Florfenicol (FFC) is an important and widely used veterinary drug, and its structure has been characterized by nuclear magnetic resonance (NMR) spectroscopy. The study aimed to investigate the influences of solvent type, solvent concentration, and temperature on the chemical shifts of the 1H NMR of FFC. The results showed that different types of solvents significantly affected the chemical shifts, especially the chemical shifts of 2-H, 3-H, 5-H, and the active protons. When DMSO-d 6 is used as the solvent, there is no significant difference in the chemical shifts of FFC with a concentration ranging from 20 to 250 mmol/L; however, as the temperature increases, the chemical shifts of the active protons move to a higher field. Besides, the NMR spectroscopic data and structural analysis of FFC were refined by 1H, 13C, distortionless enhancement by polarization transfer-135 (DEPT-135), 1H–1H correlation spectroscopy (1H–1H COSY), phase-sensitive gradient heteronuclear singular quantum correlation (gHSQC), and heteronuclear multiple bond correlation (gHMBC) NMR spectroscopy using DMSO-d 6 as a solvent. The study will help with qualitative and quantitative analysis of FFC in the future.
{"title":"Solvents Influence 1 H NMR Chemical Shifts and Complete 1 H and 13 C NMR Spectral Assignments for Florfenicol","authors":"Wan-Ting Ai, Wei-Ke Su, Feng Su","doi":"10.1055/s-0043-1777285","DOIUrl":"https://doi.org/10.1055/s-0043-1777285","url":null,"abstract":"Florfenicol (FFC) is an important and widely used veterinary drug, and its structure has been characterized by nuclear magnetic resonance (NMR) spectroscopy. The study aimed to investigate the influences of solvent type, solvent concentration, and temperature on the chemical shifts of the 1H NMR of FFC. The results showed that different types of solvents significantly affected the chemical shifts, especially the chemical shifts of 2-H, 3-H, 5-H, and the active protons. When DMSO-d 6 is used as the solvent, there is no significant difference in the chemical shifts of FFC with a concentration ranging from 20 to 250 mmol/L; however, as the temperature increases, the chemical shifts of the active protons move to a higher field. Besides, the NMR spectroscopic data and structural analysis of FFC were refined by 1H, 13C, distortionless enhancement by polarization transfer-135 (DEPT-135), 1H–1H correlation spectroscopy (1H–1H COSY), phase-sensitive gradient heteronuclear singular quantum correlation (gHSQC), and heteronuclear multiple bond correlation (gHMBC) NMR spectroscopy using DMSO-d 6 as a solvent. The study will help with qualitative and quantitative analysis of FFC in the future.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"2 1","pages":"e288 - e296"},"PeriodicalIF":0.0,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139367843","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}
Wei Zhang, Hong Liu, Wei-Liang Zhuang, Yuan Li, Li-ping Xie, You-Jia Hu
Abstract Triple-negative breast cancer (TNBC), which accounts for 15 to 20% of incidents of breast cancer, is the only breast cancer subtype that lacks targeted treatments. It was reported in the literature that LIV1 was highly expressed in TNBC and other solid tumors. This makes LIV1 a potential target for the treatment of TNBC. This study aimed to develop an anti-LIV1 antibody for the treatment of TNBC. In this study, a novel anti-LIV1 antibody Ab1120 was developed and conjugated with monomethyl auristatin E (MMAE) to obtain the antibody–drug conjugate, Ab1120-vcMMAE. The Cell Counting Kit-8 method was used to assess the killing effect of the antibody–drug conjugate on cell lines MDA-MB−231 (high LIV1 expression of breast cancer cell line), MDA-MB-468 (low LIV1 expression of breast cell line), and 293C18 (LIV1-negative human embryonic kidney cell). The antitumor effect of Ab1120-vcMMAE on an MDA-MB-231 xenograft model was determined by evaluating the tumor volume and body weight after its treatment. In vitro analysis showed that Ab1120-vcMMAE is a potent inhibitor against the proliferation of a LIV1 overexpression cell line. The in vivo results demonstrated its antitumor activity in the cell-derived xenograft breast tumor mouse model. The results of this study suggest that Ab1120-vcMMAE may be used as a new therapeutic drug for patients with LIV1 high-expression breast cancer.
