Current drug discovery technologies最新文献

{"title":"Computational Screening of Novel Nitroimidazole Candidates: Targeting Key Enzymes of Oral Anaerobes for Anti-Parasitic Potential.","authors":"Touhami Lanez, Maroua Lanez, Riad Lanez, Elhafnaoui Lanez, Badia Talbi-Lanez","doi":"10.2174/0115701638326365241029080310","DOIUrl":"10.2174/0115701638326365241029080310","url":null,"abstract":"<p><strong>Background: </strong>The study focuses on evaluating the parasitic potential of novel metronidazole analogs using computational methods. Specifically, it aims to target key enzymes of oral anaerobes, including UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA) of Fusobacterium nucleatum and DNA topoisomerase (Topo) of Prevotella intermedia.</p><p><strong>Objective: </strong>The objective is to assess the pharmacokinetic and toxicity properties of 368 novel nitroimidazole candidates through virtual screening. Additionally, the study aims to determine the binding affinity of the most promising candidates with the target proteins through molecular docking analyses.</p><p><strong>Methods: </strong>A combinatorial library of nitroimidazole candidates was constructed, and virtual screening was performed. Molecular docking analyses were conducted to evaluate the binding affinity of selected compounds with MurA and Topo. Further investigation involved molecular dynamic simulation to assess the stability of the compounds within the active sites of MurA and Topo.</p><p><strong>Results: </strong>All selected compounds exhibited activity against both MurA and Topo. Among them, Mnz11, Mnz12, and Mnz15 demonstrated the lowest binding free energies and IC50 values. Molecular dynamic simulation indicated that these three compounds remained stable within the active sites of MurA and Topo, with RMSD values consistently below 2Å. Additionally, the antibacterial potential of the most potent compound, Mnz15, was evaluated against a series of oral microbes.</p><p><strong>Conclusion: </strong>The study concludes that the newly identified nitroimidazole candidates show promise as anti-parasitic agents, based on their activity against key enzymes of oral anaerobes and their pharmacokinetic properties evaluated through computational methods.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590774","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":"Preliminary Characterization of the Vasorelaxant Effect of Thymus atlanticus (Ball) Roussine Using Optical Methods.","authors":"Hamza Elbouny, Nabil Bouchebchoub, Brahim Ouahzizi, Rania Hajjami, Younes Filali-Zegzouti, Mohamed Yassine Amarouch, Chakib Alem","doi":"10.2174/0115701638309612240726060844","DOIUrl":"https://doi.org/10.2174/0115701638309612240726060844","url":null,"abstract":"<p><strong>Background: </strong>Thymus atlanticus (Ball) Roussine is a Moroccan endemic thyme species that is traditionally used as an aromatic and medicinal plant. Several studies have demonstrated its pharmacological significance and therapeutic value.</p><p><strong>Objective: </strong>The current study aimed to assess the vasorelaxant effect of the aqueous extract of this species.</p><p><strong>Methods: </strong>The contractility of isolated rat aortas was investigated using the multi-well organ bath technique. This method was adapted and validated in our experimental conditions using epinephrine and hydralazine as vasoconstrictive and vasodilator agents, respectively. The application of 10 μM epinephrine induced a clear vasoconstriction of the aorta rings (Lumen reduction = 31.8±0.4%). However, hydralazine induced a dose-dependent relaxation with an EC50 value of 6.1±1.2 mM. For the aqueous extract of T. atlanticus, the aortic rings were precontracted with epinephrine, and then increasing concentrations (0.125-1 mg/mL) of this extract were added cumulatively.</p><p><strong>Results: </strong>The results have indicated T. atlanticus extract to have a significant vasodilatory effect in a dose-dependent manner (EC50 = 0.52±0.03 mg/mL).</p><p><strong>Conclusion: </strong>The findings provide preliminary evidence of the vasorelaxant effect of the aqueous extract of T. atlanticus using a low-cost optical approach. However, the cellular and molecular mechanisms underlying this effect have yet to be revealed.