Pub Date : 2021-04-29DOI: 10.11648/J.JDDMC.20210701.14
Xuliang Wu, Jufeng Li, Yanru Luo, Zhidong Zhang
Objective: To assess effect of PDCA cycle management mode on drug loss in inpatient pharmacy. Methods: From January 2019 to December 2020, we collected the data from hospital work record of inpatient pharmacy each season and data of total drug loss. The valid data of scrap drugs included item name, specification, packing, quantity, wholesale price, expiry date, and scrap reason. In scrap drugs record of hospital, the inpatient pharmacy managers often record drug data from actual situation of inpatient pharmacy and documents from the drug supplier. In addition, we also collected the change of for each season, and compare the result between 2019 and 2020. Result: The results showed that the number of damaged batches reported in 2019 was significantly higher than the number reported in 2020 (122 vs 77), with a difference of 68% between them. Among the drug loss amount, the loss amount increased with the increase of the number of batches reported to be damaged, and the result of loss amount differed by 54%. In quarter records, we observed that most of the losses occurred in the first quarter and the fourth quarter, with monetary losses of around RMB 2,000 in 2020 and about RMB 3,200 in 2019. Compared with 2019 group, there is a lower amount loss (RMB 10,157.88 vs RMB 5515.14) in the amount loss caused by drug loss in 2020, and the annual reported loss in 2020 group is 54% of the annual reported loss in 2019. Further, the dollar loss for each quarter in 2020 group was lower than for each quarter in 2019. Conclusion: PDCA cycle management mode effectively reduced drug broken event, that it provided continuous improvement as the inpatient pharmacy carried out this cycle management.
{"title":"Effect of PDCA Cycle Management Mode on Drug Loss in Inpatient Pharmacy","authors":"Xuliang Wu, Jufeng Li, Yanru Luo, Zhidong Zhang","doi":"10.11648/J.JDDMC.20210701.14","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20210701.14","url":null,"abstract":"Objective: To assess effect of PDCA cycle management mode on drug loss in inpatient pharmacy. Methods: From January 2019 to December 2020, we collected the data from hospital work record of inpatient pharmacy each season and data of total drug loss. The valid data of scrap drugs included item name, specification, packing, quantity, wholesale price, expiry date, and scrap reason. In scrap drugs record of hospital, the inpatient pharmacy managers often record drug data from actual situation of inpatient pharmacy and documents from the drug supplier. In addition, we also collected the change of for each season, and compare the result between 2019 and 2020. Result: The results showed that the number of damaged batches reported in 2019 was significantly higher than the number reported in 2020 (122 vs 77), with a difference of 68% between them. Among the drug loss amount, the loss amount increased with the increase of the number of batches reported to be damaged, and the result of loss amount differed by 54%. In quarter records, we observed that most of the losses occurred in the first quarter and the fourth quarter, with monetary losses of around RMB 2,000 in 2020 and about RMB 3,200 in 2019. Compared with 2019 group, there is a lower amount loss (RMB 10,157.88 vs RMB 5515.14) in the amount loss caused by drug loss in 2020, and the annual reported loss in 2020 group is 54% of the annual reported loss in 2019. Further, the dollar loss for each quarter in 2020 group was lower than for each quarter in 2019. Conclusion: PDCA cycle management mode effectively reduced drug broken event, that it provided continuous improvement as the inpatient pharmacy carried out this cycle management.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75000046","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}
Pub Date : 2021-03-10DOI: 10.11648/J.JDDMC.20210701.12
Javed Ali Lakho, A. Taj, N. A. Rind, S. H. Naqvi
Salvadora oleoides and Withania somnifera are the commonly found plants of Pakistan that are known to possess various medicinal properties. Present study was designed to evaluate the presence of various phytochemicals in these plants both qualitatively and quantitatively. This study was concluded with accessing the antioxidant and antimicrobial potentials of these phytochemicals against E. coli, Shigella Spp, Aspergillus terreus and Aspergillus niger. In addition qualitative analysis of phytochemical constituents i.e. alkaloids, glycosides, flavonoids, saponins, steroids, tannins and terpanoids and quantitative analysis of total proteins, sugars, reducing sugars, phenolics and flavonoids was performed. Plant extracts were also checked for the existence of antioxidant and antimicrobial activities. Results revealed the presence of a wide range of phytoconstituents including alkaloids, glycosides, flavonoids, saponins, steroids, tannins and terpenoids in both the plants. Quantification of few pharmaceutically important phytoconstituents showed the diversified response. Presence of antioxidants was confirmed in S. oleoides (2.14±SD mg/mL) in methanol extracts of leaves and water extract of leaves of W. somnifera (1.97±SD mg/mL). Methanolic extracts of leaves, bark and roots of both the medicinal plants showed inhibitory effects against both fungal and bacterial strains used. Our findings provide strong evidence that these medicinal plants possess phytoconstituents of pharmaceutical importance and thus may serve as an effective alternative to routine therapeutics.
