Home Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor
Article
Licensed
Unlicensed Requires Authentication

Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor

  • Mohammad Rizki Fadhil Pratama ORCID logo , Hadi Poerwono ORCID logo and Siswandono Siswodihardjo ORCID logo EMAIL logo
Published/Copyright: December 19, 2019
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 30 Issue 6

Abstract

Background

Previous studies have shown that 5-O-benzoylpinostrobin derivatives is a potential anti-breast cancer, with the highest potential being the HER2 inhibitors, is a protein’s member of the epidermal growth factor receptor (EGFR) family. Overexpression of EGFR itself is known to be one of the causes of other cancer, including non-small cell lung cancer (NSCLC). Thus, it is possible that 5-O-benzoylpinostrobin derivatives can also inhibit the overexpression of EGFR in NSCLC. In the case of NSCLC, mutations of EGFR are often found in several amino acids, such as L858R, T790M, and V948R. This study aimed to determine the potential of 5-O-benzoylpinostrobin derivatives as an inhibitor of wild type and L858R/T790M/V948R-mutant EGFR.

Methods

Docking was performed using AutoDock Vina 1.1.2 on both wild type and L858R/T790M/V948R-mutant EGFR. Parameters observed, consisted of free energy of binding (ΔG) and amino acid interactions of each ligand.

Results

Docking results showed that all 5-O-benzoylpinostrobin derivatives showed a lower ΔG for both wild type and L858R/T790M/V948R-mutant EGFR, with the lowest ΔG shown by 4-methyl-5-O-benzoylpinostrobin and 4-trifluoromethyl-5-O-benzoylpinostrobin. Both the ligands have the similarity of interacting amino acids compared to reference ligands between 76.47 and 88.24%. Specifically, the ΔG of all test ligands was lower in mutant EGFR than in the wild type, which indicates the potential of the ligand as EGFR inhibitors where a mutation to EGFR occurs.

Conclusions

These results confirm that 5-O-benzoylpinostrobin derivatives have the potential to inhibit EGFR in both wild type and L858R/T790M/V948R-mutant.

Keywords: 5-O-benzoylpinostrobin; EGFR; molecular docking; NSCLC; pinostrobin

Acknowledgments

This paper has been presented at the 8th APPEN Conference and 2nd HPC Conference on 8–9th October 2019, Universitas Airlangga, Surabaya, Indonesia.

  1. Research funding: None declared.

  2. Author contributions: All authors have contributed equally to the preparation of this manuscript. MRFP plays a role in the validation and docking process. HP and S play an equal role in the design of test compounds as well as research designs.

  3. Competing interests: All authors declare that there is no conflict of interest regarding the publication of this article.

References

[1] De Groot PM, Wu CC, Carter BW, Munden RF. The epidemiology of lung cancer. Transl Lung Cancer Res 2018;7:220–33.10.21037/tlcr.2018.05.06Search in Google Scholar PubMed PubMed Central

[2] Levine B, Kroemer G. Biological Functions of autophagy genes: a disease perspective. Cell 2019;176:11–42.10.1016/j.cell.2018.09.048Search in Google Scholar PubMed PubMed Central

[3] Bethune G, Bethune D, Ridgway N, Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis 2010;2:48–51.Search in Google Scholar

[4] Silva AP, Coelho PV, Anazetti M, Simioni PU. Targeted therapies for the treatment of non-small-cell lung cancer: monoclonal antibodies and biological inhibitors. Hum Vaccin Immunother 2017;13:843–53.10.1080/21645515.2016.1249551Search in Google Scholar PubMed PubMed Central

[5] Ni J, Zhang L. Evaluation of three small molecular drugs for targeted therapy to treat nonsmall cell lung cancer. Chin Med J 2016;129:332–40.10.4103/0366-6999.174484Search in Google Scholar PubMed PubMed Central

[6] Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol 2018;12:3–20.10.1002/1878-0261.12155Search in Google Scholar PubMed PubMed Central

[7] Kannan S, Venkatachalam G, Lim HH, Surana U, Verma C. Conformational landscape of the epidermal growth factor receptor kinase reveals a mutant specific allosteric pocket. Chem Sci 2018;9:5212–22.10.1039/C8SC01262HSearch in Google Scholar PubMed PubMed Central