三阴性乳腺癌(TNBC)占乳腺癌发病率的15% ~ 20%，是目前唯一缺乏靶向治疗的乳腺癌亚型。文献报道，LIV1在TNBC等实体瘤中高表达。这使得LIV1成为治疗TNBC的潜在靶点。本研究旨在开发一种治疗TNBC的抗liv1抗体。本研究制备了一种新型抗liv1抗体Ab1120，并与单甲基auristatin E (MMAE)偶联，得到抗体-药物偶联物Ab1120- vcmmae。采用细胞计数试剂盒-8法检测抗体-药物偶联物对MDA-MB−231 (LIV1高表达的乳腺癌细胞系)、MDA-MB-468 (LIV1低表达的乳腺癌细胞系)和293C18 (LIV1阴性的人胚胎肾细胞)的杀伤效果。通过评价Ab1120-vcMMAE对MDA-MB-231异种移植瘤模型治疗后的肿瘤体积和体重，确定其抗肿瘤作用。体外分析表明，Ab1120-vcMMAE是抑制LIV1过表达细胞系增殖的有效抑制剂。体内实验结果表明其在细胞源性异种乳腺肿瘤小鼠模型中具有抗肿瘤活性。本研究结果提示，Ab1120-vcMMAE可能成为LIV1高表达乳腺癌患者的一种新的治疗药物。
{"title":"A Potential Antibody–Drug Conjugate Targeting Human LIV1 for the Treatment of Triple-Negative Breast Cancer","authors":"Wei Zhang, Hong Liu, Wei-Liang Zhuang, Yuan Li, Li-ping Xie, You-Jia Hu","doi":"10.1055/s-0043-1772703","DOIUrl":"https://doi.org/10.1055/s-0043-1772703","url":null,"abstract":"Abstract Triple-negative breast cancer (TNBC), which accounts for 15 to 20% of incidents of breast cancer, is the only breast cancer subtype that lacks targeted treatments. It was reported in the literature that LIV1 was highly expressed in TNBC and other solid tumors. This makes LIV1 a potential target for the treatment of TNBC. This study aimed to develop an anti-LIV1 antibody for the treatment of TNBC. In this study, a novel anti-LIV1 antibody Ab1120 was developed and conjugated with monomethyl auristatin E (MMAE) to obtain the antibody–drug conjugate, Ab1120-vcMMAE. The Cell Counting Kit-8 method was used to assess the killing effect of the antibody–drug conjugate on cell lines MDA-MB−231 (high LIV1 expression of breast cancer cell line), MDA-MB-468 (low LIV1 expression of breast cell line), and 293C18 (LIV1-negative human embryonic kidney cell). The antitumor effect of Ab1120-vcMMAE on an MDA-MB-231 xenograft model was determined by evaluating the tumor volume and body weight after its treatment. In vitro analysis showed that Ab1120-vcMMAE is a potent inhibitor against the proliferation of a LIV1 overexpression cell line. The in vivo results demonstrated its antitumor activity in the cell-derived xenograft breast tumor mouse model. The results of this study suggest that Ab1120-vcMMAE may be used as a new therapeutic drug for patients with LIV1 high-expression breast cancer.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"14 1","pages":"e187 - e196"},"PeriodicalIF":0.0,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89533530","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}
D. E. Uti, U. Ibiam, W. A. Omang, P. A. Udeozor, G. Umoru, S. Nwadum, Inalegwu Bawa, E. Alum, J. Mordi, E. O. Okoro, U. Obeten, Eucharia N. Onwe, S. Zakari, Ohunene Rukayat Opotu, P. M. Aja
Abstract The study aimed to investigate how the solvent extract of Buchholzia coriacea (BCE), a widely known hypolipidemic agent, could contribute to hyperlipidemia treatment and identify the potential bioactive compounds. We studied Wistar albino rats, dividing them into seven groups: the normal control, normal rats treated with 400 mg/kg.b.wt of BCE (NRG group), the hyperlipidemic control (HPC group), hyperlipidemic rats treated with atorvastatin, a standard control drug (SC group), as well as 200, 400, and 800 mg/kg.b.wt of BCE extract respectively (T1, T2, T3 groups). The potential compounds that functioned in BCE extract were analyzed by in silico binding to acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). The binding affinities and drug-like properties of the compounds were determined using virtual screening and absorption distribution metabolism excretion and toxicity prediction analysis. The gas chromatography-mass spectrometry analysis identified alkaloids, saponins, flavonoids, phenols, terpenoids, and 44 chemical compounds in the leaf extract of BCE. BCE significantly reduced the levels of triacylglycerol, total cholesterol, low-density lipoprotein, very low-density lipoprotein, atherogenic coefficient, atherogenic index, and coronary risk index, while enhancing the levels of high-density lipoprotein and cardioprotective index in comparison to the HPC group. The BCE reduced malondialdehyde quantities, which exhibit high levels in HPC. Superoxide dismutase and glutathione peroxidase activities as well as glutathione levels, which are otherwise reduced in HPC, were increased upon the BCE treatment. Among the identified BCE compounds, lupenone and 2,7-dimethylnaphthalene exhibited the highest binding affinities to ACC and FASN, suggesting that these two compounds might be the bioactive BCE components displaying hypolipidemic properties. BCE is found to be beneficial in blocking hyperlipidemia through the modulation of lipid profile, the protection of cardiovascular function, as well as the suppression of oxidative stress. BCE may be a natural source for exploring novel drugs for the treatment of dyslipidemia.
