Current drug discovery technologies最新文献

{"title":"Assessment of the <i>In Vivo</i> Reprotoxicity of Isotretinoin in Sprague-Dawley Male Rat.","authors":"Ahmad Khalil, Mai Daradkeh, Amneh Alrabie, Hasan Abo Siam","doi":"10.2174/1570163820666230816155855","DOIUrl":"10.2174/1570163820666230816155855","url":null,"abstract":"<p><strong>Background: </strong>Isotretinoin (ISO) belongs to a family of drugs called retinoids. It is the most effective drug prescribed by dermatologists for the treatment of the inflammatory disease, acne vulgaris. A significant barrier to the use of ISO has worries regarding its adverse effect profile. Despite the well-recognized reproductive toxicity and teratogenicity in females, there is no warning related to the use by male patients in the medication prospectus. Current data on the effects on human male fertility is contradictory and inconclusive.</p><p><strong>Objectives: </strong>This study was undertaken to investigate the potential effects of ISO oral doses in the Sprague-Dawley male rat germ cells using the sperm morphology assay. Also, the serum levels of the follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were measured.</p><p><strong>Methods: </strong>The rat groups were given varying ISO doses via gastric gavage for seven consecutive days. The epididymis sperm specimens were microscopically examined for the following reproductive toxicity parameters: sperm concentration, examined viability, motility, and morphology. The serum FSH, LH, and testosterone levels were measured by using the corresponding enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed statistically by one-way analysis of variance (ANOVA) followed by the Tukey test at P ≤ 0.05 significance level.</p><p><strong>Results: </strong>The results indicated that the drug did not significantly increase the sex hormone levels but notably affected both the sperm quantity and quality.</p><p><strong>Conclusion: </strong>These observations suggest that ISO was reprotoxic, and future therapies should be further reassessed.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e160823219865"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005494","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":"QSAR Studies and Scaffold Optimization of Predicted Novel ACC 2 Inhibitors to Treat Metabolic Syndrome.","authors":"Kirtika Madan, Sarvesh Paliwal, Swapnil Sharma, Seema Kesar, Neha Chauhan, Mansi Madan","doi":"10.2174/1570163820666230901144003","DOIUrl":"10.2174/1570163820666230901144003","url":null,"abstract":"<p><strong>Background: </strong>Metabolic syndrome is one of the major non-communicable global health hazards of the modern world owing to its amplifying prevalence. Acetyl coenzyme-A carboxylase 2 (ACC 2) is one of the most crucial enzymes involved in the manifestation of this disease because of its regulatory role in fatty acid metabolism.</p><p><strong>Objective: </strong>To find novel potent ACC 2 inhibitors as therapeutic potential leads for combating metabolic syndrome.</p><p><strong>Methods: </strong>In the present study, a two-dimensional quantitative structure-activity relationship (2D QSAR) approach was executed on biologically relevant thiazolyl phenyl ether derivatives as ACC 2 inhibitors for structural optimization. The physiochemical descriptors were calculated and thus a correlation was derived between the observed and predicted activity by the regression equation. The significant descriptors i.e. log P (Whole Molecule) and Number of H-bond Donors (Substituent 1) obtained under study were considered for the design of new compounds and their predicted biological activity was calculated from the regression equation of the developed model. The compounds were further validated by docking studies with the prepared ACC 2 receptor.</p><p><strong>Results: </strong>The most promising predicted leads with the absence of an H-bond donor group at the substituted phenyl ether moiety yet increased overall lipophilicity exhibited excellent amino acid binding affinity with the receptor and showed predicted inhibitory activity of 0.0025 μM and 0.0027 μM. The newly designed compounds were checked for their novelty. Lipinski's rule of five was applied to check their druggability and no violation of this rule was observed.</p><p><strong>Conclusion: </strong>The compounds designed in the present study have tremendous potential to yield orally active ACC 2 inhibitors to treat metabolic syndrome.