[8] Tang J, Salama R, Gadgeel SM, Sarkar FH, Ahmad A. Erlotinib resistance in lung cancer: current progress and future perspectives. Front Pharmacol 2013;4:15.10.3389/fphar.2013.00015Search in Google Scholar PubMed PubMed Central

[9] Le T, Gerber DE. Newer-generation egfr inhibitors in lung cancer: how are they best used? Cancer 2019;11:E366.10.3390/cancers11030366Search in Google Scholar PubMed PubMed Central

[10] Sangpheak K, Tabtimmai L, Seetaha S, Rungnim C, Chavasiri W, Wolschann P, et al. Biological evaluation and molecular dynamics simulation of chalcone derivatives as epidermal growth factor-tyrosine kinase inhibitors. Molecules 2019;24:1092.10.3390/molecules24061092Search in Google Scholar PubMed PubMed Central

[11] Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv 2015;33:1582–614.10.1016/j.biotechadv.2015.08.001Search in Google Scholar PubMed PubMed Central

[12] Jaudan A, Sharma S, Malek SN, Dixit A. Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action. PLoS One 2018;13:e0191523.10.1371/journal.pone.0191523Search in Google Scholar PubMed PubMed Central

[13] Tan BC, Tan SK, Wong SM, Ata N, Rahman NA, Khalid N. Distribution of flavonoids and cyclohexenyl chalcone derivatives in conventional propagated and in vitro-derived field-grown Boesenbergia rotunda (L.) Mansf. Evid Based Complement Alternat Med 2015;2015:451870.10.1155/2015/451870Search in Google Scholar

[14] Junior WA, Gomes DB, Zanchet B, Schonell AP, Diel KA, Banzato TP, et al. Antiproliferative effects of pinostrobin and 5,6-dehydrokavain isolated from leaves of Alpinia zerumbet. Rev Bras Farmacogn 2017;27:592–8.10.1016/j.bjp.2017.05.007Search in Google Scholar

[15] Poerwono H, Sasaki S, Hattori Y, Higashiyama K. Efficient microwave-assisted prenylation of pinostrobin and biological evaluation of its derivatives as antitumor agents. Bioorg Med Chem Lett 2010;20:2086–9.10.1016/j.bmcl.2010.02.068Search in Google Scholar PubMed

[16] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 2010;31:455–61.10.1002/jcc.21334Search in Google Scholar PubMed PubMed Central

[17] O’Boyle NM, Banck M, James CA, Vandermeersch T, Hutchison GR. Open Babel: an open chemical toolbox. J Cheminformatics 2011;3:33.10.1186/1758-2946-3-33Search in Google Scholar PubMed PubMed Central

[18] Yuan S, Chan S, Hu Z. Using PyMOL as a platform for computational drug design. Wiley Interdiscip Rev Comput Mol Sci 2017;7:e1298.10.1002/wcms.1298Search in Google Scholar

[19] Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605–12.10.1002/jcc.20084Search in Google Scholar PubMed

[20] Pratama MR, Sutomo S. Chemical structure optimization of lupeol as ER-A and HER2 inhibitor. Asian J Pharm Clin Res 2018;11:298–303.10.22159/ajpcr.2018.v11i6.24226Search in Google Scholar

[21] Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: a review. Biophys Rev 2017;9:91–102.10.1007/s12551-016-0247-1Search in Google Scholar PubMed PubMed Central

[22] Forli S. Charting a path to success in virtual screening. Molecules 2015;20:18732–58.10.3390/molecules201018732Search in Google Scholar PubMed PubMed Central

[23] Feinstein WP, Brylinski M. Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets. J Cheminform 2015;7:18.10.1186/s13321-015-0067-5Search in Google Scholar PubMed PubMed Central

[24] Lelais G, Epple R, Marsije TH, Long YO, McNeill M, Chen B, et al. Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a novel, potent, and WT sparing covalent inhibitor of oncogenic (L858R, ex19del) and Resistant (T790M) EGFR mutants for the treatment of EGFR mutant non-small-cell lung cancers. J Med Chem 2016;59:6671–89.10.1021/acs.jmedchem.5b01985Search in Google Scholar PubMed