{"title":"Phytochemical Analysis of Salvadora oleoides and Withania somnifera: An Insight into Their Antioxidant and Antimicrobial Capabilities","authors":"Javed Ali Lakho, A. Taj, N. A. Rind, S. H. Naqvi","doi":"10.11648/J.JDDMC.20210701.12","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20210701.12","url":null,"abstract":"Salvadora oleoides and Withania somnifera are the commonly found plants of Pakistan that are known to possess various medicinal properties. Present study was designed to evaluate the presence of various phytochemicals in these plants both qualitatively and quantitatively. This study was concluded with accessing the antioxidant and antimicrobial potentials of these phytochemicals against E. coli, Shigella Spp, Aspergillus terreus and Aspergillus niger. In addition qualitative analysis of phytochemical constituents i.e. alkaloids, glycosides, flavonoids, saponins, steroids, tannins and terpanoids and quantitative analysis of total proteins, sugars, reducing sugars, phenolics and flavonoids was performed. Plant extracts were also checked for the existence of antioxidant and antimicrobial activities. Results revealed the presence of a wide range of phytoconstituents including alkaloids, glycosides, flavonoids, saponins, steroids, tannins and terpenoids in both the plants. Quantification of few pharmaceutically important phytoconstituents showed the diversified response. Presence of antioxidants was confirmed in S. oleoides (2.14±SD mg/mL) in methanol extracts of leaves and water extract of leaves of W. somnifera (1.97±SD mg/mL). Methanolic extracts of leaves, bark and roots of both the medicinal plants showed inhibitory effects against both fungal and bacterial strains used. Our findings provide strong evidence that these medicinal plants possess phytoconstituents of pharmaceutical importance and thus may serve as an effective alternative to routine therapeutics.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79475612","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}
Pub Date : 2021-01-22DOI: 10.11648/J.JDDMC.20210701.11
D. Saadoun, L. Doya, Adnan Dayoub, Oday Jouni
Background: Transient tachypnea of the newborn (TTNB) is a common cause of respiratory distress in late preterm and full-term infants. It is caused by a delay in the clearance of fetal lung fluids. Although TTNB is a self-limited condition, prophylactic antibiotics usually administered for 48-72 hours until negative blood culture is reported. Objective: In this study, we aim to identify the relationship between using prophylactic antibiotics and the duration of tachypnea and hospitalization in neonates with TTNB. Materials and Methods: this was a cohort study design included 102 infants with TTNB. The infants were divided into two groups, one received supportive care, and the other received supportive care with intravenous antibiotics. The clinical signs and laboratory results were examined in the two groups. Results: Of total 102 infants who were included in this study, 41 (40.2%) were received supportive care with prophylactic intravenous antibiotics. There were no significant differences between two groups in terms of gender, gestational age, birth weight, mode of delivery, and white blood cell. A significant relation was found between receiving prophylactic antibiotics with the duration of tachypnea and hospitalization. Conclusions: In the recent study, we found an increase in the hospitalization and tachypnea period in the group received antibiotics.
