Drug Design, Development and Therapy最新文献

{"title":"Updating the Pharmacological Effects of α-Mangostin Compound and Unraveling Its Mechanism of Action: A Computational Study Review.","authors":"Cecep Suhandi, Gofarana Wilar, Angga Cipta Narsa, Ahmed Fouad Abdelwahab Mohammed, Ali El-Rayyes, Muchtaridi Muchtaridi, Shaharum Shamsuddin, Sabreena Safuan, Nasrul Wathoni","doi":"10.2147/DDDT.S478388","DOIUrl":"10.2147/DDDT.S478388","url":null,"abstract":"<p><p>α-Mangostin, initially identified in 1855, is a xanthone derivative compound predominantly located in the pericarp of the mangosteen fruit (<i>Garcinia mangostana</i> L). This compound is known for its beneficial properties as an antioxidant and anti-inflammatory agent, still holding promise for potential benefits in other related pathologies. In the investigative process, computational studies have proven highly valuable in providing evidence and initial screening before progressing to preclinical and clinical studies. This review aims to present the pharmacological findings and mechanisms of action of α-mangostin based on computational studies. The compilation of this review is founded on the analysis of relevant articles obtained from PubMed, Scopus, and ScienceDirect databases. The study commences with an elucidation of the physicochemical characteristics, drug-likeness, pharmacokinetics, and toxicity profile of α-mangostin, which demonstrates that α-mangostin complies with the Lipinski's Rule of Five, exhibits favorable profiles of absorption, distribution, metabolism, and excretion, and presents low toxicity. Subsequent investigations have revealed that computational studies employing various software tools including ArgusLab, AutoDock, AutoDock Vina, Glide, HEX, and MOE, have been pivotal to comprehend the pharmacology of α-mangostin. Beyond its well established roles as an antioxidant and anti-inflammatory agent, α-mangostin is now recognized for its pharmacological effects in Alzheimer's disease, diabetes, cancer, chronic kidney disease, chronic periodontitis, infectious diseases, and rheumatoid arthritis. Moreover, α-mangostin is projected to have applications in pain management and as a potent mosquito larvicide. All of these findings are based on the attainment of adequate binding affinity to specific target receptors associated with each respective pathological condition. Consequently, it is anticipated that these findings will serve as a foundation for future scientific endeavours, encompassing both in vitro and in vivo studies, as well as clinical investigations, to better understand the pharmacological effects of α-mangostin.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4723-4748"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Network Pharmacology and Metabolomics to Reveal the Immunomodulatory Mechanism of Ethnomedicine <i>Rodgersia sambucifolia</i> Hemsl.","authors":"Jiayue Zhou, Yingxiang Wu, Zhiyan Lu, Yan Wang","doi":"10.2147/DDDT.S479341","DOIUrl":"10.2147/DDDT.S479341","url":null,"abstract":"<p><strong>Purpose: </strong><i>Rodgersia sambucifolia</i> Hemsl (also known as <b><i>Yantuo</i></b> ) is a traditional Chinese medicine commonly utilized as a medicinal herb with its rhizomes, mainly used to regulate the immune function of the human body. However, relatively few studies have investigated its active components and potential mechanisms of action in vivo.</p><p><strong>Methods: </strong>First, the chemical composition in vitro was identified and analyzed using the UPLC-Q-TOF MS/MS technique. Cyclophosphamide (CTX) was then administered intraperitoneally to rats to establish an immunosuppression model. Physiological and biochemical parameters, organ indices, and histopathological findings were evaluated for efficacy. Subsequently, potential biomarkers in rat serum were identified using multivariate statistical analysis and enriched and topologized using online platforms such as MetaboAnalyst and KEGG to reveal the critical metabolic pathways and their roles in the immunomodulatory network. Finally, the integrated analysis of components in vivo and in vitro, along with metabolic pathways, was performed using network pharmacology and molecular docking technology to elucidate the mechanisms of their roles in organismal immunity.