{"title":"Buchholzia coriacea Leaves Attenuated Dyslipidemia and Oxidative Stress in Hyperlipidemic Rats and Its Potential Targets In Silico","authors":"D. E. Uti, U. Ibiam, W. A. Omang, P. A. Udeozor, G. Umoru, S. Nwadum, Inalegwu Bawa, E. Alum, J. Mordi, E. O. Okoro, U. Obeten, Eucharia N. Onwe, S. Zakari, Ohunene Rukayat Opotu, P. M. Aja","doi":"10.1055/s-0043-1772607","DOIUrl":"https://doi.org/10.1055/s-0043-1772607","url":null,"abstract":"Abstract The study aimed to investigate how the solvent extract of Buchholzia coriacea (BCE), a widely known hypolipidemic agent, could contribute to hyperlipidemia treatment and identify the potential bioactive compounds. We studied Wistar albino rats, dividing them into seven groups: the normal control, normal rats treated with 400 mg/kg.b.wt of BCE (NRG group), the hyperlipidemic control (HPC group), hyperlipidemic rats treated with atorvastatin, a standard control drug (SC group), as well as 200, 400, and 800 mg/kg.b.wt of BCE extract respectively (T1, T2, T3 groups). The potential compounds that functioned in BCE extract were analyzed by in silico binding to acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). The binding affinities and drug-like properties of the compounds were determined using virtual screening and absorption distribution metabolism excretion and toxicity prediction analysis. The gas chromatography-mass spectrometry analysis identified alkaloids, saponins, flavonoids, phenols, terpenoids, and 44 chemical compounds in the leaf extract of BCE. BCE significantly reduced the levels of triacylglycerol, total cholesterol, low-density lipoprotein, very low-density lipoprotein, atherogenic coefficient, atherogenic index, and coronary risk index, while enhancing the levels of high-density lipoprotein and cardioprotective index in comparison to the HPC group. The BCE reduced malondialdehyde quantities, which exhibit high levels in HPC. Superoxide dismutase and glutathione peroxidase activities as well as glutathione levels, which are otherwise reduced in HPC, were increased upon the BCE treatment. Among the identified BCE compounds, lupenone and 2,7-dimethylnaphthalene exhibited the highest binding affinities to ACC and FASN, suggesting that these two compounds might be the bioactive BCE components displaying hypolipidemic properties. BCE is found to be beneficial in blocking hyperlipidemia through the modulation of lipid profile, the protection of cardiovascular function, as well as the suppression of oxidative stress. BCE may be a natural source for exploring novel drugs for the treatment of dyslipidemia.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"70 1","pages":"e141 - e152"},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88251581","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}
Benzofuran-6-carboxylic acid 2 and 2-(tert-butoxycarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid 21 are two key intermediates for the synthesis of lifitegrast (1). The present study aimed to obtain lifitegrast from the key intermediates of 2 and 5,7-dichloro-2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (31), which had the same core structure as 21. In this study, the synthetic routes of 2 and 31 were explored. 2 and 31 were synthesized from 4-bromo-2-hydroxybenzaldehyde (25) and 2-(2,4-dichlorophenyl)ethan-1-amine (28), with the yields of 78 and 80%, respectively. The route avoided the harsh reaction conditions of generating 2 in a previous study and could more efficiently achieve the core structure of 5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid. Besides, the hydrolysis reaction conditions of preparing lifitegrast were also optimized. In this work, lifitegrast was obtained from 2 and 31 with high purity (>99.9%) and an overall yield of 79%, which was higher than the reported yield of 66%.