{"title":"Transient Tachypnea of the Newborn and the Use of Prophylactic Antibiotics","authors":"D. Saadoun, L. Doya, Adnan Dayoub, Oday Jouni","doi":"10.11648/J.JDDMC.20210701.11","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20210701.11","url":null,"abstract":"Background: Transient tachypnea of the newborn (TTNB) is a common cause of respiratory distress in late preterm and full-term infants. It is caused by a delay in the clearance of fetal lung fluids. Although TTNB is a self-limited condition, prophylactic antibiotics usually administered for 48-72 hours until negative blood culture is reported. Objective: In this study, we aim to identify the relationship between using prophylactic antibiotics and the duration of tachypnea and hospitalization in neonates with TTNB. Materials and Methods: this was a cohort study design included 102 infants with TTNB. The infants were divided into two groups, one received supportive care, and the other received supportive care with intravenous antibiotics. The clinical signs and laboratory results were examined in the two groups. Results: Of total 102 infants who were included in this study, 41 (40.2%) were received supportive care with prophylactic intravenous antibiotics. There were no significant differences between two groups in terms of gender, gestational age, birth weight, mode of delivery, and white blood cell. A significant relation was found between receiving prophylactic antibiotics with the duration of tachypnea and hospitalization. Conclusions: In the recent study, we found an increase in the hospitalization and tachypnea period in the group received antibiotics.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72663040","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 design and evaluation of antimicrobial activities of an isonitrosomalononitrile silver(I) salt was reported. This highly stable water-soluble silver salt shows Minimum Inhibitory Concentrations (MIC) values ranging from 0.15 to 5 µg/mL towards both sensitive and resistant Gram-positive and negative bacteria. Furthermore, this silver salt has been investigated for its ability to treat a S. aureus infected Galleria mellonella larvae animal model with promising results. Thus, our results demonstrated that 80% of the treated larvae survived after 24h with respect to 10% of the untreated ones, respectively.
{"title":"Assessment of in vitro and in vivo Antimicrobial Activity of an Isonitrosomalononitrile Silver(I) Salt","authors":"Colmont M, Brunel Jm","doi":"10.16966/2578-9589.117","DOIUrl":"https://doi.org/10.16966/2578-9589.117","url":null,"abstract":"The design and evaluation of antimicrobial activities of an isonitrosomalononitrile silver(I) salt was reported. This highly stable water-soluble silver salt shows Minimum Inhibitory Concentrations (MIC) values ranging from 0.15 to 5 µg/mL towards both sensitive and resistant Gram-positive and negative bacteria. Furthermore, this silver salt has been investigated for its ability to treat a S. aureus infected Galleria mellonella larvae animal model with promising results. Thus, our results demonstrated that 80% of the treated larvae survived after 24h with respect to 10% of the untreated ones, respectively.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"178 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85840289","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}
We designed de novo and synthesized two series of five 26-residue amphipathic α-helical cationic antimicrobial peptides (AMPs) with five or six positively charged residues (D-Lys, L-Dab (2,4-diaminobutyric acid) or L-Dap (2,3-diaminopropionic acid)) on the polar face where all other residues are in the D-conformation. Hemolytic activity against human red blood cells was determined using the most stringent conditions for the hemolysis assay, 18h at 37°C, 1% human erythrocytes and peptide concentrations up to 1000 μg/mL (~380 μM). Antimicrobial activity was determined against 7 Acinetobacter baumannii strains, resistant to polymyxin B and colistin (antibiotics of last resort) to show the effect of positively charged residues in two different locations on the polar face (positions 3, 7, 11, 18, 22 and 26 versus positions 3, 7, 14, 15, 22 and 26). All 10 peptides had two D-Lys residues in the center of the non-polar face as “specificity determinants” at positions 13 and 16 which provide specificity for prokaryotic cells over eukaryotic cells. Specificity determinants also maintain excellent antimicrobial activity in the presence of human sera. This study shows that the location and type of positively charged residue (Dab and Dap) on the polar face are critical to obtain the best therapeutic indices.