[25] Cheng H, Nair SK, Murray BW, Almaden C, Bailey S, Baxi S, et al. Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a potent, WT Sparing, irreversible inhibitor of T790M-containing EGFR mutants. J Med Chem 2016;59:2005–24.10.1021/acs.jmedchem.5b01633Search in Google Scholar PubMed

[26] Srivastava JK, Pillai GG, Bhat HR, Verma A, Singh UP. Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating epidermal growth factor receptor tyrosine kinase. Sci Rep 2017;7:5851.10.1038/s41598-017-05934-5Search in Google Scholar PubMed PubMed Central

[27] Megantara S, Iwo MI, Levita J, Ibrahim S. Determination of ligand position in aspartic proteases by correlating Tanimoto coefficient and binding affinity with root mean square deviation. J App Pharm Sci 2016;6:125–9.10.7324/JAPS.2016.600120Search in Google Scholar

[28] Castro-Alvarez A, Costa AM, Vilarrasa J. The performance of several docking programs at reproducing protein-macrolide-like crystal structures. Molecules 2017;22:E136.10.3390/molecules22010136Search in Google Scholar PubMed PubMed Central

[29] Atkovska K, Samsonov SA, Paszkowski-Rogacz M, Pisabarro MT. Multipose binding in molecular docking. Int J Mol Sci 2014;15:2622–45.10.3390/ijms15022622Search in Google Scholar PubMed PubMed Central

[30] Forli S, Huey R, Pique ME, Sanner M, Goodsell DS, Olson AJ. Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc 2016;11:905–19.10.1038/nprot.2016.051Search in Google Scholar PubMed PubMed Central

[31] Natesan S, Subramaniam R, Bergeron C, Balaz S. Binding affinity prediction for ligands and receptors forming tautomers and ionization species: inhibition of mitogen-activated protein kinase-activated protein kinase 2 (MK2). J Med Chem 2012;55:2035–47.10.1021/jm201217qSearch in Google Scholar PubMed PubMed Central

[32] Pratama MR, Suratno S, Mulyani E. Antibacterial activity of akar kuning (Arcangelisia flava) secondary metabolites: molecular docking approach. Asian J Pharm Clin Res 2018;11:447–51.10.22159/ajpcr.2018.v11i11.29189Search in Google Scholar

[33] Singh H, Srivastava HK, Raghava GP. A web server for analysis, comparison and prediction of protein ligand binding sites. Biol Direct 2016;11:14.10.1186/s13062-016-0118-5Search in Google Scholar PubMed PubMed Central

[34] Miller RL, Thompson AA, Trapella C, Guerrini R, Malfacini D, Patel N, et al. The importance of ligand-receptor conformational pairs in stabilization: spotlight on the N/OFQ G protein-coupled receptor. Structure 2015;23:2291–9.10.1016/j.str.2015.07.024Search in Google Scholar PubMed PubMed Central

[35] Ferreira LG, dos Santos RN, Oliva G, Andricopulo AD. Molecular docking and structure-based drug design strategies. Molecules Molecules Molecules Molecules 2015;20:13384–421.10.3390/molecules200713384Search in Google Scholar PubMed PubMed Central

[36] Ramirez D, Caballero J. Is it reliable to take the molecular docking top scoring position as the best solution without considering available structural data? Molecules 2018;23:1038.10.3390/molecules23051038Search in Google Scholar PubMed PubMed Central

[37] Le T, Gerber DE. Newer-Generation EGFR Inhibitors in lung cancer: how are they best used? Cancers 2019;11:366.10.3390/cancers11030366Search in Google Scholar PubMed PubMed Central

[38] Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008;105:2070–5.10.1073/pnas.0709662105Search in Google Scholar PubMed PubMed Central

[39] Minari R, Bordi P, Tiseo M. Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors in T790M-positive non-small cell lung cancer: review on emerged mechanisms of resistance. Transl Lung Cancer Res 2016;5:695–708.10.21037/tlcr.2016.12.02Search in Google Scholar PubMed PubMed Central

