Pharmaceuticals (Basel, Switzerland)最新文献

{"title":"Lurasidone versus Quetiapine for Cognitive Impairments in Young Patients with Bipolar Depression: A Randomized, Controlled Study.","authors":"Xiangyuan Diao,&nbsp;Dan Luo,&nbsp;Dandan Wang,&nbsp;Jianbo Lai,&nbsp;Qunxiao Li,&nbsp;Peifen Zhang,&nbsp;Huimin Huang,&nbsp;Lingling Wu,&nbsp;Shaojia Lu,&nbsp;Shaohua Hu","doi":"10.3390/ph15111403","DOIUrl":"https://doi.org/10.3390/ph15111403","url":null,"abstract":"<p><p>The clinical efficacy of lurasidone and quetiapine, two commonly prescribed atypical antipsychotics for bipolar depression, has been inadequately studied in young patients. In this randomized and controlled study, we aimed to compare the effects of these two drugs on cognitive function, emotional status, and metabolic profiles in children and adolescents with bipolar depression. We recruited young participants (aged 10-17 years old) with a <i>DSM-5</i> diagnosis of bipolar disorder during a depressive episode, who were then randomly assigned to two groups and treated with flexible doses of lurasidone (60 to 120 mg/day) or quetiapine (300 to 600 mg/day) for consecutive 8 weeks, respectively. All the participants were clinically evaluated on cognitive function using the THINC-it instrument at baseline and week 8, and emotional status was assessed at baseline and the end of week 2, 4, and 8. Additionally, the changes in weight and serum metabolic profiles (triglyceride, cholesterol, and fasting blood glucose) during the trial were also analyzed. In results, a total of 71 patients were randomly assigned to the lurasidone group (<i>n</i> = 35) or the quetiapine group (<i>n</i> = 36), of which 31 patients completed the whole treatment course. After an 8-week follow-up, participants in the lurasidone group showed better performance in the Symbol Check Reaction and Accuracy Tests, when compared to those in the quetiapine group. No inter-group difference was observed in the depression scores, response rate, or remission rate throughout the trial. In addition, there was no significant difference in serum metabolic profiles between the lurasidone group and the quetiapine group, including triglyceride level, cholesterol level, and fasting blood glucose level. However, the quetiapine group presented a more apparent change in body weight than the lurasidone group. In conclusion, the present study provided preliminary evidence that quetiapine and lurasidone had an equivalent anti-depressive effect, and lurasidone appeared to be superior to quetiapine in improving the cognitive function of young patients with bipolar depression.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40483289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into HPLC-MS/MS Analysis, Antioxidant and Cytotoxic Activity of <i>Astragalus fruticosus</i> against Different Types of Cancer Cell Lines.","authors":"Mohamed Fayez Dekinash,&nbsp;Tarek M Okda,&nbsp;Ehab Kotb Elmahallawy,&nbsp;Fathy Kandil El-Fiky,&nbsp;Gamal Abd El Hay Omran,&nbsp;Emil Svajdlenka,&nbsp;Naief Dahran,&nbsp;Manal F El-Khadragy,&nbsp;Wafa A Al-Megrin,&nbsp;El Moataz Bellah Ali El Naggar","doi":"10.3390/ph15111406","DOIUrl":"https://doi.org/10.3390/ph15111406","url":null,"abstract":"<p><p>Plants from the genus <i>Astragalus</i> are gaining attention for their pharmacological importance. However, the information available regarding the HPLC-MS/MS chemical profile of <i>A. fruticosus</i> is inadequate. In this study, we performed HPLC-MS/MS analysis using electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). We tentatively identified 11 compounds in the <i>A. fruticosus</i> methanolic extract, including five flavonoidal and six saponin glycosides. The extract showed moderate antioxidant activity with 21.05% reduction in DPPH UV absorption. The preliminary cytotoxic screening against seven human cancer cell lines using 100 μg/mL extract showed prominent cytotoxic potential against colorectal cancer HCT-116 with 3.368% cell viability. It also showed moderate cytotoxic potential against prostate (DU-145), ovarian (SKOV-3) and lung (A-549) cancer cell lines with cell viability of 14.25%, 16.02% and 27.24%, respectively. The IC₅₀ of the total extract against HCT-116 and DU-145 cell lines were 7.81 μg/mL and 40.79 μg/mL, respectively. The observed cytotoxicity of the total methanolic extract from the leaves against colorectal cancer might facilitate future investigations on cytotoxic agent(s) for disease management.