{"title":"Design of Novel Amphipathic α-Helical Antimicrobial Peptides with No Toxicity as Therapeutics against the Antibiotic-Resistant Gram-Negative Bacterial Pathogen, Acinetobacter Baumannii","authors":"Mant Ct, J. Z, G. L, D. T, Hodges Rs","doi":"10.16966/2578-9589.114","DOIUrl":"https://doi.org/10.16966/2578-9589.114","url":null,"abstract":"We designed de novo and synthesized two series of five 26-residue amphipathic α-helical cationic antimicrobial peptides (AMPs) with five or six positively charged residues (D-Lys, L-Dab (2,4-diaminobutyric acid) or L-Dap (2,3-diaminopropionic acid)) on the polar face where all other residues are in the D-conformation. Hemolytic activity against human red blood cells was determined using the most stringent conditions for the hemolysis assay, 18h at 37°C, 1% human erythrocytes and peptide concentrations up to 1000 μg/mL (~380 μM). Antimicrobial activity was determined against 7 Acinetobacter baumannii strains, resistant to polymyxin B and colistin (antibiotics of last resort) to show the effect of positively charged residues in two different locations on the polar face (positions 3, 7, 11, 18, 22 and 26 versus positions 3, 7, 14, 15, 22 and 26). All 10 peptides had two D-Lys residues in the center of the non-polar face as “specificity determinants” at positions 13 and 16 which provide specificity for prokaryotic cells over eukaryotic cells. Specificity determinants also maintain excellent antimicrobial activity in the presence of human sera. This study shows that the location and type of positively charged residue (Dab and Dap) on the polar face are critical to obtain the best therapeutic indices.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"146 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77719360","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}
Pub Date : 2019-12-23DOI: 10.11648/J.JDDMC.20190504.11
S. Ho, Yili Lin, Sheng-Fa Tsai, Shoei‐Sheng Lee
The type A proanthocyanidins (2−8) with (2β→O→7, 4β→8) interflavane linkage, isolated from Machilus philippinensis, have been found to possess inhibitory activity against α-glucosidase (EC 3.2.1.20 from Bacillus stearothermophilus). To rationalize such activity, computer assisted docking of these compounds and the positive control, acarbose, on the conformation model of α-glucosidase (AG), built by using human intestinal maltase glucoamylase as a template, was undertaken in this study. The result showed good correlation between IC50 values and docking scores, expressed as binding energy (ΔG), obtained from London (trimatch)-refinement (forcefield AffinityΔG) mode. Among these isolates, the most potent aesculitannin B (2) (IC50 3.5μM) showed the best docking score (ΔG -21.48 kcal/mol). Being interested in clarification of structure and activity relationship, virtual screening on the related compounds, including the de-unit III homologs of 2−8 (i.e., nor- series) and additional 13 stereoisomers of the trimeric 2 at the C-2 and C-3 positions of units II and III, was further carried out. This docking study indicated the de-unit III homologs of 2−8 did not have better binding energies than 2. As for the trimers, 3-entC, 3C-entE, 3ent-C, 3C, and 3ent, showed comparable docking score to 2. The verification of this virtual screening was partially done by evaluating the inhibitory activity of the dimeric 2-nor-ent, 3-nor, 3-nor-ent, and iso-2-nor-ent, isolated from peanut skins, against α-glucosidase. Of these, iso-2-nor-ent, the only proanthocyanidin with (2β→O→7, 4β→6) interflavane linkage, showed the best activity (IC50 9.72 μM). Their simulation profiles of docking score also displayed a reasonable qualitative consistency with the overall trend of the bioassay results. This study demonstrates that virtual screening using this built model to search α-glucosidase inhibitors is facile and feasible and peanut skin might be used as a hypoglycemic food.