[40] Nishio M, Murakami H, Ohe Y, Hida T, Sakai H, Kasahara K, et al. Phase I study of TAS-121, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with non-small-cell lung cancer harboring EGFR mutations. Invest New Drugs 2019;(37):1207–17.10.1007/s10637-019-00732-4Search in Google Scholar PubMed PubMed Central

[41] Kubinyi H. QSAR: Hansch Analysis and Related Approaches. In: Mannhold R, Krogsgaard-Larsen P, Timmerman H, editors. QSAR: hansch analysis and related approaches. Weinheim: VCH Verlagsgesellschaft mbH, 1993:21–6.10.1002/9783527616824.ch3Search in Google Scholar

[42] Pratama MR, Gusdinar T. Docking study of secondary metabolites from Glycyrrhiza glabra as PPAR-γ agonist. Biointerface Res Appl Chem 2019;9:4006–10.10.33263/BRIAC94.006010Search in Google Scholar

[43] Mortier J, Dhakal P, Volkamer A. Truly Target-focused pharmacophore modeling: a novel tool for mapping intermolecular surfaces. Molecules 2018;23:1959.10.3390/molecules23081959Search in Google Scholar PubMed PubMed Central

[44] Martin-Fernandez ML, Clarke DT, Roberts SK, Zanetti-Domingues LC, Gervasio FL. Structure and dynamics of the EGF receptor as revealed by experiments and simulations and its relevance to non-small cell lung cancer. Cells 2019;8:316.10.3390/cells8040316Search in Google Scholar PubMed PubMed Central

[45] Schaefer C, Rost B. Predict impact of single amino acid change upon protein structure. BMC Genomics 2012;13:S4.10.1186/1471-2164-13-S4-S4Search in Google Scholar PubMed PubMed Central

Supplementary Material

The online version of this article offers supplementary material (DOI: https://doi.org/10.1515/jbcpp-2019-0301).