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e010923220643"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181932","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, Synthesis and Evaluation of 4-hydroxy-1-phenyl-2(1H)-quinolone Derivatives as Anticancer Agents.","authors":"Chaitali Prabhu Tendulkar, Prachita Gauns Dessai, Shivlingrao Mamle Desai, Amrita Kadam","doi":"10.2174/1570163820666230719110932","DOIUrl":"10.2174/1570163820666230719110932","url":null,"abstract":"<p><strong>Background: </strong>The estimated number of cancer cases in India for the year 2022 was found to be 14,61,427. The development of chemotherapeutic agents has reduced the mortality rate, however, they have high toxicity which is a disadvantage. Many researchers have found out that quinolin-2- one possesses anticancer activity, with this background we thought of synthesizing the quinolin-2-one derivatives.</p><p><strong>Objective: </strong>This study aimed to carry out docking, synthesis, characterization, and evaluation of 2-(2- (4-Hydroxy-2-oxoquinolin-1(2H)-yl)phenyl/ substituted phenyl)-3-(phenylamino) thiazolidon-4-one derivatives (IVa-g) as an anticancer agent.</p><p><strong>Method: </strong>Diphenylamine and malonic acid treated with phosphoryl chloride gave compound I, which on formylation afforded compound II, which on reaction with various substituted aromatic phenylhydrazine derivatives gave compounds IIIa-g, which on further reaction with thioglycolic acid and anhydrous zinc chloride yielded the compounds IVa-g.</p><p><strong>Result: </strong>Among all the synthesized novel derivatives, compounds IV a-d showed 50% lysis in the IC₅₀ range of 25-50μg for the A549 cell line, and compounds IVa, and IVb showed 50% lysis in the IC₅₀ range of 25-50μg for the MDA-MB cell line. The compound, 3-((4-fluorophenyl)amino)-2-(2-(4- hydroxy-2-oxoquinolin-1(2H)-yl)phenyl)thiazolidin-4-one (IVg) was found to be the most active against both the cell line, A549 and MDA-MB with IC₅₀ value of 0.0298μmol and 0.0338μmol respectively. The docking results revealed that the synthesized compounds exhibited well-conserved hydrogen bonding with one or more amino acid residues in the active pocket of EGFR tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib (PDB ID:1M17). Compound IVg showed the highest MolDock score of -137.813 compared to the standard drug Imatinib having a MolDock score of -119.354.</p><p><strong>Conclusion: </strong>Compound IVg showed the highest MolDock score and was also found to be most potent against both the cell line, A549, and MDA-MB.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e190723218893"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214122","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 Biogenetic Synthesis of Metallic Nanoparticles and the Role they Play in the Anti-inflammatory Drug Treatment.","authors":"Meena Kurup, Mohan Kumar, Sambathkumar Ramanathan, Margret Chandira Rajappa","doi":"10.2174/1570163820666230718123544","DOIUrl":"10.2174/1570163820666230718123544","url":null,"abstract":"<p><strong>Background: </strong>Nanoscience and nanotechnology have resulted in the continuous development of new nanomaterials with remarkable properties that make them appealing for pharmaceutical applications. The biocompatibility of metallic nanoparticles is of increasing interest for research scientists currently working towards developing novel nano-based medicines, industrial chemicals, and antigens. There is also a particular interest in using them to counter mutations that up-regulate inflammation enhancers to produce a range of inflammation-related pathologies.</p><p><strong>Aim: </strong>The following review discusses the anti-inflammatory mechanisms of metallic bioconjugated (silver, gold, zinc oxide, titanium dioxide, and selenium) nanoparticles. The current study focuses on nanoparticle manufacturing technologies and the inflammatory response.</p><p><strong>Methodology: </strong>A thorough search was conducted in several databases, including Scopus, Embase, Cochrane, and PubMed. The search terms used included: Alzheimer's disease, mechanism of action, neuroinflammation, the reaction of Mast cells to stress and neuroinflammation. The study included all publications published in English.</p><p><strong>Results: </strong>Green-synthesised nanoparticles can suppress the NF-B and cyclooxygenase-2 pathways, preventing the production of proinflammatory cytokines and ROS scavenging mechanisms. Metallic nanoparticles with anti-inflammatory properties, such as stability and specific targeting, have been briefly discussed.