{"title":"An Improved Synthetic Process of Two Key Intermediates and Their Application in the Synthesis of Lifitegrast","authors":"Gang-Long Jiang, Xin-Kun Wang, Xia Xiao, Yu Liu","doi":"10.1055/s-0043-1771035","DOIUrl":"https://doi.org/10.1055/s-0043-1771035","url":null,"abstract":"Benzofuran-6-carboxylic acid 2 and 2-(tert-butoxycarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid 21 are two key intermediates for the synthesis of lifitegrast (1). The present study aimed to obtain lifitegrast from the key intermediates of 2 and 5,7-dichloro-2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (31), which had the same core structure as 21. In this study, the synthetic routes of 2 and 31 were explored. 2 and 31 were synthesized from 4-bromo-2-hydroxybenzaldehyde (25) and 2-(2,4-dichlorophenyl)ethan-1-amine (28), with the yields of 78 and 80%, respectively. The route avoided the harsh reaction conditions of generating 2 in a previous study and could more efficiently achieve the core structure of 5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid. Besides, the hydrolysis reaction conditions of preparing lifitegrast were also optimized. In this work, lifitegrast was obtained from 2 and 31 with high purity (>99.9%) and an overall yield of 79%, which was higher than the reported yield of 66%.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"28 1","pages":"e153 - e160"},"PeriodicalIF":0.0,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84367861","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}
Fang-Fang Yu, Le-Yi Huang, Man Li, Shi-Wen Cui, Jie Yuan, Xiao-feng Li, Tong Wu
Abstract Osteoporosis (OP) is a metabolic disease characterized by bone formation and resorption disturbances. Quanduzhong Capsule (QDZC) is a common treatment for OP in China; however, the effective components and metabolites of the drug after oral administration remain largely unknown. This study aims to identify the active components, analyze the metabolite changes, and investigate the underlying mechanism against OP. In the study, ovariectomy-induced rat OP model was established, then treated with QDZC. Alendronate sodium tablets (ASTs) were used as a reference drug. The chemical constituents of QDZC were analyzed by UPLC-QTOF-MS (ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry) and network pharmacology. The metabolomics was used to analyze differences in serum metabolites of rats in different groups [Sham, Model, Model + QDZC, and Model + AST] at 4, 8, and 12 weeks. Body weight and bone mineral density (BMD) were assessed. Enzyme-linked immunosorbent assay was used to determine serum levels of Akt, p-Akt, ERK, and p-ERK. Our data suggested 86 different chemicals from QDZC, including nine core compounds. QDZC significantly regulated 25 biomarkers linked to arachidonic acid metabolism and unsaturated fatty acid biosynthesis, and promoted serum expression of Akt, p-Akt, ERK, and p-ERK. QDZC might act by activating PI3K-Akt and MAPK signaling pathways. In addition, QDZC may use arachidonic acid derivatives to inhibit osteoclast generation and bone resorption and enhance calcitriol formation to improve calcium absorption and increase bone mass.
