Pub Date : 2024-01-10DOI: 10.3897/pharmacia.71.e112503
Iman Hamdan
The skin offers a route of administration with numerous advantages. However, one of the major limitations of this route is the limited number of drugs that possess the ideal physicochemical properties to passively diffuse through the skin barrier. Today, microneedle (MN) technology proved to be superior in the field of drug delivery. MN arrays are devices that consist of micron-sized projections which pierce the stratum corneum (SC), the main barrier for drug delivery across the skin. MN technology has the potential to provide a localised drug delivery with minimal toxicity and expand the range of drugs for transdermal and intradermal delivery. In this comprehensive review, MN technology was thoroughly discussed. Meeting regulatory standards and large-scale production is essential to advance MN technology into a cost-effectiveness commercial scale.
{"title":"Microneedle and drug delivery across the skin: An overview","authors":"Iman Hamdan","doi":"10.3897/pharmacia.71.e112503","DOIUrl":"https://doi.org/10.3897/pharmacia.71.e112503","url":null,"abstract":"The skin offers a route of administration with numerous advantages. However, one of the major limitations of this route is the limited number of drugs that possess the ideal physicochemical properties to passively diffuse through the skin barrier. Today, microneedle (MN) technology proved to be superior in the field of drug delivery. MN arrays are devices that consist of micron-sized projections which pierce the stratum corneum (SC), the main barrier for drug delivery across the skin. MN technology has the potential to provide a localised drug delivery with minimal toxicity and expand the range of drugs for transdermal and intradermal delivery. In this comprehensive review, MN technology was thoroughly discussed. Meeting regulatory standards and large-scale production is essential to advance MN technology into a cost-effectiveness commercial scale.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"69 14","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139440795","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 : 2024-01-09DOI: 10.3897/pharmacia.71.e113659
Raheeq Khairy Abdullah, Reem A. Issa, M. Abu-Samak, Beisan A. Mohammad, M. Abbas, S. Awwad
Diabetes is a widespread health issue that impacts people all over the globe. The Equisetum ramosissimum L. plant has numerous traditional uses and pharmacological properties, including antidiabetic effects.The objective of this study was to thoroughly examine the advantages of incorporating extracts from the aerial components of E. ramosissimum to control diabetic nephropathy. The phytochemical constituents of E. ramosissimum extract were explored using phytochemical and HPLC analysis, focusing on phenols and flavonoid content. The effect of plant extract was evaluated on different kidney function parameters linked to diabetic nephropathy (fasting blood glucose, creatinine, uric acid, and urea) in streptozotocin induced-diabetic rats. Histopathological changes in the liver were also examined. The results showed methanol and ethanol extracts of E. ramosissimum have a total content of phenols (equivalent to gallic acid, 7.62 and 8.97 mg/g) and flavonoids (equivalent to quercetin, 8.87 and 12.86 mg/g), respectively. After conducting the UHPLC-MS/MS analysis, it was found that both the methanol and ethanol extracts contained isoferulic acid, ISO-Orientin, myristic acid, linoelaidic acid, rutin, and 3-Glu-7-Rha quercetin. Additionally, isoferulic acid, myristic acid, linoelaidic acid, rutin, and 3-Glu-7-Rha quercetin were present in the extracts. The ethanol extract of E. ramosissimum significantly impacted STZ-induced diabetic mice by reducing their fasting blood glucose levels, and their creatinine and urea levels (P < 0.005). In conclusion, E. ramosissimum ethanol extract has shown potential effects to counteract some diabetes consequences on kidney function. Therefore, further studies are required to investigate its effect on other diabetes-related complications.