Received: 2019-10-13
Accepted: 2019-11-07
Published Online: 2019-12-19

© 2019 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Reviews
  2. Pharmacist contributions in the treatment of diabetes mellitus in Southeast Asia: a narrative review
  3. The implementation of a chronic disease management program (Prolanis) in Indonesia: a literature review
  4. Original Articles
  5. Quercetin attenuates acute predator stress exposure-evoked innate fear and behavioral perturbation
  6. Evaluating current practices and policies in the use of injectable medicines for treating myalgia in a primary care center in Pamekasan, Indonesia
  7. The contemporary role and potential of pharmacist contribution for community health using social media
  8. Evaluation of rational drug use based on World Health Organization prescribing indicators in a primary care center in Pamekasan East Java, Indonesia
  9. The prescription patterns of second-generation antipsychotics in schizophrenia outpatient setting
  10. Factors affecting community pharmacist’s service for women with chronic diseases during pregnancy and breastfeeding: application of the Health Belief Model
  11. Overview of therapeutic changes in antiepileptic drugs in adult patients
  12. Exploration of barriers affecting job satisfaction among community pharmacists
  13. Patients’ characteristics and their adherence to insulin therapy
  14. Correlation of chemotherapy costs with quality of life in nasopharyngeal cancer patients
  15. Impact of educational preeclampsia prevention booklet on knowledge and adherence to low dose aspirin among pregnant women with high risk for preeclampsia
  16. Translation, cultural adaptation, and validation of the quality of well being self-administered questionnaire in general population in Indonesia
  17. Knowledge, attitude, and practice of pharmacists towards management of hypertension in primary care centers
  18. Medication adherence in diabetes mellitus patients at Tanjung Karang Primary Health Care Center, Mataram
  19. Decreasing angiogenesis vasa vasorum through Lp-PLA2 and H2O2 inhibition by PSP from Ganoderma lucidum in atherosclerosis: in vivo diabetes mellitus type 2
  20. Antiaggregation effect of clopidogrel in coronary heart disease patients using omeprazole
  21. The effect of curcuma (Curcuma xanthorrizha roxb.) extract as an adjuvant of captopril therapy on cardiac histopathology of male mice (Mus musculus) with hypertension
  22. Coenzyme Q10 nanostructured lipid carriers as an inducer of the skin fibroblast cell and its irritability test in a mice model
  23. Medical problems in patients with chronic kidney disease undergoing hemodialysis and their therapy
  24. ADMET properties of novel 5-O-benzoylpinostrobin derivatives
  25. Development of nonalcoholic fatty liver disease model by high-fat diet in rats
  26. Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor
  27. The relationship between the level of education and accuracy of insulin injection techniques in DM patients with measurement of HbA1c values
  28. The effect of premixed insulin to blood glucose concentration in patients with type 2 diabetes mellitus
  29. Intravenous insulin therapy in diabetes mellitus with hyperglycemic crisis and intercurrent illness
  30. Adherence behavior assessment of oral antidiabetic medication use: a study of patient decisions in long-term disease management in primary health care centers in Surabaya
  31. Evaluation to the chemotherapy use in patients with diffuse large B-cell lymphoma
  32. Analysis of the use and cost of stress ulcer prophylaxis for surgical inpatients
  33. Antineuroinflammation activity of n-butanol fraction of Marsilea crenata Presl. in microglia HMC3 cell line
  34. The enhancement of Arg1 and activated ERβ expression in microglia HMC3 by induction of 96% ethanol extract of Marsilea crenata Presl. leaves
  35. Ternary solid dispersion to improve solubility and dissolution of meloxicam
  36. Improving solubility and dissolution of meloxicam by solid dispersion using hydroxypropyl methylcellulose 2910 3 cps and nicotinamide
  37. o-Hydroxycinnamic derivatives as prospective anti-platelet candidates: in silico pharmacokinetic screening and evaluation of their binding sites on COX-1 and P2Y12 receptors
  38. The change of proinflammatory cytokine tumor necrosis factor α level in the use of meloxicam in rat model of osteoarthritis
  39. Attenuation of IL-1ß on the use of glucosamine as an adjuvant in meloxicam treatment in rat models with osteoarthritis
  40. Analysis of effectiveness and drug related problems of pain reliever for knee osteoarthritis: weighing clinical risk and benefit
  41. Comparison of antibiotic prescriptions in adults and children with upper respiratory tract infections in Bangka Tengah primary health care centers
  42. Profile of sociodemographics, sources of infection, antiretrovirals and CD4 counts on HIV/AIDS outpatients in Turen Primary Health Centre, Indonesia
  43. Synergistic anti-hepatitis C virus activity of Ruta angustifolia extract with NS3 protein inhibitor
  44. In vitro equivalence of generic and branded amoxicillin tablet by microbiological assay method
  45. Knowledge and attitude: two fundamental factors that determine patient compliance in antibiotic therapy
  46. Molecular docking study of sappan wood extract to inhibit PBP2A enzyme on methicillin-resistant Staphylococcus aureus (MRSA)
  47. Effect of curcumin analogue synthetic product from cullilawan oil for the liver damage treatment in male mice (Mus musculus L.)
  48. Case Report
  49. A case report of generalized tetanus in a 42-year-old man with dental infection
https://doi.org/10.1515/jbcpp-2019-0301
Keywords for this article
5-O-benzoylpinostrobin; EGFR; molecular docking; NSCLC; pinostrobin