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585213","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":"AI in Clinical Trials and Drug Development: Challenges and Potential Advancements.","authors":"Divyanshi Gupta, Pranay Wal, Ankita Wal, Sribhavani K R, Mudit Kumar, Krishna Chandra Panda, Mukesh Chandra Sharma","doi":"10.2174/0115701638314252241016165345","DOIUrl":"https://doi.org/10.2174/0115701638314252241016165345","url":null,"abstract":"<p><p>Artificial intelligence (AI) is one of the fastest-growing fields in various industries, including engineering, architecture, medical and clinical research, aerospace, and others. AI, which is a combination of machine learning (ML), deep learning (DL), and human intelligence (HI), is revolutionizing drug discovery and development by making it more cost-effective and efficient. It is also being used in fields such as medicinal chemistry, molecular and cell biology, pharmacology, pharmacokinetics, formulation development, and toxicology. AI plays a crucial role in clinical testing by enhancing patient stratification, patient sample evaluation, and trial design, assisting in the identification of biomarkers, determining efficacy criteria, dose selection, trial length, and target patient population selection. The primary objective of this study is to emphasize the importance of AI in clinical trials and drug development, while also exploring the existing challenges and potential advancements in AI within the healthcare industry. A comprehensive literature review was conducted, covering the period from 1998 to 2023. The Science Direct, PubMed, and Google Scholar databases were searched for relevant information. A variety of publications, including Research Gate, Nature, MDPI, and Springer Link, provided pertinent data. This study aimed to gain a deeper understanding of the use of AI in clinical research and drug development, as well as its potential and limitations. We also discuss the benefits and main data limitations of the traditional trial and drug development approach. AI approaches are currently being used to overcome research obstacles and eliminate conceptual or methodological limitations. After discussing possible obstacles and coping mechanisms, we provide several recommendations to help individuals understand the challenges and difficulties associated with clinical research and drug development. It is essential for pharmaceutical companies to have a cutting-edge AI strategy if AI is to become a routine tool for clinical research and drug development.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549642","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":"An Update on Clinically Evaluated Medicinal Plants for Psoriasis Management.","authors":"Ramin Ansari, Mahkameh Moradi Mehrabadi, Mahnaz Sadat Hosseini, Mehdi Ghahartars, Mohammad Mehdi Zarshenas","doi":"10.2174/0115701638327441241016014503","DOIUrl":"https://doi.org/10.2174/0115701638327441241016014503","url":null,"abstract":"<p><p>Psoriasis is a prevalent inflammatory disease affecting almost 0.5-5 % of the world population. Multiple treatment approaches have been developed to manage psoriasis so far. Although concerns exist in the long-term usage of conventional and biological agents in terms of safety, effectiveness, expensiveness, and tolerability, complementary and alternative medicine (CAM) is a promising point of view for future psoriasis management. In this study, databases including Scopus, PubMed, Google Scholar, and Web of Science were searched for relevant literature on herbal medications clinically evaluated for psoriasis, especially those originating from traditional medicine. About 40 relevant papers were selected by March 2023. Most of the studies were clinical trials on poly-herbal formulations from traditional Chinese medicine (TCM). There are controversial results regarding the efficacy of these herbal formulations in psoriasis mainly due to the variation in the study design. Moreover, the probable protective mechanisms and responsible herbal metabolites of these formulations are summarized. There is a global need for more in-vitro and in-vivo studies based on the standard protocols in terms of the evaluation of the safety and efficacy of topical/ systemic herbal preparations for psoriasis.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549643","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 Vitro Antibacterial Activity of Adiantum capillus Veneris Extraction with Methanol, Chloroform, and Ether Solvents against Methicillin-resistant Staphylococcus aureus.","authors":"Mahdiyeh Ebrahimzadeh, Solmaz Rahbari, Reza Hosseini Doust, Faraz Mojab","doi":"10.2174/0115701638313570241015045118","DOIUrl":"https://doi.org/10.2174/0115701638313570241015045118","url":null,"abstract":"<p><strong>Background: </strong>The increasing problem of multi-drug resistant (MDR) pathogens is a worldwide concern, especially in the pharmaceutical industry. At the same time, medicinal plants have renewed interest because of their wide variety of bioactive phytochemicals, which could be used to develop new antimicrobial drugs. This renewed interest is partly due to the growing resistance to traditional drugs and their associated side effects.