{"title":"Nephroprotective effects of Equisetum ramosissimum L. extract in streptozotocin-induced diabetic rats","authors":"Raheeq Khairy Abdullah, Reem A. Issa, M. Abu-Samak, Beisan A. Mohammad, M. Abbas, S. Awwad","doi":"10.3897/pharmacia.71.e113659","DOIUrl":"https://doi.org/10.3897/pharmacia.71.e113659","url":null,"abstract":"Diabetes is a widespread health issue that impacts people all over the globe. The Equisetum ramosissimum L. plant has numerous traditional uses and pharmacological properties, including antidiabetic effects.The objective of this study was to thoroughly examine the advantages of incorporating extracts from the aerial components of E. ramosissimum to control diabetic nephropathy. The phytochemical constituents of E. ramosissimum extract were explored using phytochemical and HPLC analysis, focusing on phenols and flavonoid content. The effect of plant extract was evaluated on different kidney function parameters linked to diabetic nephropathy (fasting blood glucose, creatinine, uric acid, and urea) in streptozotocin induced-diabetic rats. Histopathological changes in the liver were also examined. The results showed methanol and ethanol extracts of E. ramosissimum have a total content of phenols (equivalent to gallic acid, 7.62 and 8.97 mg/g) and flavonoids (equivalent to quercetin, 8.87 and 12.86 mg/g), respectively. After conducting the UHPLC-MS/MS analysis, it was found that both the methanol and ethanol extracts contained isoferulic acid, ISO-Orientin, myristic acid, linoelaidic acid, rutin, and 3-Glu-7-Rha quercetin. Additionally, isoferulic acid, myristic acid, linoelaidic acid, rutin, and 3-Glu-7-Rha quercetin were present in the extracts. The ethanol extract of E. ramosissimum significantly impacted STZ-induced diabetic mice by reducing their fasting blood glucose levels, and their creatinine and urea levels (P < 0.005). In conclusion, E. ramosissimum ethanol extract has shown potential effects to counteract some diabetes consequences on kidney function. Therefore, further studies are required to investigate its effect on other diabetes-related complications.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"21 8","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441417","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 : 2024-01-09DOI: 10.3897/pharmacia.71.e112385
S. Abarova, Katerina Stoitchkova, Svetlin Tzonev, Maria Argirova, D. Yancheva, N. Anastassova, Boris Tenchov
In the present work we studied the interactions of a newly synthesized drug candidate, 2-(2-hydroxy-4-methoxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine (2H4MBBH), with human serum albumin (HSA) by fluorescence spectroscopy. 2H4MBBH-HSA binding parameters were assessed by fluorescence quenching strategy. As made clear by the concentration data, 2H4MBBH unequivocally quenched the instrinsic HSA fluorescence. The calculated Stern-Volmer quenching constant Ksv, the Ka of 2H4MBBH-HSA complexes, as well as the thermodynamic parameters ∆H°, ∆S° and ∆G°, showed that the H-bonding forces play major part in the interaction of 2H4MBBH with HSA. These calculations point to a quenching component based on 2H4MBBH-HSA static complex formation rather than energetic collisions.
{"title":"Spectroscopic and thermodynamic characterization of the interaction of a new synthesized antitumor drug candidate 2H4MBBH with human serum albumin","authors":"S. Abarova, Katerina Stoitchkova, Svetlin Tzonev, Maria Argirova, D. Yancheva, N. Anastassova, Boris Tenchov","doi":"10.3897/pharmacia.71.e112385","DOIUrl":"https://doi.org/10.3897/pharmacia.71.e112385","url":null,"abstract":"In the present work we studied the interactions of a newly synthesized drug candidate, 2-(2-hydroxy-4-methoxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine (2H4MBBH), with human serum albumin (HSA) by fluorescence spectroscopy.\u0000 2H4MBBH-HSA binding parameters were assessed by fluorescence quenching strategy. As made clear by the concentration data, 2H4MBBH unequivocally quenched the instrinsic HSA fluorescence. The calculated Stern-Volmer quenching constant Ksv, the Ka of 2H4MBBH-HSA complexes, as well as the thermodynamic parameters ∆H°, ∆S° and ∆G°, showed that the H-bonding forces play major part in the interaction of 2H4MBBH with HSA. These calculations point to a quenching component based on 2H4MBBH-HSA static complex formation rather than energetic collisions.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"2 2","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441427","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 : 2024-01-04DOI: 10.3897/pharmacia.71.e115504
Iveta Nedeva, V. Vodenicharov, V. Karamfilova, Y. Assyov
Background: Parathyroid cysts are rare entities. They account for less than 0.5% of parathyroid lesions. They are divided into two main groups: functioning and non-functioning. Case description: We present a 36- year-old woman with complaints of palpitations, sweating, and nervousness of about 2 months’ duration. From an ultrasound of the thyroid gland with data on anechoic formation under the lower pole of the left lobe of the thyroid gland with dimension 14/16/24 mm. Fine needle aspiration (FNA) of the formation was performed with aspiration of about 5 ml of clear liquid and examination of washout. PTH from the washout of the extrathyroidal lesion-1040 pg/ml. A month later with ultrasound data on recurrence of the formation; repeated aspiration of about 5 ml of blood fluid was performed with subsequent application of 1 ml of absolute alcohol intranodal. Conclusion: Thirty days after the procedure with ultrasound data of slight regression in the dimension: 10/11/20 mm.