</p><p><strong>Conclusion: </strong>The current research focuses on metallic nanoparticles employed as anti-inflammatory medication molecules, although nanoparticles have applications in various areas (medicine, chemical engineering, and agriculture). Nanoparticles have a large surface-to-volume ratio, which can help them to penetrate cell membranes, and because of their solid ligand-binding capabilities, nanoparticles have been used in the medical treatment of inflammatory pathologies.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e180723218848"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10190067","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 of Brassicaceae Derivatives for Inhibiting\u0000Lipoxygenases: A Promising Therapeutic Strategy","authors":"W. Soufi, H. Allali, F. B. Hacene, S. Ghalem","doi":"10.2174/0115701638269042231122064738","DOIUrl":"https://doi.org/10.2174/0115701638269042231122064738","url":null,"abstract":"\u0000\u0000Inflammation plays a crucial role in the body's defense mechanisms, but\u0000uncontrolled inflammation can lead to chronic and pathological conditions. This study aimed to\u0000identify natural compounds as potential replacements for the synthetic drug Zileuton, known for its\u0000side effects.\u0000\u0000\u0000\u0000Utilizing the MOE and Molegro modeling methods, several molecules were evaluated, and\u0000three compounds, namely 1-Isothiocyanatopent-4-en-2-ol, 7-Isothiocyanatohept-1-ene, and 5-\u0000(Isothiocyanatomethyl)-1,2,3-trimethoxybenzene, exhibited superior inhibitory properties. These\u0000compounds consistently demonstrated low energy values, indicating high inhibition potency. Notably, 5-(Isothiocyanatomethyl)-1,2,3-trimethoxybenzene emerged as the most promising candidate\u0000among all tested compounds.\u0000\u0000\u0000\u0000These findings provide valuable insights for the development of alternative anti-inflammatory agents. Further research is required to assess the efficacy and safety profiles of these compounds\u0000in clinical settings.\u0000\u0000\u0000\u0000This study represents a significant advancement in the search for innovative therapeutic strategies to manage inflammation-related disorders.\u0000","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139002713","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":"Acknowledgements to Reviewers","authors":"","doi":"10.2174/157016382006231009170813","DOIUrl":"https://doi.org/10.2174/157016382006231009170813","url":null,"abstract":"","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"69 34","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135061597","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":"Virtual Screening, Docking, and Designing of New VEGF Inhibitors as Anti-cancer Agents","authors":"Shivkant Patel, Vinay Ranjan Singh, Ashok Kumar Suman, Surabhi jain, Ashim Kumar Sen","doi":"10.2174/0115701638255384230920040154","DOIUrl":"https://doi.org/10.2174/0115701638255384230920040154","url":null,"abstract":"Background: VEGFR-2 tyrosine kinase inhibitors are receiving a lot of attention as prospective anticancer medications in the current drug discovery process. Objective: This work aims to explore the PubChem library for novel VEGFR-2 kinase inhibitors. 1H-Indazole-containing drug AXITINIB, or AG-013736 (FDA approved), is chosen as a rational molecule for drug design. This scaffold proved its efficiency in treating cancer and other diseases as well. Methods: The present study used the virtual screening of the database, protein preparation, grid creation, and molecular docking analyses. Results: The protein was validated on different parameters like the Ramachandran plot, the ERRAT score, and the ProSA score. The Ramachandran plot revealed that 92.1% of the amino acid residues were located in the most favorable region; this was complemented by an ERRAT score (overall quality factor) of 96.24 percent and a ProSA (Z score) of -9.24 percent. The Lipinski rule of five was used as an additional filter for screening molecules. The docking results showed values of binding affinity between -14.08 and -12.34 kcal/mol. The molecule C1 showed the highest docking value of -14.08 Kcal/mol with the maximum number of strong H-bonds by -NH of pyridine to amino acid Cys104 (4.22Å), -NH of indazole to Glu108 (4.72), and Glu70 to bridge H of -NH. These interactions are similar to Axitinib docking interactions like Glu70, Cys104, and Glu102. The docking studies revealed that pi-alkyl bonds are formed with unsubstituted pyridine, whereas important H-bonds are observed with different substitutions around -NH. Based on potential findings, we designed new molecules, and molecular docking studies were performed on the same protein along with ADMET studies. The designed molecules (M1–M4) also showed comparable docking results similar to Axitinib, along with a synthetic accessibility