause of chronic kidney disease (CKD) is diabetic nephropathy (DN). Primarilymineralocorticoid receptor antagonists (MRAs) (spironolactone and eplerenone), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were used for the treatment of CKD, but due to the high risk of hyperkalaemia, the combination was infrequently used. Currently after approval by FDA in 2021, finerenone was found to be effective in the treatment of CKD. Finerenone slowdowns the progression of diabetic nephropathy and lessens the cardiovascular morbidity in DN patients.</p><p><strong>Objective: </strong>The main objective of this review article is to provide a comprehensive and insightful overview of the role of finerenone by mainly focusing on its pharmacological properties, toxicity, uses, bioanalytical technique used for determination, and treatment options.</p><p><strong>Materials and method: </strong>Finerenone works by inhibiting the action of the mineralocorticoid receptor. Finerenone is quickly absorbed from the digestive tract after oral treatment and achieves peak plasma concentrations in 1-2 hours.</p><p><strong>Result: </strong>Finerenone is actively metabolized through oxidation, epoxidation substitution, and direct hydroxylation. Elimination of finerenone is done through urine and feces. Determination of finerenone can be done through HPLC-MS and LSC.</p><p><strong>Conclusion: </strong>The present review covers the complete picture of ADME properties, bioanalytical techniques, clinical trials, toxicity, and possible avenues in this arena. Finerenone is effective compared to other mineralocorticoid receptor-like spironolactone and eplerenone, for the treatment of chronic kidney disease.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e290124226291"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577279","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":"Docking of T6361 Analogues as Potential Inhibitors of <i>E.coli</i> MurA Followed by ADME-Toxicity Study.","authors":"Ilham Boulhissa, Hanane Boucherit, Abdelouahab Chikhi, Abderrahmane Bensegueni","doi":"10.2174/0115701638244582231025110143","DOIUrl":"10.2174/0115701638244582231025110143","url":null,"abstract":"<p><strong>Background: </strong>Developing more potent antibacterial agents is one of the most important tasks of scientists in the health field due to the problem of antibiotic resistance. Among the antibiotic targets, we mention MurA (UDP-N-Acetylglucosamine Enolpyruvyl Transferase), which is a key enzyme of peptidoglycan biosynthesis of the bacterial cell wall.</p><p><strong>Objective: </strong>Our objective was to search for new inhibitors of the bacterial enzyme MurA by docking the analogues of its inhibitor T6361, a derivative of 5-sulfonoxy-anthranilic acid.</p><p><strong>Methods: </strong>990 analogues of T6361 were docked in the first binding site of <i>E.coli</i> MurA (open form) using the FlexX program, and the ADME-Toxicity profile of the best ones was evaluated by SwissADME and PreADMET web servers. .</p><p><strong>Results: </strong>Docking results revealed two T6361 analogues to provide better energy scores than T6361, and have similar interactions with the binding site of E.coli MurA namely,3-{[2-(piperidine-1-carbonyl) phenyl]sulfamoyl}benzoic acid and 3-{[2-(pyrrolidine-1 carbonyl)phenyl]sulfamoyl}benzoic acid. Moreover, the two molecules were found to possess good pharmacokinetics and low toxicity.</p><p><strong>Conclusion: </strong>We propose two analogues of T6361 as new potential inhibitors of MurA enzyme. Their good ADME-Toxicity profile qualifies them to reach <i>in vitro</i> and <i>in vivo</i> assays as future lead molecules.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490308","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":"The Evolving Landscape of Pharmaceutical Regulation: Striking a Balance between Innovation and Safety.","authors":"Debanjan Mukherjee, Sarjana Raikwar","doi":"10.2174/0115701638287851240102110705","DOIUrl":"10.2174/0115701638287851240102110705","url":null,"abstract":"","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e100124225448"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418830","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 on the Role of Phytoconstituents Chrysin on the Protective Effect on Liver and Kidney.","authors":"Debika Sarmah, Rupa Sengupta","doi":"10.2174/0115701638242317231018144944","DOIUrl":"10.2174/0115701638242317231018144944","url":null,"abstract":"<p><strong>Background: </strong>The chance of contracting significant diseases increases due to an unhealthy and contemporary lifestyle. Chrysin is a flavonoid of the flavone class in numerous plants, including Passiflora and Pelargonium. Chrysin has long been used to treat a variety of illnesses. Chrysin, an essential flavonoid, has many pharmacological actions, including anticancer, antiviral, anti-inflammatory, anti-arthritic, depressive, hypolipidemic, hepatoprotective, and nephroprotective activity.