{"title":"A 36-year-old woman with a parathyroid cyst","authors":"Iveta Nedeva, V. Vodenicharov, V. Karamfilova, Y. Assyov","doi":"10.3897/pharmacia.71.e115504","DOIUrl":"https://doi.org/10.3897/pharmacia.71.e115504","url":null,"abstract":"Background: Parathyroid cysts are rare entities. They account for less than 0.5% of parathyroid lesions. They are divided into two main groups: functioning and non-functioning.\u0000 Case description: We present a 36- year-old woman with complaints of palpitations, sweating, and nervousness of about 2 months’ duration. From an ultrasound of the thyroid gland with data on anechoic formation under the lower pole of the left lobe of the thyroid gland with dimension 14/16/24 mm. Fine needle aspiration (FNA) of the formation was performed with aspiration of about 5 ml of clear liquid and examination of washout. PTH from the washout of the extrathyroidal lesion-1040 pg/ml. A month later with ultrasound data on recurrence of the formation; repeated aspiration of about 5 ml of blood fluid was performed with subsequent application of 1 ml of absolute alcohol intranodal.\u0000 Conclusion: Thirty days after the procedure with ultrasound data of slight regression in the dimension: 10/11/20 mm.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"35 8","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386396","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 : 2024-01-04DOI: 10.3897/pharmacia.71.e106817
W. Nafisah, Annia Zhafarina Dalilati, Y. Christina, Mochammad Fitri Atho'illah, Muhaimin Rifa’ia, T. Noor, Alexander Patera Nugraha
Coffee is a kind of daily beverage, and its correlation with cardiovascular disease and atherosclerosis is still debatable. The aim of this study is to investigate the effects of Amstirdam coffee extract (ACE) on lipoprotein-associated phospholipase A2 (Lp-PLA2) and the inflammatory response in atherosclerosis mouse models. The study used 25 Swiss male mice for five groups (n = 5): healthy mice fed a normal diet (N); mice fed a high-fat, high-fructose diet (HFFD); mice fed HFFD and treated with ACE at doses of 104 (D1), 520 (D2), and 5200 mg/kg BW (D3). The levels of Lp-PLA2, regulatory T cells (Tregs) (CD4+CD25+CD62L+, CD4+CD25+IL-10+, CD4+CD25+TGF-+), IL-10 (CD4+IL-10+), and TGF-B (CD4+TGF+) were analyzed using a flow cytometer. Histological analysis of the mouse aorta was done by hematoxylin and eosin (HE) staining. This study indicated a significant increase in total cholesterol (TC), triglyceride (TG), LDL, and Lp-PLA2 levels in the HFFD group. HFFD also reduced HDL, IL-10, and TGF produced by CD4 and Tregs compared with the normal group. ACE at all doses significantly reduced Lp-PLA2 levels compared with the HFFD group (p < 0.05). Interestingly, the administration of 520 mg/kg BW ACE (D2) increased the production of IL-10 significantly compared to other doses (p < 0.05). The D3 group possessed a high TGF- production and Treg expression level significantly different between groups (p < 0.05). Foam cells were mostly found in the aorta of the HFFD group compared to the normal and ACE treatment groups. This study suggested that ACE could reduce Lp-PLA2 enzyme activity and foam cell formation through the immunosuppressive activity of IL-10 and TGF cytokines.