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40483292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topiramate Reprofiling for the Attenuation of Cadmium-Induced Testicular Impairment in Rats: Role of NLRP3 Inflammasome and AMPK/mTOR-Linked Autophagy.","authors":"Hany H Arab,&nbsp;Hayat A Abd El Aal,&nbsp;Shuruq E Alsufyani,&nbsp;Azza A K El-Sheikh,&nbsp;El-Shaimaa A Arafa,&nbsp;Ahmed M Ashour,&nbsp;Ahmed M Kabel,&nbsp;Ahmed H Eid","doi":"10.3390/ph15111402","DOIUrl":"https://doi.org/10.3390/ph15111402","url":null,"abstract":"<p><p>Topiramate, a promising drug classically used for the management of neurological disorders including epilepsy and migraine, has demonstrated marked anti-inflammatory and anti-apoptotic actions in murine models of cardiac post-infarction inflammation, wound healing, and gastric/intestinal injury. However, its potential impact on cadmium-induced testicular injury remains to be elucidated. Herein, the present study aimed to explore the effect of topiramate against cadmium-invoked testicular impairment with emphasis on the molecular mechanisms linked to inflammation, apoptosis, and autophagy. Herein, administration of topiramate (50 mg/kg/day, by gavage) continued for 60 days and the testes were examined by histology, immunohistochemistry, and biochemical assays. The present data demonstrated that serum testosterone, sperm count/abnormalities, relative testicular weight, and histopathological aberrations were improved by topiramate administration to cadmium-intoxicated rats. The rescue of testicular dysfunction was driven by multi-pronged mechanisms including suppression of NLRP3/caspase-1/IL-1β cascade, which was evidenced by dampened caspase-1 activity, lowered IL-1β/IL-18 production, and decreased nuclear levels of activated NF-κBp65. Moreover, curbing testicular apoptosis was seen by lowered Bax expression, decreased caspase-3 activity, and upregulation of Bcl-2. In tandem, testicular autophagy was activated as seen by diminished p62 SQSTM1 accumulation alongside Beclin-1 upregulation. Autophagy activation was associated with AMPK/mTOR pathway stimulation demonstrated by decreased mTOR (Ser2448) phosphorylation and increased AMPK (Ser487) phosphorylation. In conclusion, combating inflammation/apoptosis and enhancing autophagic events by topiramate were engaged in ameliorating cadmium-induced testicular impairment.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asian Pigeonwing Plants (<i>Clitoria ternatea</i>) Synergized Mesenchymal Stem Cells by Modulating the Inflammatory Response in Rats with Cisplatin-Induced Acute Kidney Injury.","authors":"Fatmah A Safhi,&nbsp;Salha M ALshamrani,&nbsp;Areej S Jalal,&nbsp;Nabil S Awad,&nbsp;Hussein Sabit,&nbsp;Fathy Elsayed Abdelgawad,&nbsp;Sama S Khalil,&nbsp;Dina M Khodeer,&nbsp;Maysa A Mobasher","doi":"10.3390/ph15111396","DOIUrl":"https://doi.org/10.3390/ph15111396","url":null,"abstract":"<p><p>Acute kidney injury is a heterogeneous set of disorders distinguished by a sudden decrease in the glomerular filtration rate, which is evidenced by an increase in the serum creatinine concentration or oliguria and categorized by stage and cause. It is an ever-growing health problem worldwide, with no reliable treatment. In the present study, we evaluated the role of <i>Clitoria ternatea</i> combined with mesenchymal stem cells in treating cisplatin-induced acute kidney injury in rats. Animals were challenged with cisplatin, followed by 400 mg/kg of Asian pigeonwing extract and/or mesenchymal stem cells (106 cells/150 g body weight). Kidney functions and enzymes were recorded, and histopathological sectioning was also performed. The expression profile of