</p><p><strong>Results: </strong>A total of 28 chemical components in vitro were identified, while pharmacodynamic experiments confirmed the immunomodulatory effects of <b><i>Yantuo</i></b> , especially in the high-dose administration group. Metabolomics analysis showed that 37 potential immune-related biomarkers were identified in positive and negative ion modes, involving 16 metabolic pathways such as arginine biosynthesis, pyrimidine metabolism, and riboflavin metabolism. The results of network pharmacology and molecular docking indicated that <b><i>Yantuo</i></b> may affect 7-O-galloyl-catechin, Cynaroside, Quercetin-7-O-beta-D-glucopyranoside, and 1.6-bis-O-galloyl-beta-D-glucose through interactions with the immune system, with significant pathways of action including galactose metabolism, glycolysis/gluconeogenesis, pyrimidine metabolism, and riboflavin metabolism.</p><p><strong>Conclusion: </strong>In our experiments, we confirmed the organismal modulatory effect of <b><i>Yantuo</i></b> on immunocompromised rats, clarified the key components, target proteins, and pathways of its possible action, and provided possibilities for follow-up studies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4749-4778"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Dexmedetomidine-Esketamine Combination Premedication versus Monotherapy for Reducing Emergence Delirium and Postoperative Behavioral Changes in Pediatric Tonsillectomy and/or Adenoidectomy: A Randomized Controlled Trial.","authors":"Yanling Liao, Siyu Xie, Yifen Zhuo, Sisi Chen, Yuxin Luo, Ying Wei, Yusheng Yao","doi":"10.2147/DDDT.S488706","DOIUrl":"10.2147/DDDT.S488706","url":null,"abstract":"<p><strong>Purpose: </strong>Emergence delirium and postoperative negative behavioral changes (PNBC) are common complications in pediatric anesthesia. This study evaluated whether intranasal premedication combining dexmedetomidine and esketamine more effectively reduces these complications compared to either drug alone in children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia.</p><p><strong>Patients and methods: </strong>This randomized, double-blind trial involved 198 children aged 2-5 years undergoing tonsillectomy and/or adenoidectomy. Participants received intranasal premedication with either dexmedetomidine (2 μg/kg), esketamine (1 mg/kg), or their combination (dexmedetomidine 1 μg/kg plus esketamine 0.5 mg/kg). The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥ 10. Secondary outcomes included the incidence of PNBC, sedation depth, easiness of separation from parents, acceptance of the mask for induction, emergence time, postoperative pain score, parental satisfaction, and adverse events.</p><p><strong>Results: </strong>The combination premedication significantly reduced emergence delirium incidence (9.4%) compared to esketamine alone (38.1%; relative risk [RR] 0.25, 95% confidence interval [CI] 0.11-0.57, p < 0.001), but not compared to dexmedetomidine alone (17.2%; RR 0.55, 95% CI 0.21-1.39, p = 0.193). PNBC incidence at day 7 was lower with the combination (28.1%) versus dexmedetomidine (48.4%; RR 0.58, 95% CI 0.36-0.93, p = 0.018), but not significantly different from esketamine alone (20.6%; RR 1.38, 95% CI 0.74-2.58, p = 0.326). The combination also provided significantly superior sedation, improved ease of separation from parents, better acceptance of the mask for induction, shorter emergence time, and higher parental satisfaction than both monotherapies.</p><p><strong>Conclusion: </strong>In children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia, intranasal dexmedetomidine-esketamine premedication more effectively reduces emergence delirium compared to esketamine alone and PNBC compared to dexmedetomidine alone. This combination also improves sedation, shortens emergence times, and enhances parental satisfaction compared to monotherapy without significant adverse effects.</p><p><strong>Trial registration: </strong>The Chinese Clinical Trial Registry, ChiCTR2300076709.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4693-4703"},"PeriodicalIF":4.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apigenin Attenuates Transverse Aortic Constriction-Induced Myocardial Hypertrophy: The Key Role of miR-185-5p/SREBP2-Mediated Autophagy [Letter].","authors":"Istianah Purnamasari, Yuyun Sri Wahyuni, Hernawati Basir","doi":"10.2147/DDDT.S498092","DOIUrl":"10.2147/DDDT.S498092","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4705-4706"},"PeriodicalIF":4.