{"title":"Amstirdam coffee ameliorates Lp-PLA2 and the inflammatory response in an atherosclerosis rats","authors":"W. Nafisah, Annia Zhafarina Dalilati, Y. Christina, Mochammad Fitri Atho'illah, Muhaimin Rifa’ia, T. Noor, Alexander Patera Nugraha","doi":"10.3897/pharmacia.71.e106817","DOIUrl":"https://doi.org/10.3897/pharmacia.71.e106817","url":null,"abstract":"Coffee is a kind of daily beverage, and its correlation with cardiovascular disease and atherosclerosis is still debatable. The aim of this study is to investigate the effects of Amstirdam coffee extract (ACE) on lipoprotein-associated phospholipase A2 (Lp-PLA2) and the inflammatory response in atherosclerosis mouse models. The study used 25 Swiss male mice for five groups (n = 5): healthy mice fed a normal diet (N); mice fed a high-fat, high-fructose diet (HFFD); mice fed HFFD and treated with ACE at doses of 104 (D1), 520 (D2), and 5200 mg/kg BW (D3). The levels of Lp-PLA2, regulatory T cells (Tregs) (CD4+CD25+CD62L+, CD4+CD25+IL-10+, CD4+CD25+TGF-+), IL-10 (CD4+IL-10+), and TGF-B (CD4+TGF+) were analyzed using a flow cytometer. Histological analysis of the mouse aorta was done by hematoxylin and eosin (HE) staining. This study indicated a significant increase in total cholesterol (TC), triglyceride (TG), LDL, and Lp-PLA2 levels in the HFFD group. HFFD also reduced HDL, IL-10, and TGF produced by CD4 and Tregs compared with the normal group. ACE at all doses significantly reduced Lp-PLA2 levels compared with the HFFD group (p < 0.05). Interestingly, the administration of 520 mg/kg BW ACE (D2) increased the production of IL-10 significantly compared to other doses (p < 0.05). The D3 group possessed a high TGF- production and Treg expression level significantly different between groups (p < 0.05). Foam cells were mostly found in the aorta of the HFFD group compared to the normal and ACE treatment groups. This study suggested that ACE could reduce Lp-PLA2 enzyme activity and foam cell formation through the immunosuppressive activity of IL-10 and TGF cytokines.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"28 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385842","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 : 2024-01-04DOI: 10.3897/pharmacia.71.e113854
Ryan Ramon, S. M. Warli, Nur Rasyid, W. Atmoko
Aim: This study compared semen quality, FSH, LH, and Testosterone levels in infertile males among smokers and non-smokers and semen quality among alcoholics and non alcoholics. Methods: A literature search was conducted across five databases in December 2021. The search for this article uses specific keywords tailored to each search database’s specifications. Results: A total of 15 studies with 12,503 infertile male participants included in this study. 8,025 were non-smokers, 4,477 were smokers, 210 were alcoholics and 407 were non alcoholics. The effect of tobacco smoking on sperm were more significant in smokers than in non-smokers. Alcohol consumption affects the quality and quantity of semen. Both tobacco smoking and alcohol consumption combined may amplify their negative effects toward semen parameters. Conclusion: Smoking and alcohol has a detrimental impact on conventional semen characteristics. Due to the harmful effects of both factors, men seeking reproduction should be advised to avoid these habits.