IL-1β, IL-6, and caspase-3 was assessed using the quantitative polymerase chain reaction. The obtained data indicated that mesenchymal stem cells combined with the botanical extract modulated the creatinine uric acid and urea levels. Cisplatin increased the level of malondialdehyde and decreased the levels of both superoxide dismutase and glutathione; however, the dual treatment was capable of restoring the normal levels. Furthermore, all treatments modulated the IL-6, IL-1β, and caspase-3 gene expression profiles. The obtained data shed some light on adjuvant therapy using <i>C. ternatea</i> and mesenchymal stem cells in treating acute kidney injury; however, further investigations are required to understand these agents' synergistic mechanisms fully. The total RNA was extracted from the control, the positive control, and all of the therapeutically treated animals. The expression profiles of the IL-6, IL-1β, and caspase-3 genes were evaluated using the real-time polymerase chain reaction. Cisplatin treatment caused a significant upregulation in IL-6. All treatments could mitigate the IL-6-upregulating effect of cisplatin, with the mesenchymal stem cell treatment being the most effective. The same profile was observed in the IL-1β and caspase-3 genes, except that the dual treatment (mesenchymal stem cells and the botanical extract) was the most effective in ameliorating the adverse effect of cisplatin; it downregulated caspase-3 expression better than the positive control.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commercially Available Enteric Empty Hard Capsules, Production Technology and Application.","authors":"Aleš Franc,&nbsp;David Vetchý,&nbsp;Nicole Fülöpová","doi":"10.3390/ph15111398","DOIUrl":"https://doi.org/10.3390/ph15111398","url":null,"abstract":"<p><p>Currently, there is a growing need to prepare small batches of enteric capsules for individual therapy or clinical evaluation since many acidic-sensitive substances should be protected from the stomach's acidic environment, including probiotics or fecal material, in the fecal microbiota transplantation (FMT) process. A suitable method seems to be the encapsulation of drugs or lyophilized alternatively frozen biological suspensions in commercial hard enteric capsules prepared by so-called Enteric Capsule Drug Delivery Technology (ECDDT). Manufacturers supply these types of capsules, made from pH-soluble polymers, in products such as AR Caps^®, EnTRinsic^TM, and Vcaps^® Enteric, or capsules made of gelling polymers that release their content as the gel erodes over time when passing through the digestive tract. These include DRcaps^®, EMBO CAPS^® AP, BioVXR^®, or ACGcaps™ HD. Although not all capsules in all formulations meet pharmaceutical requirements for delayed-release dosage forms in disintegration and dissolution tests, they usually find practical application. This literature review presents their composition and properties. Since ECDDT is a new technology, this article is based on a limited number of references.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical Composition of <i>Impatiens textori</i> Miq. Flower Absolute and Its Potential Wound Repair and Anti-Melanogenesis-Promoting Activities in Skin Cells.","authors":"Yu Rim Won,&nbsp;Kyung Jong Won,&nbsp;Do Yoon Kim,&nbsp;Mi Jung Kim,&nbsp;Bok Sil Hong,&nbsp;Hwan Myung Lee","doi":"10.3390/ph15111397","DOIUrl":"https://doi.org/10.3390/ph15111397","url":null,"abstract":"<p><p><i>Impatiens textori</i> Miq. (ITM; family Balsaminaceae) is a traditional medicinal plant with many biological activities, which include anti-allergic, anti-inflammatory, and anti-pruritic properties. However, it remains to be determined whether ITM affects biological activities in the skin. Thus, we investigated the effects of ITM flower absolute (ITMFAb) extract on the biological activities of skin, especially those related to skin wound repair and whitening. ITMFAb was extracted with hexane, and its composition was determined through GC/MS. The biological activities of ITMFAb on HaCaT keratinocytes and B16BL6 melanoma