{"title":"Evaluation of Biological Mechanisms of Quanduzhong Capsule for Treating Osteoporosis by Integrating Untargeted Metabolomics and Network Pharmacology","authors":"Fang-Fang Yu, Le-Yi Huang, Man Li, Shi-Wen Cui, Jie Yuan, Xiao-feng Li, Tong Wu","doi":"10.1055/s-0043-1771048","DOIUrl":"https://doi.org/10.1055/s-0043-1771048","url":null,"abstract":"Abstract Osteoporosis (OP) is a metabolic disease characterized by bone formation and resorption disturbances. Quanduzhong Capsule (QDZC) is a common treatment for OP in China; however, the effective components and metabolites of the drug after oral administration remain largely unknown. This study aims to identify the active components, analyze the metabolite changes, and investigate the underlying mechanism against OP. In the study, ovariectomy-induced rat OP model was established, then treated with QDZC. Alendronate sodium tablets (ASTs) were used as a reference drug. The chemical constituents of QDZC were analyzed by UPLC-QTOF-MS (ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry) and network pharmacology. The metabolomics was used to analyze differences in serum metabolites of rats in different groups [Sham, Model, Model + QDZC, and Model + AST] at 4, 8, and 12 weeks. Body weight and bone mineral density (BMD) were assessed. Enzyme-linked immunosorbent assay was used to determine serum levels of Akt, p-Akt, ERK, and p-ERK. Our data suggested 86 different chemicals from QDZC, including nine core compounds. QDZC significantly regulated 25 biomarkers linked to arachidonic acid metabolism and unsaturated fatty acid biosynthesis, and promoted serum expression of Akt, p-Akt, ERK, and p-ERK. QDZC might act by activating PI3K-Akt and MAPK signaling pathways. In addition, QDZC may use arachidonic acid derivatives to inhibit osteoclast generation and bone resorption and enhance calcitriol formation to improve calcium absorption and increase bone mass.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"27 1","pages":"e197 - e208"},"PeriodicalIF":0.0,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81221648","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}
Abstract A previously established flashing jet inhaler prototype (FJ prototype) can produce an aqueous aerosol but cannot steadily provide inhalable aerosol (2–5 μm). This study aims to optimize the atomization performance of the FJ prototype and generate inhalable aqueous aerosols. The effects of overheat degree, jetting rate, jetting volume, and liquid type on atomization performance were assessed by determining output aerosol's mass median aerodynamic diameter (MMAD) and aerodynamic particle size distribution. Drug distribution of active ingredients in different liquid types was also measured. A Pari nebulizer was used as a reference device. Our data suggested that MMAD is negatively correlated with the overheat degree and jetting rate, but has no significant relationship with the jetting volume. The effect of jetting rate is weaker than that of the overheat degree. When normal saline was used as the atomization liquid, output aerosol's MMAD at the FJ prototype and Pari nebulizer were 1.98 ± 0.18 and 2.50 ± 0.81 μm, respectively. The addition of a surfactant significantly decreases MMAD both in solution and in suspension, but the suspended particles had no effect on the residual level and atomization performance of the FJ prototype. When ventolin was used as the atomization liquid, the MMAD of the FJ prototype and Pari nebulizer was 2.1 ± 0.2 and 1.7 ± 0.2 μm, respectively, while the fine particle dosage (FPD) in percent of the nominal dose (%ND) was 50.4 ± 3.1 and 53.1 ± 7.2%, respectively. When pulmicort respules was used as the atomization liquid, the MMAD of the FJ prototype and Pari nebulizer was 2.5 ± 0.5 and 4.6 ± 0.2 μm respectively, while the FPD (%ND) was 30.1 ± 5.6 and 58.6 ± 5.1%, respectively. The FJ prototype not only delivers inhalable aqueous aerosol but also has a potential advantage in the atomization of suspension or poorly soluble drugs.