{"title":"In Silico Docking Analysis of A-type Proanthocyanidins to α-Glucosidase Constructed by Correlation with in Vitro Bioassay","authors":"S. Ho, Yili Lin, Sheng-Fa Tsai, Shoei‐Sheng Lee","doi":"10.11648/J.JDDMC.20190504.11","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20190504.11","url":null,"abstract":"The type A proanthocyanidins (2−8) with (2β→O→7, 4β→8) interflavane linkage, isolated from Machilus philippinensis, have been found to possess inhibitory activity against α-glucosidase (EC 3.2.1.20 from Bacillus stearothermophilus). To rationalize such activity, computer assisted docking of these compounds and the positive control, acarbose, on the conformation model of α-glucosidase (AG), built by using human intestinal maltase glucoamylase as a template, was undertaken in this study. The result showed good correlation between IC50 values and docking scores, expressed as binding energy (ΔG), obtained from London (trimatch)-refinement (forcefield AffinityΔG) mode. Among these isolates, the most potent aesculitannin B (2) (IC50 3.5μM) showed the best docking score (ΔG -21.48 kcal/mol). Being interested in clarification of structure and activity relationship, virtual screening on the related compounds, including the de-unit III homologs of 2−8 (i.e., nor- series) and additional 13 stereoisomers of the trimeric 2 at the C-2 and C-3 positions of units II and III, was further carried out. This docking study indicated the de-unit III homologs of 2−8 did not have better binding energies than 2. As for the trimers, 3-entC, 3C-entE, 3ent-C, 3C, and 3ent, showed comparable docking score to 2. The verification of this virtual screening was partially done by evaluating the inhibitory activity of the dimeric 2-nor-ent, 3-nor, 3-nor-ent, and iso-2-nor-ent, isolated from peanut skins, against α-glucosidase. Of these, iso-2-nor-ent, the only proanthocyanidin with (2β→O→7, 4β→6) interflavane linkage, showed the best activity (IC50 9.72 μM). Their simulation profiles of docking score also displayed a reasonable qualitative consistency with the overall trend of the bioassay results. This study demonstrates that virtual screening using this built model to search α-glucosidase inhibitors is facile and feasible and peanut skin might be used as a hypoglycemic food.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78520050","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}
Pub Date : 2019-09-02DOI: 10.11648/J.JDDMC.20190503.12
João Antunes, Michelle Bueno de Moura Pereira
The development of new drugs can present several problems, it is a important obstacle the ability to adapt a molecule that is a potent pharmacological inhibitor and that is also possible to execute its synthesis. Quinazolines are known to be capable of inhibiting kinases. Thus, a detailed study was carried out to propose new quinazolines with already known synthetic routes, and that were promising for the ability to inhibit kinases. A drug candidate molecule shall be proposed to have a good absorption, an extensive distribution so it’s capable of reaching the desired therapeutic targets. Lipinski's Rule of 5 in computational studies has been applied to select more promising molecules. In this study, the molecules proposed for the synthesis were systematically designed in appropriate computational programs to test several substituents of the quinazoline nucleus on the capacity of these molecules to be considered inhibitors of kinases. Six molecules were selected with the best results to inhibit kinases. In the study to evaluate the variation of substituents, the result obtained for the 8-position of the quinazoline ring and with the -Cl substituent at that ring position presented 60% of the 10 best molecules capable of inhibiting kinases. The molecular docking study confirmed that the two most promising molecules to inhibit kinase also obtained the best results to inhibit AKT kinase. Therefore, through this study it was possible to select six more promising molecules to be synthesized and available in large screening tests for several therapeutic targets known as High-Throughput Screening.