cells were analyzed using a water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, a Boyden chamber, an ELISA, a sprouting assay, and by immunoblotting. These analyses were performed in a range of ITMFAb concentrations that did not inhibit the viability of the cells (HaCaT, ≤400 µg/mL; B16BL6, ≤200 µg/m). Forty components were identified in ITMFAb. ITMFAb stimulated proliferation, migration, sprout outgrowth, and type I and IV collagen synthesis and upregulated the activations of ERK1/2, JNK, p38 MAPK, and AKT in HaCaT cells. In addition, ITMFAb attenuated the serum-induced proliferation of B16BL6 cells. ITMFAb inhibited melanin synthesis, tyrosinase activity, and expressions of MITF and tyrosinase in α-MSH-exposed B16BL6 cells. These findings indicate that ITMFAb has beneficial effects on wound repairing and whitening-linked responses in the skin and suggest the potential use of ITMFAb as a natural material for the development of skin wound repair and whitening agents.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxysafflor Yellow A Phytosomes Administered via Intervaginal Space Injection Ameliorate Pulmonary Fibrosis in Mice.","authors":"Tingting Li,&nbsp;Dong Han,&nbsp;Zhongxian Li,&nbsp;Mengqi Qiu,&nbsp;Yuting Zhu,&nbsp;Kai Li,&nbsp;Jiawei Xiang,&nbsp;Huizhen Sun,&nbsp;Yahong Shi,&nbsp;Tun Yan,&nbsp;Xiaoli Shi,&nbsp;Qiang Zhang","doi":"10.3390/ph15111394","DOIUrl":"https://doi.org/10.3390/ph15111394","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis is a fatal interstitial disease characterized by fibroblast proliferation and differentiation and abnormal accumulation of extracellular matrix, with high mortality and an increasing annual incidence. Since few drugs are available for the treatment of pulmonary fibrosis, there is an urgent need for high-efficiency therapeutic drugs and treatment methods to reduce the mortality associated with pulmonary fibrosis. The interstitium, a highly efficient transportation system that pervades the body, plays an important role in the occurrence and development of disease, and can be used as a new route for disease diagnosis and treatment. In this study, we evaluated the administration of hydroxysafflor yellow A phytosomes via intervaginal space injection (ISI) as an anti-pulmonary fibrosis treatment. Our results show that this therapeutic strategy blocked the activation of p38 protein in the MAPK-p38 signaling pathway and inhibited the expression of Smad3 protein in the TGF-β/Smad signaling pathway, thereby reducing secretion of related inflammatory factors, deposition of collagen in the lungs of mice, and destruction of the alveolar structure. Use of ISI in the treatment of pulmonary fibrosis provides a potential novel therapeutic modality for the disease.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Biological Evaluation of a Fused Structure of Indolizine and Pyrrolo[1,2-<i>c</i>]pyrimidine: Identification of Its Potent Anticancer Activity against Liver Cancer Cells.","authors":"Seonghyeon Nam,&nbsp;Yechan Lee,&nbsp;So-Hyeon Park,&nbsp;Wan Namkung,&nbsp;Ikyon Kim","doi":"10.3390/ph15111395","DOIUrl":"https://doi.org/10.3390/ph15111395","url":null,"abstract":"<p><p>A highly efficient approach to a new indolizine scaffold fused with pyrrolo[1,2-<i>c</i>]pyrimidine was achieved via one-pot three-component coupling followed by an oxidative cyclization reaction. The simple two-step sequence allowed rapid access to various tetracyclic compounds from commercially available starting materials with the formation of five new bonds. Here, we observed the effects of these compounds on cell viability in HepG2, H1299, HT29, AGS, and A549 cancer cell lines. Interestingly, this fused scaffold had more potent anticancer activity in hepatocellular carcinoma HepG2 and Huh7 cells than other cancer cells. In particular, <b>5r</b> strongly decreased cell viability in HepG2 and Huh7 cells with an IC₅₀ value of 0.22 ± 0.08 and 0.10 ± 0.11 µM, respectively, but had a very weak inhibitory effect on the cell viability of other cancer cell lines. In addition, <b>5r</b> significantly inhibited cell migration and induced apoptosis in HepG2 and Huh7 cells via the activation of caspase-3 and cleavage of PARP in a dose-dependent manner. Notably, the co-treatment of <b>5r</b> with gemcitabine resulted in the significant additional inhibition of cell viability in HepG2 and Huh7 cells. Our results suggest that <b>5r</b> could be used to develop new chemotype anticancer agents against liver cancers.