{"title":"A Technical Feasibility of Aqueous Aerosol Generation Based on the Flashing Jet: Effects of Overheat Degree, Jetting Rate, Jetting Volume, and Liquid Type","authors":"Qiang Zheng, Li-Jia Yuan, Jian Wang","doi":"10.1055/s-0043-1772193","DOIUrl":"https://doi.org/10.1055/s-0043-1772193","url":null,"abstract":"Abstract A previously established flashing jet inhaler prototype (FJ prototype) can produce an aqueous aerosol but cannot steadily provide inhalable aerosol (2–5 μm). This study aims to optimize the atomization performance of the FJ prototype and generate inhalable aqueous aerosols. The effects of overheat degree, jetting rate, jetting volume, and liquid type on atomization performance were assessed by determining output aerosol's mass median aerodynamic diameter (MMAD) and aerodynamic particle size distribution. Drug distribution of active ingredients in different liquid types was also measured. A Pari nebulizer was used as a reference device. Our data suggested that MMAD is negatively correlated with the overheat degree and jetting rate, but has no significant relationship with the jetting volume. The effect of jetting rate is weaker than that of the overheat degree. When normal saline was used as the atomization liquid, output aerosol's MMAD at the FJ prototype and Pari nebulizer were 1.98 ± 0.18 and 2.50 ± 0.81 μm, respectively. The addition of a surfactant significantly decreases MMAD both in solution and in suspension, but the suspended particles had no effect on the residual level and atomization performance of the FJ prototype. When ventolin was used as the atomization liquid, the MMAD of the FJ prototype and Pari nebulizer was 2.1 ± 0.2 and 1.7 ± 0.2 μm, respectively, while the fine particle dosage (FPD) in percent of the nominal dose (%ND) was 50.4 ± 3.1 and 53.1 ± 7.2%, respectively. When pulmicort respules was used as the atomization liquid, the MMAD of the FJ prototype and Pari nebulizer was 2.5 ± 0.5 and 4.6 ± 0.2 μm respectively, while the FPD (%ND) was 30.1 ± 5.6 and 58.6 ± 5.1%, respectively. The FJ prototype not only delivers inhalable aqueous aerosol but also has a potential advantage in the atomization of suspension or poorly soluble drugs.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"148 1","pages":"e175 - e186"},"PeriodicalIF":0.0,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82627509","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}
The γ-ketoaldehyde functionality of levuglandins (LGs) has a great propensity for various diseases such as Alzheimer's, atherosclerosis, and renal diseases. The synthesis of LGs constitutes a challenge for synthetic organic chemists due to their complex structures and low abundance in nature which has prompted us to develop its quick synthesis. This study aimed to explore a novel route for the construction of a levuglandin skeleton. We envisaged that the photocycloaddition of an appropriate alkene with equivalent propyne would give the cyclobutene adduct. The oxidative cleavage of the photocycloadduct can lead to the formation of the keto-aldehyde functionality. In this study, the readily available isopropenyl acetate (5) and methyl oleate (6) were used as starting materials to synthesize the target compound 13. The key step involves photocycloaddition of compounds 5 and 6, a regio-controlled elimination of the hydroxy group of compound 10, forming a cyclobutene derivative, as well as an oxidative cleavage of the cyclobutene derivative gives the framework of levuglandin. The intriguing chemistry of elimination resulting in the inseparable mixture of regioisomeric cyclobutenes has also been discussed. The route was simple and economical and helped for the creation of γ-ketoaldehyde functionality which is vital for the activity of levuglandins and can be extended for the construction of prostanoid skeleton through aldol condensation of the γ-ketoaldehydes.