{"title":"Rational Computational Study for New Kinase Inhibitors","authors":"João Antunes, Michelle Bueno de Moura Pereira","doi":"10.11648/J.JDDMC.20190503.12","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20190503.12","url":null,"abstract":"The development of new drugs can present several problems, it is a important obstacle the ability to adapt a molecule that is a potent pharmacological inhibitor and that is also possible to execute its synthesis. Quinazolines are known to be capable of inhibiting kinases. Thus, a detailed study was carried out to propose new quinazolines with already known synthetic routes, and that were promising for the ability to inhibit kinases. A drug candidate molecule shall be proposed to have a good absorption, an extensive distribution so it’s capable of reaching the desired therapeutic targets. Lipinski's Rule of 5 in computational studies has been applied to select more promising molecules. In this study, the molecules proposed for the synthesis were systematically designed in appropriate computational programs to test several substituents of the quinazoline nucleus on the capacity of these molecules to be considered inhibitors of kinases. Six molecules were selected with the best results to inhibit kinases. In the study to evaluate the variation of substituents, the result obtained for the 8-position of the quinazoline ring and with the -Cl substituent at that ring position presented 60% of the 10 best molecules capable of inhibiting kinases. The molecular docking study confirmed that the two most promising molecules to inhibit kinase also obtained the best results to inhibit AKT kinase. Therefore, through this study it was possible to select six more promising molecules to be synthesized and available in large screening tests for several therapeutic targets known as High-Throughput Screening.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73392533","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}
Pub Date : 2019-08-23DOI: 10.11648/J.JDDMC.20190503.11
N. Takada, T. Okada, E. Kogawa, Y. Sanada, A. Ishidoya
Hypertension is currently one of the most serious health issues worldwide. Nicotianamine, a non-peptide-type amino acid trimer, is ubiquitously present in higher plants and plays a role as an internal metal transporter. It is known that nicotianamine inhibits ACE activity and that oral treatment with the compound improves hypertension. However the mode of action remains unclear, due to lack of crystallographic data. Although a structure-activity relationship study of nicotianamine has the potential to uncover the details of the inhibition profile, the azetidine-2-carboxylic acid moiety in nicotianamine has become a critical barrier for further biochemical research due to limited commercial supply and difficulties with structural modification. In this paper, ten nicotianamine analogs without azetidine-2-carboxylic acid moiety were prepared and their inhibition of angiotensin I-converting enzyme was investigated. Among these analogs, a phenylalanine analog, (2S,3′S,3″S)-N-{3′-(3″-amino-3″-carboxypropylamino)-3′-carboxypropyl}phenylalanine, displayed the most potent activity. The inhibition activity of the compound corresponded to that of captopril. These results suggested a possibility of structural modification of nicotianamie to develop antihypertensive drugs. Molecular docking studies with Gold were also performed to predict the binding poses of nicotianamine and its analog, suggesting that nicotianamine and its analogs combine a plausible allosteric site in an area away from the catalytic site in ACE.
高血压是目前世界范围内最严重的健康问题之一。烟胺是一种非肽型氨基酸三聚体，普遍存在于高等植物中，起着内部金属转运体的作用。众所周知，烟胺可抑制ACE活性，口服该化合物可改善高血压。然而，由于缺乏晶体学数据，其作用模式尚不清楚。尽管对烟胺的构效关系研究有可能揭示其抑制谱的细节，但由于商业供应有限和结构修饰困难，烟胺中的氮杂丁-2-羧酸片段已成为进一步生化研究的关键障碍。本文制备了10种不含氮杂啶-2-羧酸片段的烟胺类似物，并研究了它们对血管紧张素i转换酶的抑制作用。在这些类似物中，苯丙氨酸类似物(2S, 3s,3″S)- n -{3 ' -(3″-氨基-3″-羧基丙基氨基)-3 ' -羧基丙基}苯丙氨酸表现出最强的活性。该化合物的抑制活性与卡托普利相当。这些结果提示了对烟胺进行结构修饰以开发抗高血压药物的可能性。与Gold的分子对接研究也用于预测烟胺及其类似物的结合姿态，表明烟胺及其类似物在ACE中远离催化位点的区域结合了一个似是而非的变构位点。