Articles in the same Issue

  1. Reviews
  2. Pharmacist contributions in the treatment of diabetes mellitus in Southeast Asia: a narrative review
  3. The implementation of a chronic disease management program (Prolanis) in Indonesia: a literature review
  4. Original Articles
  5. Quercetin attenuates acute predator stress exposure-evoked innate fear and behavioral perturbation
  6. Evaluating current practices and policies in the use of injectable medicines for treating myalgia in a primary care center in Pamekasan, Indonesia
  7. The contemporary role and potential of pharmacist contribution for community health using social media
  8. Evaluation of rational drug use based on World Health Organization prescribing indicators in a primary care center in Pamekasan East Java, Indonesia
  9. The prescription patterns of second-generation antipsychotics in schizophrenia outpatient setting
  10. Factors affecting community pharmacist’s service for women with chronic diseases during pregnancy and breastfeeding: application of the Health Belief Model
  11. Overview of therapeutic changes in antiepileptic drugs in adult patients
  12. Exploration of barriers affecting job satisfaction among community pharmacists
  13. Patients’ characteristics and their adherence to insulin therapy
  14. Correlation of chemotherapy costs with quality of life in nasopharyngeal cancer patients
  15. Impact of educational preeclampsia prevention booklet on knowledge and adherence to low dose aspirin among pregnant women with high risk for preeclampsia
  16. Translation, cultural adaptation, and validation of the quality of well being self-administered questionnaire in general population in Indonesia
  17. Knowledge, attitude, and practice of pharmacists towards management of hypertension in primary care centers
  18. Medication adherence in diabetes mellitus patients at Tanjung Karang Primary Health Care Center, Mataram
  19. Decreasing angiogenesis vasa vasorum through Lp-PLA2 and H2O2 inhibition by PSP from Ganoderma lucidum in atherosclerosis: in vivo diabetes mellitus type 2
  20. Antiaggregation effect of clopidogrel in coronary heart disease patients using omeprazole
  21. The effect of curcuma (Curcuma xanthorrizha roxb.) extract as an adjuvant of captopril therapy on cardiac histopathology of male mice (Mus musculus) with hypertension
  22. Coenzyme Q10 nanostructured lipid carriers as an inducer of the skin fibroblast cell and its irritability test in a mice model
  23. Medical problems in patients with chronic kidney disease undergoing hemodialysis and their therapy
  24. ADMET properties of novel 5-O-benzoylpinostrobin derivatives
  25. Development of nonalcoholic fatty liver disease model by high-fat diet in rats
  26. Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor
  27. The relationship between the level of education and accuracy of insulin injection techniques in DM patients with measurement of HbA1c values
  28. The effect of premixed insulin to blood glucose concentration in patients with type 2 diabetes mellitus
  29. Intravenous insulin therapy in diabetes mellitus with hyperglycemic crisis and intercurrent illness
  30. Adherence behavior assessment of oral antidiabetic medication use: a study of patient decisions in long-term disease management in primary health care centers in Surabaya
  31. Evaluation to the chemotherapy use in patients with diffuse large B-cell lymphoma
  32. Analysis of the use and cost of stress ulcer prophylaxis for surgical inpatients
  33. Antineuroinflammation activity of n-butanol fraction of Marsilea crenata Presl. in microglia HMC3 cell line
  34. The enhancement of Arg1 and activated ERβ expression in microglia HMC3 by induction of 96% ethanol extract of Marsilea crenata Presl. leaves
  35. Ternary solid dispersion to improve solubility and dissolution of meloxicam
  36. Improving solubility and dissolution of meloxicam by solid dispersion using hydroxypropyl methylcellulose 2910 3 cps and nicotinamide
  37. o-Hydroxycinnamic derivatives as prospective anti-platelet candidates: in silico pharmacokinetic screening and evaluation of their binding sites on COX-1 and P2Y12 receptors
  38. The change of proinflammatory cytokine tumor necrosis factor α level in the use of meloxicam in rat model of osteoarthritis
  39. Attenuation of IL-1ß on the use of glucosamine as an adjuvant in meloxicam treatment in rat models with osteoarthritis
  40. Analysis of effectiveness and drug related problems of pain reliever for knee osteoarthritis: weighing clinical risk and benefit
  41. Comparison of antibiotic prescriptions in adults and children with upper respiratory tract infections in Bangka Tengah primary health care centers
  42. Profile of sociodemographics, sources of infection, antiretrovirals and CD4 counts on HIV/AIDS outpatients in Turen Primary Health Centre, Indonesia
  43. Synergistic anti-hepatitis C virus activity of Ruta angustifolia extract with NS3 protein inhibitor
  44. In vitro equivalence of generic and branded amoxicillin tablet by microbiological assay method
  45. Knowledge and attitude: two fundamental factors that determine patient compliance in antibiotic therapy
  46. Molecular docking study of sappan wood extract to inhibit PBP2A enzyme on methicillin-resistant Staphylococcus aureus (MRSA)
  47. Effect of curcumin analogue synthetic product from cullilawan oil for the liver damage treatment in male mice (Mus musculus L.)
  48. Case Report
  49. A case report of generalized tetanus in a 42-year-old man with dental infection
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 10.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2019-0301/html
Scroll to top button