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Trends in Oliceridine (TRV130) Research from 2013 to 2024: A Bibliometrics and Knowledge Graph Analysis.","authors":"Cong Wang, Lidan Liu, Xue Bai","doi":"10.2147/DDDT.S475205","DOIUrl":"10.2147/DDDT.S475205","url":null,"abstract":"<p><strong>Purpose: </strong>The adverse effects and drug abuse issues associated with opioid drugs have made finding a safe and effective alternative a focus of research. Oliceridine has attracted attention for its lower adverse reactions, such as respiratory depression and gastrointestinal issues, compared to traditional opioids, and is considered a promising candidate for addressing the current limitations in opioid therapy. This article explored the knowledge structure of oliceridine through bibliometric analysis, highlighting its clinical applications in managing acute pain and its mechanisms that may reduce addiction risk. Our bibliometric analysis highlighted hotspots and trends in oliceridine research, guiding future studies on its safety and efficacy in pain management.</p><p><strong>Methods: </strong>This study utilized the Web of Science Core Collection database to search for articles related to oliceridine from 2013 to 2024. Systematic analysis was conducted on publication, country, institution, author, journal, references, and keywords. The software Citespace, Vosviewer, and Bibliometrix were employed to visualize bibliometric analysis.</p><p><strong>Results: </strong>From 2013 to 2024, 159 articles on oliceridine were published in 98 journals by 158 institutions from 28 countries. The United States has rapidly developed in this field, providing significant momentum. Keyword clustering analysis revealed that research on oliceridine primarily focused on exploring its molecular and pharmacological mechanisms and conducting clinical studies to evaluate its efficacy and safety in pain management. Analyses of the strongest citation bursts with references and keywords indicated that protein-biased ligands and oliceridine were hotspots. The emergence of divergent views regarding oliceridine's biased agonism will lead to future hotspots focusing on the underlying mechanisms of biased signaling by G protein-coupled receptors and drug design.</p><p><strong>Conclusion: </strong>Bibliometric analysis provides insights into the current hotspots and emerging areas of oliceridine, which can guide future research. The widespread attention and clinical application of oliceridine lay a solid foundation for further drug development and clinical trials.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4681-4692"},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Strategies Enhancing Bioavailability and Therapeutical Potential of Silibinin for Treatment of Liver Disorders.","authors":"Michal Selc, Radka Macova, Andrea Babelova","doi":"10.2147/DDDT.S483140","DOIUrl":"https://doi.org/10.2147/DDDT.S483140","url":null,"abstract":"<p><p>Silibinin, a bioactive component found in milk thistle extract (<i>Silybum marianum</i>), is known to have significant therapeutic potential in the treatment of various liver diseases. It is considered a key element of silymarin, which is traditionally used to support liver function. The main mechanisms of action of silibinin are attributed to its antioxidant properties protecting liver cells from damage caused by free radicals. Experimental studies conducted in vitro and in vivo have confirmed its ability to inhibit inflammatory and fibrotic processes, as well as promote the regeneration of damaged liver tissue. Therefore, silibinin represents a promising tool for the treatment of liver diseases. Since the silibinin molecule is insoluble in water and has poor bioavailability in vivo, new perspectives on solving this problem are being sought. The two most promising approaches are the water-soluble derivative silibinin-C-2',3-dihydrogen succinate, disodium salt, and the silibinin-phosphatidylcholine complex. Both drugs are currently under evaluation in liver disease clinical trials. Nevertheless, the mechanism underlying silibinin biological activity is still elusive and its more detailed understanding would undoubtedly increase its potential in the development of effective therapeutic strategies against liver diseases. This review is focused on the therapeutic potential of silibinin and its derivates, approaches to increase the bioavailability and the benefits in the treatment of liver diseases that have been achieved so far. The review discusses the relevant in vitro and in vivo studies that investigated the protective effects of silibinin in various forms of liver damage.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4629-4659"},"PeriodicalIF":4.