score of less than 4.5. Conclusion: The docking method employed in this work opens up new possibilities for the design and synthesis of novel compounds that can act as VEGFR-2 tyrosine kinase inhibitors and treat cancer.","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"79 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136361065","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":"Liquisolid Technique: A Novel Technique with Remarkable Applications in Pharmaceutics","authors":"Sahibpreet Singh, Jyoti Singh Singh, Disha Arora","doi":"10.2174/0115701638258285230921025512","DOIUrl":"https://doi.org/10.2174/0115701638258285230921025512","url":null,"abstract":"Abstract: Recently, it has been observed that newly developed drugs are lipophilic and have low aqueous solubility issues, which results in a lower dissolution rate and bioavailability of the drugs. To overcome these issues, the liquisolid technique, an innovative and advanced approach, comes into play. This technique involves the conversion of the drug into liquid form by dissolving it in non-volatile solvent and then converting the liquid medication into dry, free-flowing, and compressible form by the addition of carrier and coating material. It offers advantages like low cost of production, easy method of preparation, and compactable with thermo labile and hygroscopic drugs. It has been widely applied for BCS II drugs to enhance dissolution profile. Improving bioavailability, providing sustained release, minimizing pH influence on drug dissolution, and improving drug photostability are some of the other promising applications of this technology. This review article presents an overview of the liquisolid technique and its applications in formulation development.","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"262 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136360132","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":"Drug Repositioning: A Monetary Stratagem to Discover a New Application of Drugs","authors":"Seema Rohilla, Ankur Rohilla","doi":"10.2174/0115701638253929230922115127","DOIUrl":"https://doi.org/10.2174/0115701638253929230922115127","url":null,"abstract":"Abstract: Drug repurposing, also referred to as drug repositioning or drug reprofiling, is a scientific approach to the detection of any new application for an already approved or investigational drug. It is a useful policy for the invention and development of new pharmacological or therapeutic applications of different drugs. The strategy has been known to offer numerous advantages over developing a completely novel drug for certain problems. Drug repurposing has numerous methodologies that can be categorized as target-oriented, drug-oriented, and problem-oriented. The choice of the methodology of drug repurposing relies on the accessible information about the drug molecule and like pharmacokinetic, pharmacological, physicochemical, and toxicological profile of the drug. In addition, molecular docking studies and other computer-aided methods have been known to show application in drug repurposing. The variation in dosage for original target diseases and novel diseases presents a challenge for researchers of drug repurposing in present times. The present review critically discusses the drugs repurposed for cancer, covid-19, Alzheimer’s, and other diseases, strategies, and challenges of drug repurposing. Moreover, regulatory perspectives related to different countries like the United States (US), Europe, and India have been delineated in the present review.","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136360133","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":"WITHDRAWN: The Sub-chronic Administration of Echium Oil Attenuates the Seizure Threshold and Improves Antioxidant Activity in Pentylenetetrazol- induced Seizure Model of Mice","authors":"Hakimeh Gavzan,&nbsp;Atefeh Araghi,&nbsp;Ramazan Behzadi","doi":"10.2174/1570163820666230418114512","DOIUrl":"https://doi.org/10.2174/1570163820666230418114512","url":null,"abstract":"<p><p>The article has been withdrawn at the request of the Corresponding author.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously\u0000submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere\u0000must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting\u0000the article for publication the authors agree that the publishers have the legal right to take appropriate action against the\u0000authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright\u0000of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522386","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}