{"title":"Effect of tobacco smoking and alcohol consumption on semen quality and hormone reproductive levels in infertile males: A systematic review and meta analysis","authors":"Ryan Ramon, S. M. Warli, Nur Rasyid, W. Atmoko","doi":"10.3897/pharmacia.71.e113854","DOIUrl":"https://doi.org/10.3897/pharmacia.71.e113854","url":null,"abstract":"Aim: This study compared semen quality, FSH, LH, and Testosterone levels in infertile males among smokers and non-smokers and semen quality among alcoholics and non alcoholics.\u0000 Methods: A literature search was conducted across five databases in December 2021. The search for this article uses specific keywords tailored to each search database’s specifications.\u0000 Results: A total of 15 studies with 12,503 infertile male participants included in this study. 8,025 were non-smokers, 4,477 were smokers, 210 were alcoholics and 407 were non alcoholics. The effect of tobacco smoking on sperm were more significant in smokers than in non-smokers. Alcohol consumption affects the quality and quantity of semen. Both tobacco smoking and alcohol consumption combined may amplify their negative effects toward semen parameters.\u0000 Conclusion: Smoking and alcohol has a detrimental impact on conventional semen characteristics. Due to the harmful effects of both factors, men seeking reproduction should be advised to avoid these habits.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"29 12","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386966","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 : 2024-01-03DOI: 10.3897/pharmacia.71.e114967
Thi-Kim-Quy Ha, N. Pham-Khanh, Thanh-Khiet Nguyen
Finding new neuraminidase (N) inhibitors to improve anti-influenza treatment is necessary because of the high mutation rates of N protein. Over 3,000 flavones/flavonols and their synthesized products from the COCONUT database were performed in silico docking screening with N1-H274Y-oseltamivir protein (PDB ID: 3CL0). Several derivatives containing nitrogen heterocyclic groups or aromatic rings showed higher anti-neuraminidase potential than that of laninamivir. Especially, the linker groups between the flavone aglycone and nitrogen heterocyclic group created the interactions with the triad of arginine residues Arg118-Arg292-Arg371, which suggested these compounds could become bifunctional inhibitors against the influenza virus strains at the sialic acid binding site and the adjacent 430-cavity position through triad of arginine residues binding. ADMET indicators and the synthesis design strategy of the most suitable compound, ethyl 4-{2-[(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy]acetyl}piperazine-1-carboxylate, were also successfully predicted and it could be a concerned candidate for further wet-lab synthesis, in vivo and clinical study.
{"title":"Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors","authors":"Thi-Kim-Quy Ha, N. Pham-Khanh, Thanh-Khiet Nguyen","doi":"10.3897/pharmacia.71.e114967","DOIUrl":"https://doi.org/10.3897/pharmacia.71.e114967","url":null,"abstract":"Finding new neuraminidase (N) inhibitors to improve anti-influenza treatment is necessary because of the high mutation rates of N protein. Over 3,000 flavones/flavonols and their synthesized products from the COCONUT database were performed in silico docking screening with N1-H274Y-oseltamivir protein (PDB ID: 3CL0). Several derivatives containing nitrogen heterocyclic groups or aromatic rings showed higher anti-neuraminidase potential than that of laninamivir. Especially, the linker groups between the flavone aglycone and nitrogen heterocyclic group created the interactions with the triad of arginine residues Arg118-Arg292-Arg371, which suggested these compounds could become bifunctional inhibitors against the influenza virus strains at the sialic acid binding site and the adjacent 430-cavity position through triad of arginine residues binding. ADMET indicators and the synthesis design strategy of the most suitable compound, ethyl 4-{2-[(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy]acetyl}piperazine-1-carboxylate, were also successfully predicted and it could be a concerned candidate for further wet-lab synthesis, in vivo and clinical study.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"1 2","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139389060","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 : 2023-12-18DOI: 10.3897/pharmacia.70.e115501
Ida Musfiroh, G. Megawati, Dewi Marhaeni Diah Herawati, Okta Nama Putra, Evi Sylvia Nurrasjid
Obesity is a cause of comorbid diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension which is based on low-level chronic inflammation. The GPR-120 receptor plays a role in insulin sensitization which is related to diabetes mellitus which is a comorbid obesity. Omega-3 fatty acids are believed to possess anti-inflammatory properties, hence potentially serving as a preventive measure against obesity-related comorbidities. The aim of this study is to do a stability analysis of the binding affinity between nine specific chemicals derived from omega-3 and the active site of the human GPR120 receptor using molecular dynamics simulations. Docking analysis was performed using Discovery Studio Visualizer, AutoDock Tools 1.5.6, and molecular dynamic simulation with AMBER 16. In this study, we used neurotensin 8–13 as a natural ligand to bind with the neurotensin receptor. Based on the neurotensin receptor docking results, the ΔG values for the following compounds are close to the values for neurotensin 8–13 -6.41 kcal/mol; docosahexaenoic acid -8.96 kcal/mol; eicosapentaenoic acid -7.41 kcal/mol; and heneicosapentaenoic acid -6.34 kcal/mol. Neurotensin 8–13 forms hydrogen bonds with TYR146, ARG213, and PHE344 of the neurotensin receptor, whereas docosahexaenoic acid forms hydrogen bonds with TYR146. Meanwhile, the average RMSD fluctuations for each system, namely docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid, were 0.672, 0.437, and 0.650, respectively. The SASA of the neurotensin receptor-ligand complex showed similar fluctuations, with the average values for docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid being 230.40, 229.89, and 230.20 nm2.