</p><p><strong>Methods: </strong>The objective of this study is to assess the antimicrobial properties of the total extract and various fractions of Adiantum capillus veneris against Methicillin-resistant Staphylococcus aureus (MRSA). The aerial parts of Adiantum capillus veneris were subjected to extraction using methanol, chloroform, and ether, and the resulting extracts were tested for their antimicrobial activity against MRSA. Additionally, essential oil was obtained from the aerial parts using a Clevenger apparatus and boiling water. Furthermore, Gas Chromatography-Mass Spectrometry (GC/MS) was utilized to analyze the phytochemicals isolated from the extracts of Adiantum capillus veneris.</p><p><strong>Results: </strong>The essential oil was obtained through distillation and then analyzed using GC/MS. The antimicrobial activity was evaluated using the agar diffusion method.</p><p><strong>Conclusion: </strong>GC/MS analysis revealed that the composition was primarily phytol (59.9%), constituting 99.3% of phyto-constituents. However, both the total extract and the individual fractions exhibited no inhibitory effects against MRSA strains.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549644","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 Role of Benzoic Acid and its Synthetic Derivatives to Alleviate Cancer: An Up-to-Date Review.","authors":"Arvind Kumar, Kamal Yt, Arun K Mishra, Mhaveer Singh, Harpreet Singh, Niranjan Kaushik, Amrita Mishra","doi":"10.2174/0115701638311865240904054111","DOIUrl":"https://doi.org/10.2174/0115701638311865240904054111","url":null,"abstract":"<p><p>Unregulated cell division is one of the main causes of cancer. These cancerous cells negatively impact nearby healthy cells. Cancer can occur anywhere in the body. Normal cell division occurs when cells grow, reproduce, and divide as the body needs. As a normal cascade of cell growth and division, when the cells get damaged, they undergo death, and normal cells develop. However, sometimes, this process is not followed, and abnormal or damaged cells start to grow and multiply several times more than normal. This particular process may form the basis of cancer. There is a research gap in terms of identifying personalized synthetic anticancer therapy, which may be based on individual patient characteristics with an aim to optimize treatment efficacy and minimize adverse effects. While searching for new bioactive compounds, it has been observed that organic molecules with benzoic acid (BA) moiety possess significant anticancer potential. Several works of literature reported the use of BA from natural or synthetic sources to synthesize bioactive chemicals. It has been observed that several natural products also contain BA moiety, and the presence of this moiety is considered responsible for several important biological activities. Therefore, in order to chemically synthesize a wide variety of potent biologically active compounds, benzoic acid as a basic moiety in the form of a scaffold can be employed. Other synthetic compounds with BA scaffolds include furosemide, tetracaine, and bumetanide. The current article aims to focus on past and present work done on BA derivatives and to emphasize the molecular pathways involved in cancer treatment. The future prospects for research in this area are encouraging as researchers are striving to advance synthetic BA derivatives. This could possibly contribute to more efficient treatments and better results for cancer patients.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396227","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 for Solubility Enhancement of Poorly Soluble Drug - A Brief Review.","authors":"Amaresh Prusty, Bikash Ranajn Jena, Vivek Barik, Piyali Khamkat, Bhakti Bhusan Barik","doi":"10.2174/0115701638318659240923074614","DOIUrl":"https://doi.org/10.2174/0115701638318659240923074614","url":null,"abstract":"<p><p>Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396226","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 Profiling and Pharmacokinetic Modelling of Olivetol: Evaluating its Potential as a Therapeutic Agent for Diabetic Wound Healing.","authors":"Nirenjen Shanmugasundaram, Narayanan Jaishankar","doi":"10.2174/0115701638332872240922184903","DOIUrl":"https://doi.org/10.2174/0115701638332872240922184903","url":null,"abstract":"<p><strong>Background: </strong>Diabetic wound healing poses a significant challenge due to the intricate disruptions in cellular and molecular processes induced by hyperglycaemia, leading to delayed or impaired tissue repair. Computational techniques offer a promising avenue for unravelling the complexities of diabetic wound healing by elucidating the molecular mechanisms involved.</p><p><strong>Methodology: </strong>This study utilized in silico molecular docking and dynamics simulations to explore the potential therapeutic effectiveness of olivetol, a phenolic compound, in the context of diabetic wound healing. Furthermore, computational methodologies, encompassing pkCSM, Swiss ADME, OSIRIS® property explorer, PASS online web resource, and MOLINSPIRATION® software, were employed to forecast the pharmacokinetic properties, biological actions, and in vitro analyses, such as MTT and scratch assays, to evaluate the therapeutic effectiveness of olivetol in wound healing.