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Dichloroacetophenone-Based PDHK1 Inhibitors as Potent Anticancer Agents.","authors":"Puhua Wu, Zhicheng Zhang, Yan Zhou, Quan Liu, Kin-Yip Tam, Zhenhong Su","doi":"10.2147/DDDT.S473437","DOIUrl":"https://doi.org/10.2147/DDDT.S473437","url":null,"abstract":"<p><strong>Background: </strong>Pyruvate dehydrogenase kinases (PDHKs), important metabolic and abnormally expressed enzymes in cancer cells, are promising targets for cancer therapy, especially for non-small-cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>In this study, a new hit, dichloroacetophenone (DAP) analog <b>9</b>, was postulated to bind to the PDHK1 allosteric pocket, guided by molecular modeling and kinase biochemical experiments. Based on this binding mode, novel DAP analogs were designed and synthesized to confirm the importance of Phe180, Tyr411, and the hydrophobic core at the bottom of the pocket.</p><p><strong>Results: </strong>This structure-activity relationship (SAR) study led to the discovery of a novel potent hybrid scaffold, dichloroacetophenone biphenylsulfone ether. Dichloroacetophenone biphenylsulfone ether <b>31</b> and <b>32</b> inhibited PDHK1 with IC₅₀ values of 86 and 140 nM, respectively.</p><p><strong>Conclusion: </strong>Compound <b>32</b> with acceptable <i>in</i> <i>vitro</i> metabolic stability, predicted drug-likeness properties and ADME/T profiles, showed promising therapeutic efficacy in a lung cancer xenograft mouse model.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4661-4679"},"PeriodicalIF":4.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Remimazolam and Propofol for Postoperative Anesthesia Satisfaction in Outpatient Gynecological Surgery: A Randomized Clinical Trial.","authors":"Xu-Lin Wang, Ling-Ling Dai, Yan-Na Li, Jian-Wen Zhang, Ming-Cui Qu, Yao-Yao Zhou, Na Xing","doi":"10.2147/DDDT.S483029","DOIUrl":"10.2147/DDDT.S483029","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare the efficacy of remimazolam and propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery.</p><p><strong>Patients and methods: </strong>This was a single-center, open-label, non-inferiority, randomized clinical trial. Patients aged ≥ 18 years who underwent outpatient gynecological surgery with sedation were enrolled. Participants were randomly assigned to be sedated with remimazolam or propofol. The primary endpoint was the immediate postoperative anesthesia satisfaction score, evaluated through the Iowa Satisfaction with Anesthesia Scale (ISAS).</p><p><strong>Results: </strong>168 patients were randomly allocated to either the remimazolam group (n = 84) or the propofol group (n = 84). The mean (standard deviation) ISAS scores immediately after surgery were 1.7 (0.6) for the remimazolam group and 2.0 (0.7) for the propofol group (difference, -0.2; 97.5% confidence interval [CI]: -0.5 to -0.0; <i>p</i> = 0.02), indicating non-inferiority. The length of post-anesthesia care unit (PACU) stay was longer in the remimazolam group than in the propofol group (27.6 [9.1] min vs 22.4 [7.0] min; difference, 5.2 [95% CI: 2.7 to 7.6] min; <i>p</i> < 0.001). High-intensity injection pain was less frequently observed in the remimazolam group than in the propofol group (3.6% vs 45.2%; difference, -41.7% [95% CI: -54.2% to -29.1%]; <i>p</i> < 0.001). The nausea score was higher in the remimazolam group immediately after surgery than in the propofol group. Pain, nausea, sleep quality, anxiety, and depression scores were higher in the remimazolam group than in the propofol group on postoperative day 1. The incidence of adverse events and other secondary endpoints was comparable between the two groups.</p><p><strong>Conclusion: </strong>Remimazolam was non-inferior to propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery. Therefore, it should be considered as a new sedation alternative in such procedures.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4615-4627"},"PeriodicalIF":4.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Pharmacokinetic Drug-Drug Interactions Involving Anlotinib as a Victim by Using Physiologically Based Pharmacokinetic Modeling.","authors":"Fengjiao Bu, Yong-Soon Cho, Qingfeng He, Xiaowen Wang, Saurav Howlader, Dong-Hyun Kim, Mingshe Zhu, Jae Gook Shin, Xiaoqiang Xiang","doi":"10.2147/DDDT.S480402","DOIUrl":"10.2147/DDDT.S480402","url":null,"abstract":"<p><strong>Background: </strong>Anlotinib was approved as a third line therapy for advanced non-small cell lung cancer in China. However, the impact of concurrent administration of various clinical drugs on the drug-drug interaction (DDI) potential of anlotinib remains undetermined. As such, this study aims to evaluate the DDI of anlotinib as a victim by establishing a physiologically based pharmacokinetic (PBPK) model.