{"title":"A Short and Facile [2 + 2] Photocycloaddition Protocol Toward Construction of a Levuglandin Skeleton","authors":"Pradeep Deota, Deepak Singh, Gaurang J Bhatt","doi":"10.1055/s-0043-1772224","DOIUrl":"https://doi.org/10.1055/s-0043-1772224","url":null,"abstract":"The γ-ketoaldehyde functionality of levuglandins (LGs) has a great propensity for various diseases such as Alzheimer's, atherosclerosis, and renal diseases. The synthesis of LGs constitutes a challenge for synthetic organic chemists due to their complex structures and low abundance in nature which has prompted us to develop its quick synthesis. This study aimed to explore a novel route for the construction of a levuglandin skeleton. We envisaged that the photocycloaddition of an appropriate alkene with equivalent propyne would give the cyclobutene adduct. The oxidative cleavage of the photocycloadduct can lead to the formation of the keto-aldehyde functionality. In this study, the readily available isopropenyl acetate (5) and methyl oleate (6) were used as starting materials to synthesize the target compound 13. The key step involves photocycloaddition of compounds 5 and 6, a regio-controlled elimination of the hydroxy group of compound 10, forming a cyclobutene derivative, as well as an oxidative cleavage of the cyclobutene derivative gives the framework of levuglandin. The intriguing chemistry of elimination resulting in the inseparable mixture of regioisomeric cyclobutenes has also been discussed. The route was simple and economical and helped for the creation of γ-ketoaldehyde functionality which is vital for the activity of levuglandins and can be extended for the construction of prostanoid skeleton through aldol condensation of the γ-ketoaldehydes.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"40 1","pages":"e168 - e174"},"PeriodicalIF":0.0,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89246160","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}
Abstract Treatment of sickle cell disease (SCD) remains largely palliative. While it can enhance living standards, persons having SCD still suffer from extreme sickling crises, end-organ destruction, and reduced life expectancy. Increasing research has resulted in the recognition and advancement of stem cell transplantation and gene therapy as possible solutions for SCDs. However, there have been various factors that have hindered their clinical application. The more advantageous of the two, stem cell transplantation, is constrained by a small donor pool, transplant difficulties, and eligibility requirements. The current article reviewed the literature on SCDs, current treatment options, and more particularly the progress of stem cell transplants. It outlined various challenges of stem cell transplant and proposed ways to increase the donor pool using alternative strategies and modifications of regimen conditioning with minimal transplant-related toxicities and associated complications.
{"title":"The Present Condition of Sickle Cell Disease: An Overview of Stem Cell Transplantation as a Cure","authors":"Md Sadique Hussain, Varunesh Chaturvedi","doi":"10.1055/s-0043-1768918","DOIUrl":"https://doi.org/10.1055/s-0043-1768918","url":null,"abstract":"Abstract Treatment of sickle cell disease (SCD) remains largely palliative. While it can enhance living standards, persons having SCD still suffer from extreme sickling crises, end-organ destruction, and reduced life expectancy. Increasing research has resulted in the recognition and advancement of stem cell transplantation and gene therapy as possible solutions for SCDs. However, there have been various factors that have hindered their clinical application. The more advantageous of the two, stem cell transplantation, is constrained by a small donor pool, transplant difficulties, and eligibility requirements. The current article reviewed the literature on SCDs, current treatment options, and more particularly the progress of stem cell transplants. It outlined various challenges of stem cell transplant and proposed ways to increase the donor pool using alternative strategies and modifications of regimen conditioning with minimal transplant-related toxicities and associated complications.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"34 1","pages":"e57 - e63"},"PeriodicalIF":0.0,"publicationDate":"2023-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79182411","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}
Abstract Co-crystals can improve the physicochemical properties of pharmaceutical active ingredients, and thus have great potential in improving drug performance. Some studies have obtained the powder spectrum of the co-crystal of flurbiprofen (FBP) and salicylamide (2-OHBZA) but have not obtained a single-crystal structure. In this study, co-crystals of FBP-2-OHBZA with a molar ratio of 1:1 were obtained by slow evaporation using ethyl acetate and tetrahydrofuran for verification. Density functional theory was used to optimize the structure of the hydrogen bond and π−π stacking formed by the co-crystal of FBP and 2-OHBZA. The assay results of the co-crystals of FBP-2-OHBZA are in good agreement with the calculated values reported.