</p><p><strong>Purpose: </strong>This explorative review was commenced to provide a holistic review of flavonoids confirming that Chrysin has a therapeutic potential on the liver and kidney and reduces the hepatotoxicity and nephrotoxicity induced by diverse toxicants, which can be helpful for the toxicologists, pharmacologists, and chemists to develop new safer pharmaceutical products with chrysin and other toxicants.</p><p><strong>Study design: </strong>The most relevant studies that were well-explained and fit the chosen topic best were picked. The achieved information was analyzed to determine the outcome by screening sources by title, abstract, and whole work. Between themselves, the writers decided on the studies to be considered. The necessary details were systematically organized into titles and subtitles and compressively discussed.</p><p><strong>Method: </strong>The information presented in this review is obtained using targeted searches on several online platforms, including Google Scholar, Scifinder, PubMed, Science Direct, ACS publications, and Wiley Online Library. The works were chosen based on the inclusion criteria agreed upon by all authors.</p><p><strong>Results: </strong>Chrysin is a promising bioactive flavonoid with significant health benefits, and its synthetic replacements are being utilized as pharmaceuticals to treat various diseases. Findings revealed that Chrysin exhibits hepatoprotective actions against several hepatotoxicants like 2,3,7,8 tetrachlorodibenzo- p-dioxin, carbon tetrachloride (CCl₄), cisplatin, and others by lowering the levels of liver toxicity biomarkers and enhancing antioxidant levels. Additionally, chrysin has potential nephroprotective properties against various nephrotoxicants, like Cisplatin, Doxorubicin, Paracetamol, Gentamicin, Streptazosin, and others by dropping kidney toxicity marker levels, reducing oxidative stress, and improving the antioxidant level.</p><p><strong>Conclusion: </strong>According to this revised study, chrysin is a promising phytoconstituent that can be utilized as an alternate treatment for various medications that cause hepatotoxicity and nephrotoxicity. With active chrysin, several dosage forms targeting the liver and kidneys can be formulated.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e251023222716"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430436","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":"Restoring Impaired Neurogenesis and Alleviating Oxidative Stress by Cyanidin against Bisphenol A-induced Neurotoxicity: <i>In Vivo</i> and <i>In Vitro</i> Evidence.","authors":"Swathi Suresh, Chitra Vellapandian","doi":"10.2174/0115701638280481231228064532","DOIUrl":"10.2174/0115701638280481231228064532","url":null,"abstract":"<p><strong>Background: </strong>Bisphenol A (BPA) is a known neurotoxic compound with potentially harmful effects on the nervous system. Cyanidin (CYN) has shown promise as a neuroprotective agent.</p><p><strong>Objective: </strong>The current study aims to determine the efficacy of CYN against BPA-induced neuropathology.</p><p><strong>Methods: </strong><i>In vitro</i> experiments utilized PC12 cells were pre-treated with gradient doses of CYN and further stimulated with 10ng/ml of BPA. DPPH radical scavenging activity, catalase activity, total ROS activity, and nitric oxide radical scavenging activity were done. <i>In vivo</i> assessments employed doublecortin immunohistochemistry of the brain in BPA-exposed Sprague-Dawley rats. Further, <i>In silico</i> molecular docking of CYN with all proteins involved in canonical Wnt signaling was performed using the Autodock v4.2 tool and BIOVIA Discovery Studio Visualizer.</p><p><strong>Results: </strong>IC₅₀ values of CYN and ascorbic acid were determined using dose-response curves, and it was found to be 24.68 ± 0.563 μg/ml and 20.69 ± 1.591μg/ml, respectively. BPA-stimulated cells pre-treated with CYN showed comparable catalase activity with cells pre-treated with ascorbic acid (p = 0.0287). The reactive species production by CYN-treated cells was significantly decreased compared to BPA-stimulated cells (p <0.0001). Moreover, CYN significantly inhibited nitric oxide production compared to BPA stimulated and the control cells (p < 0.0001). <i>In vivo</i> CYN positively affected immature neuron quantity, correlating with dosage. During molecular docking analysis, CYN exhibited a binding affinity > -7 Kcal/mol with all the key proteins associated with the Wnt/β- catenin signaling cascade.</p><p><strong>Conclusion: </strong>Conclusively, our finding suggests that CYN exhibited promise in counteracting BPAinduced oxidative stress, improving compromised neurogenesis in hippocampal and cortical regions, and displaying notable interactions with Wnt signaling proteins. Thereby, CYN could render its neuroprotective potential against BPA-induced neuropathology.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e250124226256"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567720","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}