</p><p><strong>Methods: </strong>The PBPK model of anlotinib as a victim drug was constructed and validated in the Simcyp^® incorporating parameters derived from in vitro studies, pre-clinical investigations, and clinical research encompassing patients with cancer. Subsequently, plasma exposure of anlotinib in cancer patients was predicted for single- and multi-dose co-administration with typical perpetrators mentioned in Food and Drug Administration (FDA) industrial guidance.</p><p><strong>Results: </strong>Based on predictions, the CYP3A potent inhibitor ketoconazole demonstrated the most significant DDI with anlotinib, regardless of whether anlotinib is administered as a single dose or multiple doses. Ketoconazole increased the area under the concentration-time curve (AUC) and maximum concentration (C_max) of single-dose anlotinib to 1.41-fold and 1.08-fold, respectively. In contrast, rifampicin, a potent inducer of CYP3A enzymes, exhibited a relatively higher level of DDI, with AUC_R and C_maxR values of 0.44 and 0.79, respectively.</p><p><strong>Conclusion: </strong>Based on the PBPK modeling, there is a low risk of DDI between anlotinib and potent CYP3A/1A2 inhibitors, but caution and enhanced monitoring for adverse reactions are advised. To mitigate the risk of anti-tumor treatment failure, it is recommended to avoid concurrent use of strong CYP3A inducers. In conclusion, our study enhances understanding of anlotinib's interaction with medications, aiding scientists, prescribers, and drug labels in gauging the expected impact of CYP3A/1A2 modulators on anlotinib's pharmacokinetics.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4585-4600"},"PeriodicalIF":4.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical Characterization and Synergistic Antibacterial Effects of <i>Colebrookea Oppositifolia</i> Essential Oil as Adjuvants to Modern Antibiotics in Combating Drug Resistance.","authors":"Zifang Shang, Vipasha Sharma, Tarun Kumar, Kamal Dev, Sandip Patil","doi":"10.2147/DDDT.S489517","DOIUrl":"10.2147/DDDT.S489517","url":null,"abstract":"<p><strong>Background: </strong>The global threat of multi-drug-resistant bacteria has severely limited the options available for effective antibiotics. This study focuses on the antimicrobial activity and phytochemical characterization of <i>C. oppositifolia</i> extracts, aiming to identify novel plant-based therapeutic agents.</p><p><strong>Methods: </strong><i>C. oppositifolia</i> specimens-leaves and inflorescence. Specimens were cleaned, sterilized, dried, and ground into a fine powder. Extracts were obtained using methanol and petroleum ether via a Soxhlet apparatus, followed by fractionation with chloroform, n-butanol, and ethyl acetate. Volatile oil was extracted through hydro distillation using a Clevenger apparatus. Phytochemical analysis was conducted to identify bioactive compounds. Biophysical techniques, including UV-visible spectrophotometry, TLC, HPLC, GC-MS, FTIR, and NMR, were employed for characterization. Antimicrobial activity was tested against <i>S. aureus</i> ATCC25922 and <i>E. coli</i> ATCC25922 using agar well and disc diffusion methods, and synergistic effects were assessed with erythromycin and amoxicillin.</p><p><strong>Results: </strong>Methanol extract exhibited bacteriostatic activity with inhibition zones of 13.0 ± 0.2 mm for both <i>S. aureus</i> and <i>E. coli</i>. Petroleum ether, chloroform, n-butanol, and ethyl acetate fractions showed varying inhibition zones. Erythromycin demonstrated bactericidal activity, which was enhanced synergistically when combined with methanol extract and volatile oil, increasing inhibition zones against <i>S. aureus</i>. Phytochemical analysis identified phenols, flavonoids, tannins, coumarins, alkaloids, terpenoids, saponins, and glycosides. FTIR analysis revealed functional groups such as amines, aldehydes, nitriles, alkenes, and sulfones. GC-MS identified 24 compounds, with α-pinene, caryophyllene, and carene as major components. NMR spectra indicated no complex formation between oils and antibiotics, suggesting the compounds act as synergists.</p><p><strong>Conclusion: </strong>The <i>C. oppositifolia</i> extracts possess significant antimicrobial activity and synergistic potential, particularly against <i>S. aureus</i>. The presence of various bioactive compounds suggests a promising role in developing new plant-based therapeutics.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4601-4614"},"PeriodicalIF":4.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}