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40722159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Microtumor Formation of Infantile Hemangioma-Derived Endothelial Cells for Mechanistic Exploration and Drug Screening.","authors":"Yanan Li,&nbsp;Xinglong Zhu,&nbsp;Meng Kong,&nbsp;Siyuan Chen,&nbsp;Ji Bao,&nbsp;Yi Ji","doi":"10.3390/ph15111393","DOIUrl":"https://doi.org/10.3390/ph15111393","url":null,"abstract":"<p><p>Infantile hemangioma (IH) is the most prevalent type of vascular tumor in infants. The pathophysiology of IH is unknown. The tissue structure and physiology of two-dimensional cell cultures differ greatly from those in vivo, and spontaneous regression often occurs during tumor formation in nude mice and has severely limited research into the pathogenesis and development of IH. By decellularizing porcine aorta, we attempted to obtain vascular-specific extracellular matrix as the bioink for fabricating micropattern arrays of varying diameters via microcontact printing. We then constructed IH-derived CD31+ hemangioma endothelial cell three-dimensional microtumor models. The vascular-specific and decellularized extracellular matrix was suitable for the growth of infantile hemangioma-derived endothelial cells. The KEGG signaling pathway analysis revealed enrichment primarily in stem cell pluripotency, RAS, and PI3KAkt compared to the two-dimensional cell model according to RNA sequencing. Propranolol, the first-line medication for IH, was also used to test the model's applicability. We also found that metformin had some impact on the condition. The three-dimensional microtumor models of CD31+ hemangioma endothelial cells were more robust and efficient experimental models for IH mechanistic exploration and drug screening.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40722158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of N-Containing (-)-Borneol Esters as Respiratory Syncytial Virus Fusion Inhibitors.","authors":"Anastasiya S Sokolova,&nbsp;Olga I Yarovaya,&nbsp;Lana V Kuzminykh,&nbsp;Anna A Shtro,&nbsp;Artem M Klabukov,&nbsp;Anastasia V Galochkina,&nbsp;Yulia V Nikolaeva,&nbsp;Galina D Petukhova,&nbsp;Sophia S Borisevich,&nbsp;Edward M Khamitov,&nbsp;Nariman F Salakhutdinov","doi":"10.3390/ph15111390","DOIUrl":"https://doi.org/10.3390/ph15111390","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) causes acute respiratory infections, thus, posing a serious threat to the health of infants, children, and elderly people. In this study, we have discovered a series of potent RSV entry inhibitors with the (-)-borneol scaffold. The active compounds <b>3b</b>, <b>5a</b>, <b>5c</b>, <b>7b</b>, <b>9c</b>, <b>10b</b>, <b>10c</b>, and <b>14b</b> were found to exhibit activity against RSV A strain A2 in HEp-2 cells. The most active substances, <b>3b</b> (IC₅₀ = 8.9 μM, SI = 111) and <b>5a</b> (IC₅₀ = 5.0 μM, SI = 83), displayed more potency than the known antiviral agent Ribavirin (IC₅₀ = 80.0 μM, SI = 50). Time-of-addition assay and temperature shift studies demonstrated that compounds <b>3b</b>, <b>5a</b>, and <b>6b</b> inhibited RSV entry, probably by interacting with the viral F protein that mediated membrane fusion, while they neither bound to G protein nor inhibited RSV attachment to the target cells. Appling procedures of molecular modeling and molecular dynamics, the binding mode of compounds <b>3b</b> and <b>5a</b> was proposed. Taken together, the results of this study suggest (-)-borneol esters to be promising lead compounds for developing new anti-RSV agents.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40722156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}