{"title":"Preparation and Study on the Single-Crystal Structure of Flurbiprofen–Salicylamide Co-crystal","authors":"Jia-Wei Hou, Yan-qing Gong, Gang Li, Li-Wen Ma, Hong-Juan Pan, Hanbin Shan, Jia-liang Zhong","doi":"10.1055/s-0043-1769006","DOIUrl":"https://doi.org/10.1055/s-0043-1769006","url":null,"abstract":"Abstract Co-crystals can improve the physicochemical properties of pharmaceutical active ingredients, and thus have great potential in improving drug performance. Some studies have obtained the powder spectrum of the co-crystal of flurbiprofen (FBP) and salicylamide (2-OHBZA) but have not obtained a single-crystal structure. In this study, co-crystals of FBP-2-OHBZA with a molar ratio of 1:1 were obtained by slow evaporation using ethyl acetate and tetrahydrofuran for verification. Density functional theory was used to optimize the structure of the hydrogen bond and π−π stacking formed by the co-crystal of FBP and 2-OHBZA. The assay results of the co-crystals of FBP-2-OHBZA are in good agreement with the calculated values reported.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"1 1","pages":"e101 - e108"},"PeriodicalIF":0.0,"publicationDate":"2023-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83155992","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}
Abstract ( R )-Tenofovir phenyl ester (( R ) -1 ) and ( R )-tenofovir diphenyl ester (( R ) -2 ) are key intermediates for the practical synthesis of tenofovir alafenamide fumarate, which is a mainstay antiretroviral for the treatment of chronic hepatitis B and HIV-1 infections. This article deals with the chiral analysis of ( R )- 1 and ( R )- 2 against their respective optical impurity ( S )-tenofovir phenyl ester (( S )- 1 ) and ( S )-tenofovir diphenyl ester (( S )- 2 ) using a polysaccharide-coated chiral stationary phase (CSP) by normal-phase high-performance liquid chromatography (HPLC). To this end, a chiral synthetic strategy for ( S )- 2 was efficiently executed capitalizing on a classical Mitsunobu reaction to stereospecifically invert the configuration of chiral carbon in readily accessible ( R )-HPA (( R )- 4 ) to deliver ( S )-HPA (( S )- 4 ), from which ( S )--tenofovir ((S)- 3 ) was in turn prepared and further transformed into ( S )- 2 . With reference substance ( S )- 2 in hand, a chiral analytical method for ( R )- 2 using Chiralpak AD-H as CSP by normal-phase HPLC has been developed and validated. The validation results indicated that this chiral analytical method has been achieved with satisfactory separation effect, high sensitivity, and good precision and accuracy, and thus can be deployed for the determination of optical impurities in samples of ( R )- 1 (via derivation to ( R )- 2 ) and ( R )- 2 .
{"title":"Chiral Analysis of the Key Intermediates of Tenofovir Alafenamide Fumarate","authors":"Man Li, Ting Zhou, Qing-Wen Zhang","doi":"10.1055/s-0043-1763512","DOIUrl":"https://doi.org/10.1055/s-0043-1763512","url":null,"abstract":"Abstract ( R )-Tenofovir phenyl ester (( R ) -1 ) and ( R )-tenofovir diphenyl ester (( R ) -2 ) are key intermediates for the practical synthesis of tenofovir alafenamide fumarate, which is a mainstay antiretroviral for the treatment of chronic hepatitis B and HIV-1 infections. This article deals with the chiral analysis of ( R )- 1 and ( R )- 2 against their respective optical impurity ( S )-tenofovir phenyl ester (( S )- 1 ) and ( S )-tenofovir diphenyl ester (( S )- 2 ) using a polysaccharide-coated chiral stationary phase (CSP) by normal-phase high-performance liquid chromatography (HPLC). To this end, a chiral synthetic strategy for ( S )- 2 was efficiently executed capitalizing on a classical Mitsunobu reaction to stereospecifically invert the configuration of chiral carbon in readily accessible ( R )-HPA (( R )- 4 ) to deliver ( S )-HPA (( S )- 4 ), from which ( S )--tenofovir ((S)- 3 ) was in turn prepared and further transformed into ( S )- 2 . With reference substance ( S )- 2 in hand, a chiral analytical method for ( R )- 2 using Chiralpak AD-H as CSP by normal-phase HPLC has been developed and validated. The validation results indicated that this chiral analytical method has been achieved with satisfactory separation effect, high sensitivity, and good precision and accuracy, and thus can be deployed for the determination of optical impurities in samples of ( R )- 1 (via derivation to ( R )- 2 ) and ( R )- 2 .","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"11 1","pages":"e38 - e45"},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89013072","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}
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