{"title":"New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program","authors":"N. Takada, T. Okada, E. Kogawa, Y. Sanada, A. Ishidoya","doi":"10.11648/J.JDDMC.20190503.11","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20190503.11","url":null,"abstract":"Hypertension is currently one of the most serious health issues worldwide. Nicotianamine, a non-peptide-type amino acid trimer, is ubiquitously present in higher plants and plays a role as an internal metal transporter. It is known that nicotianamine inhibits ACE activity and that oral treatment with the compound improves hypertension. However the mode of action remains unclear, due to lack of crystallographic data. Although a structure-activity relationship study of nicotianamine has the potential to uncover the details of the inhibition profile, the azetidine-2-carboxylic acid moiety in nicotianamine has become a critical barrier for further biochemical research due to limited commercial supply and difficulties with structural modification. In this paper, ten nicotianamine analogs without azetidine-2-carboxylic acid moiety were prepared and their inhibition of angiotensin I-converting enzyme was investigated. Among these analogs, a phenylalanine analog, (2S,3′S,3″S)-N-{3′-(3″-amino-3″-carboxypropylamino)-3′-carboxypropyl}phenylalanine, displayed the most potent activity. The inhibition activity of the compound corresponded to that of captopril. These results suggested a possibility of structural modification of nicotianamie to develop antihypertensive drugs. Molecular docking studies with Gold were also performed to predict the binding poses of nicotianamine and its analog, suggesting that nicotianamine and its analogs combine a plausible allosteric site in an area away from the catalytic site in ACE.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76292252","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}
Pub Date : 2019-08-07DOI: 10.11648/J.JDDMC.20190502.12
Ortega Leticia, G. Martin, D. Rodríguez
The purpose of this work is to improve one of the important physicochemical properties of an active pharmaceutical ingredient (API), as is the water solubility of paracetamol. To improve the physicochemical properties of this API, two pharmaceutical excipients such as the HPMC and maltodextrin were used, which help to improve the solubility, and this helps to the manufacturing process of a pharmaceutical product. Different granule formulations were manufactured by applying a matrix design of experiment where the wet granulation process was performed, combining Paracetamol with the excipients to obtain a uniform particle size and subsequently evaluate the properties of interest. The solubility was evaluated using a method (Mexican pharmacopoeia - FEUM) based on UV / VIS method, performing the calibration curve only for the API to evaluate the granule and calculate the percentage of solubility of these. Favorable results were obtained for two of the seven granule formulations manufactured, the mixture of granule F and G: 25 g of paracetamol, 1.5; 1.75 g of HPMC and 23.5 g; 23.25 of the maltodextrin has a solubility of 104.17% and 101.48% of the G, which shows that the process by wet granulation can improve its solubility. This type of co-processed granule also fulfills the function of masking the bitter taste of paracetamol in one oral pharmaceutical form, as in the case of a syrup and it could be an advantage in the market. The flavor was evaluated by a panel of 20 people and the taste of the syrups that were prepared with the granule with better solubility was compared with the syrups containing only the API dissolved. It is shown that the granules F have improvement in the solubility of paracetamol and can mask the unpleasant (bitter) taste of the active ingredient.
这项工作的目的是改善活性药物成分(API)的一个重要的物理化学性质，即扑热息痛的水溶性。为了改善该原料药的理化性质，使用了两种药用辅料，如HPMC和麦芽糖糊精，这有助于提高溶解度，这有助于制药产品的制造过程。不同的颗粒配方是通过应用实验的基质设计，其中湿制粒过程进行，结合扑热息痛与辅料，以获得一个统一的粒度，随后评估感兴趣的性质。采用基于紫外/可见法的方法(墨西哥药典- FEUM)评价溶解度，仅对API进行校准曲线评价颗粒并计算其溶解度百分比。制备的七种颗粒剂中有两种效果良好，F和G颗粒剂的混合物:25g扑热息痛，1.5;1.75 g HPMC和23.5 g;23.25的麦芽糖糊精对G的溶解度为104.17%，对G的溶解度为101.48%，说明湿造粒工艺可以提高其溶解度。这种类型的协同加工颗粒还可以在一种口服药物形式中掩盖扑热息痛的苦味，就像糖浆一样，这可能是市场上的一个优势。由20人组成的小组对风味进行了评估，并用溶解度更好的颗粒制备的糖浆的味道与仅溶解API的糖浆进行了比较。研究表明，颗粒F改善了扑热息痛的溶解度，可以掩盖活性成分的不愉快(苦)味。
{"title":"Development of Co-processed Paracetamol with Hydroxypropyl Methylcellulose (HPMC) and Maltodextrin by Wet Granulation Process","authors":"Ortega Leticia, G. Martin, D. Rodríguez","doi":"10.11648/J.JDDMC.20190502.12","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20190502.12","url":null,"abstract":"The purpose of this work is to improve one of the important physicochemical properties of an active pharmaceutical ingredient (API), as is the water solubility of paracetamol. To improve the physicochemical properties of this API, two pharmaceutical excipients such as the HPMC and maltodextrin were used, which help to improve the solubility, and this helps to the manufacturing process of a pharmaceutical product. Different granule formulations were manufactured by applying a matrix design of experiment where the wet granulation process was performed, combining