{"title":"Molecular dynamic of omega-3 compounds as an anti-obesity agent into GPR-120 receptor","authors":"Ida Musfiroh, G. Megawati, Dewi Marhaeni Diah Herawati, Okta Nama Putra, Evi Sylvia Nurrasjid","doi":"10.3897/pharmacia.70.e115501","DOIUrl":"https://doi.org/10.3897/pharmacia.70.e115501","url":null,"abstract":"Obesity is a cause of comorbid diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension which is based on low-level chronic inflammation. The GPR-120 receptor plays a role in insulin sensitization which is related to diabetes mellitus which is a comorbid obesity. Omega-3 fatty acids are believed to possess anti-inflammatory properties, hence potentially serving as a preventive measure against obesity-related comorbidities. The aim of this study is to do a stability analysis of the binding affinity between nine specific chemicals derived from omega-3 and the active site of the human GPR120 receptor using molecular dynamics simulations. Docking analysis was performed using Discovery Studio Visualizer, AutoDock Tools 1.5.6, and molecular dynamic simulation with AMBER 16. In this study, we used neurotensin 8–13 as a natural ligand to bind with the neurotensin receptor. Based on the neurotensin receptor docking results, the ΔG values for the following compounds are close to the values for neurotensin 8–13 -6.41 kcal/mol; docosahexaenoic acid -8.96 kcal/mol; eicosapentaenoic acid -7.41 kcal/mol; and heneicosapentaenoic acid -6.34 kcal/mol. Neurotensin 8–13 forms hydrogen bonds with TYR146, ARG213, and PHE344 of the neurotensin receptor, whereas docosahexaenoic acid forms hydrogen bonds with TYR146. Meanwhile, the average RMSD fluctuations for each system, namely docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid, were 0.672, 0.437, and 0.650, respectively. The SASA of the neurotensin receptor-ligand complex showed similar fluctuations, with the average values for docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid being 230.40, 229.89, and 230.20 nm2.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"35 S144","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138965195","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 : 2023-12-18DOI: 10.3897/pharmacia.70.e114935
Bathula Sivakumar, Ilango Kaliappan
Cancer is the second leading cause of death worldwide, and breast cancer accounts for 6.27 million cases in the year 2022. In the present study, Quantitative Structural Activity Relationship (QSAR) studies were performed on a dataset of 39 molecules of Imidazolinone analogues using in random selection using QSARINS Software. The statistically validated (R2 = 0.8429 Q2loo = 0.7558) MLR model was used to predict the bioactivity of novel leads. Moreover, high-scoring compounds were exposed to molecular docking and molecular dynamic modeling study. Intended derivatives 1–23 exhibited the anticipated bioactivity using a QSAR model. Aforementioned molecules were tested for binding affinities with the target protein and the majority of them demonstrated excellent interactions with binding pocket residues. Molecular dynamics simulations using Desmond for 100 ns of top complexes 1, 7, 9, 13 and 19 showed critical structural data concerning Aurora kinase inhibition. There were stable hydrophobic and hydrophilic interfaces in the dynamic site of compounds with a leading chemical structure. The chemical interacts to the (PDB: 1MQ4) structure in a stable way, according to RMSD, RMSF, RoG, H-bond, and SASA analysis. Furthermore, the docking results have been confirmed by MM-PBSA and MM-GBSA. Based on our findings, we reported the inclusion of the necessary structural features of imidazolinone derivatives leads to the development of the potent candidates for further development.