</p><p><strong>Results and discussion: </strong>Our findings have revealed olivetol to be a promising candidate for targeting multiple pathways implicated in diabetic wound healing. Its ability to modulate inflammation, oxidative stress, extracellular matrix remodeling, angiogenesis, and cell signaling suggests a multifaceted approach to promoting effective wound repair. Moreover, olivetol has been found to demonstrate strong binding affinity with key MRSA target proteins, indicating its potential as an antimicrobial agent against MRSA infections in diabetic wounds. The in vitro MTT assay demonstrated cell viability with an IC50 value of 40.80 μM, highlighting its cytotoxicity potential. Additionally, the scratch assay confirmed promising wound healing activity, showcasing its effectiveness in promoting cell migration and closure.</p><p><strong>Conclusion: </strong>Olivetol emerges as a promising candidate for targeted interventions in non-healing diabetic wounds, particularly due to its ability to address prolonged inflammation, a common obstacle in diabetic wound healing.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362574","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":"Bridging the Gap: Quality by Design as a Catalyst for Enhanced Quality Management Systems in Biopharmaceutical Manufacturing.","authors":"Shivang Saxena, Shubhi Saxena, Diksha, Niraj S Patil, Animesh Ranjan, Amandeep Singh","doi":"10.2174/0115701638312326240918093333","DOIUrl":"https://doi.org/10.2174/0115701638312326240918093333","url":null,"abstract":"<p><p>The document emphasizes the importance of addressing key issues in Quality Management Systems (QMS) to stay competitive and provide high-quality goods and services in a dynamic market. It highlights the need to adopt novel quality management techniques for long-term success. The fundamentals of Quality by Design (QbD) are discussed, tracing back to pioneers like Joseph M. Juran and the Six Sigma concept for effective implementation. QbD is described as a systematic approach focusing on risk management, Quality Target Product Profile (QTPP), and Critical Quality Attributes (CQAs) to create products meeting predetermined quality standards. QbD incorporates quality concepts into the development and production processes. Its goal is to guarantee the quality of the product by determining and managing important factors. Manufacturers can be flexible with it while still adhering to strict quality standards. It signifies a change in the industry's paradigm.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335057","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 Comprehensive Investigation: Developing the Pharmaceutical Industry through Artificial Intelligence.","authors":"Deepak Jain, Phool Chandra, Zeeshan Ali, Nishat Fatma, Hafsa Khan","doi":"10.2174/0115701638313233240830132804","DOIUrl":"https://doi.org/10.2174/0115701638313233240830132804","url":null,"abstract":"<p><p>AI's rise has affected many aspects of civilization. Pharmaceutical businesses have been hit hard. This review paper highlights AI's benefits for disease detection, clinical trials, medicine development, and productivity in the pharmaceutical industry. Pharmaceutical companies have built specialized systems to help doctors diagnose and monitor medication remediation. Pharmaceutical businesses are utilizing AI for machine learning to imitate human analytical processes for more accurate and insightful data. AI has many benefits for the pharmaceutical business. Data analysis can address previously insoluble problems due to improved precision. AI boosts productivity, lowers expenses, and enhances tasks. AI insights enhance understanding of user behavior, market performance, and clinical trial success. AI helps identify patients during clinical trials and improves antiviral detection to ensure efficacy, safety, cost-effectiveness, and seamless pharmaceutical procedures. The pharmaceutical industry emphasizes AI in R&D, drug discovery, diagnostics, sickness prevention, epidemic forecasting, remote access, manufacturing, and marketing. Artificial intelligence has transformed medication development and discovery by analyzing vast datasets, discovering complicated patterns, and forecasting efficacy. Pharmaceutical companies like Novartis, AstraZeneca, and Verge Genomics are utilizing AI for drug feature prediction, neurological evaluation, therapy development, pulmonary and hypertension recognition, low-cost medication production, and disease diagnosis.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142110","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}