Paracetamol with the excipients to obtain a uniform particle size and subsequently evaluate the properties of interest. The solubility was evaluated using a method (Mexican pharmacopoeia - FEUM) based on UV / VIS method, performing the calibration curve only for the API to evaluate the granule and calculate the percentage of solubility of these. Favorable results were obtained for two of the seven granule formulations manufactured, the mixture of granule F and G: 25 g of paracetamol, 1.5; 1.75 g of HPMC and 23.5 g; 23.25 of the maltodextrin has a solubility of 104.17% and 101.48% of the G, which shows that the process by wet granulation can improve its solubility. This type of co-processed granule also fulfills the function of masking the bitter taste of paracetamol in one oral pharmaceutical form, as in the case of a syrup and it could be an advantage in the market. The flavor was evaluated by a panel of 20 people and the taste of the syrups that were prepared with the granule with better solubility was compared with the syrups containing only the API dissolved. It is shown that the granules F have improvement in the solubility of paracetamol and can mask the unpleasant (bitter) taste of the active ingredient.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76962746","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}
Pub Date : 2019-08-07DOI: 10.11648/J.JDDMC.20190502.11
Meghdad Payab, M. Chaichi, Omeleila Nazari, F. Maleki
In this study, tannins were extracted by two methods (soaking and Soxhlet) with three different solvents (water, methanol and aqueous methanol 50%) and the three kind plant (walnut shell, gall oak and walnut leaves), that the highest extraction efficiency (82.08%) was related to extraction with aqueous methanol by Soxhlet method from the oak galls. Although the results of soaking were nearly to the Soxhlet. One oak Gall extract was evaluated by Lowenthal method that the result was showed that reducing materials such as tannins are 26.14%. The extracted was evaluated by Folin-Ciocalteu method that suggests phenolic compounds in the extract was 15.27, (61.07± 7.12 mg compared to gallic acid). Result of evaluation of antioxidant activity of the extracted showed the high antioxidant properties of tannins compared to ascorbic acid at less than 100 ppm concentrations, but these properties comparable to ascorbic acid of the higher concentrations, so a lower dose of the extract was may be helpful. The chelation properties of the iron ions at low concentrations of iron (III), oak was showed better performance compared to Deferoxamine but Deferoxamine due to complex formation with higher stoichiometry (1: 6) at high concentrations of Fe (III), has performed better than the oak.
{"title":"Tannin Extraction from Oak Gall and Evaluation of Anti-Oxidant Activity and Tannin Iron Chelation Compared with Deferoxamine Drug","authors":"Meghdad Payab, M. Chaichi, Omeleila Nazari, F. Maleki","doi":"10.11648/J.JDDMC.20190502.11","DOIUrl":"https://doi.org/10.11648/J.JDDMC.20190502.11","url":null,"abstract":"In this study, tannins were extracted by two methods (soaking and Soxhlet) with three different solvents (water, methanol and aqueous methanol 50%) and the three kind plant (walnut shell, gall oak and walnut leaves), that the highest extraction efficiency (82.08%) was related to extraction with aqueous methanol by Soxhlet method from the oak galls. Although the results of soaking were nearly to the Soxhlet. One oak Gall extract was evaluated by Lowenthal method that the result was showed that reducing materials such as tannins are 26.14%. The extracted was evaluated by Folin-Ciocalteu method that suggests phenolic compounds in the extract was 15.27, (61.07± 7.12 mg compared to gallic acid). Result of evaluation of antioxidant activity of the extracted showed the high antioxidant properties of tannins compared to ascorbic acid at less than 100 ppm concentrations, but these properties comparable to ascorbic acid of the higher concentrations, so a lower dose of the extract was may be helpful. The chelation properties of the iron ions at low concentrations of iron (III), oak was showed better performance compared to Deferoxamine but Deferoxamine due to complex formation with higher stoichiometry (1: 6) at high concentrations of Fe (III), has performed better than the oak.","PeriodicalId":16581,"journal":{"name":"Journal of Medicinal Chemistry and Drug Design","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90773902","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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