{"title":"Lead drug discovery from imidazolinone derivatives with Aurora kinase inhibitors","authors":"Bathula Sivakumar, Ilango Kaliappan","doi":"10.3897/pharmacia.70.e114935","DOIUrl":"https://doi.org/10.3897/pharmacia.70.e114935","url":null,"abstract":"Cancer is the second leading cause of death worldwide, and breast cancer accounts for 6.27 million cases in the year 2022. In the present study, Quantitative Structural Activity Relationship (QSAR) studies were performed on a dataset of 39 molecules of Imidazolinone analogues using in random selection using QSARINS Software. The statistically validated (R2 = 0.8429 Q2loo = 0.7558) MLR model was used to predict the bioactivity of novel leads. Moreover, high-scoring compounds were exposed to molecular docking and molecular dynamic modeling study. Intended derivatives 1–23 exhibited the anticipated bioactivity using a QSAR model. Aforementioned molecules were tested for binding affinities with the target protein and the majority of them demonstrated excellent interactions with binding pocket residues. Molecular dynamics simulations using Desmond for 100 ns of top complexes 1, 7, 9, 13 and 19 showed critical structural data concerning Aurora kinase inhibition. There were stable hydrophobic and hydrophilic interfaces in the dynamic site of compounds with a leading chemical structure. The chemical interacts to the (PDB: 1MQ4) structure in a stable way, according to RMSD, RMSF, RoG, H-bond, and SASA analysis. Furthermore, the docking results have been confirmed by MM-PBSA and MM-GBSA. Based on our findings, we reported the inclusion of the necessary structural features of imidazolinone derivatives leads to the development of the potent candidates for further development.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":"337 ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139173347","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 : 2023-12-18DOI: 10.3897/pharmacia.70.e113577
Y. Voynikov, R. Gevrenova, D. Zheleva-Dimitrova, V. Balabanova, Irina Nikolova, Lyubomir Marinov, Iossif Benbassat, G. Momekov
Purslane (Portulaca oleracea L., Portulacaceae) is a widespread edible plant with significant ethnobotanical and ethnopharmacological importance. The plant is characteristic for the presence of a class of indoline amide glucoside alkaloids, called cyclo-dopa amides, or oleraceins. Additionally, a new, structurally similar to oleraceins, class of indole amides have been discovered recently, called oleraindoles. These compounds have been evaluated to possess antiinflammatory and anticholinesterase activities. Herein, utilizing UHPLC-Orbitrap-MS with MS2 filtering by diagnostic ion filtering (DIF), and diagnostic difference filtering (DDF) using different data analysis tools, eight compounds with oleraindole structure were tentatively identified.
{"title":"UHPLC-Orbitrap screening of oleraindoles in hydromethanolic extracts of Portulaca oleracea","authors":"Y. Voynikov, R. Gevrenova, D. Zheleva-Dimitrova, V. Balabanova, Irina Nikolova, Lyubomir Marinov, Iossif Benbassat, G. Momekov","doi":"10.3897/pharmacia.70.e113577","DOIUrl":"https://doi.org/10.3897/pharmacia.70.e113577","url":null,"abstract":"Purslane (Portulaca oleracea L., Portulacaceae) is a widespread edible plant with significant ethnobotanical and ethnopharmacological importance. The plant is characteristic for the presence of a class of indoline amide glucoside alkaloids, called cyclo-dopa amides, or oleraceins. Additionally, a new, structurally similar to oleraceins, class of indole amides have been discovered recently, called oleraindoles. These compounds have been evaluated to possess antiinflammatory and anticholinesterase activities. Herein, utilizing UHPLC-Orbitrap-MS with MS2 filtering by diagnostic ion filtering (DIF), and diagnostic difference filtering (DDF) using different data analysis tools, eight compounds with oleraindole structure were tentatively identified.","PeriodicalId":20086,"journal":{"name":"Pharmacia","volume":" 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138963551","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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