Startseite Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells
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Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells

  • Melanny Ika Sulistyowaty EMAIL logo , Retno Widyowati ORCID logo , Galih Satrio Putra , Tutuk Budiati und Katsuyoshi Matsunami
Veröffentlicht/Copyright: 25. Juni 2021
Journal of Basic and Clinical Physiology and Pharmacology
Aus der Zeitschrift Journal of Basic and Clinical Physiology and Pharmacology Band 32 Heft 4

Abstract

Objectives

This study aims to synthesize a series of benzoxazines (1–5) to be examined as an epidermal growth factor receptor (EGFR) inhibitor by in-silico study. The overexpression of EGFR causes the growth of normal lung cells to become uncontrollable, which may lead to cancer formation. We also conducted the absorption, distribution, metabolism, excretions and toxicity (ADMET) properties evaluation and also examined in vitro anticancer assay on human lung cancer cells line, which is A549.

Methods

Benzoxazines (1–5) were synthesized by reacting anthranilic acid and benzoyl chlorides. The structures of the compounds were determined with 1H, 13C-NMR, HRMS, UV and FT-IR spectrometric methods. Prediction of ADMET was using online pkCSM, and the molecular docking studies were using MVD with EGFR-TKIs as the target (PDB ID: 1M17). In vitro assay of anticancer activity was performed by MTT assay.

Results

Compounds 1–5 were successfully synthesized in good yields (71–84%). The ADMET prediction showed that benzoxazines are able to be absorbed through GIT, metabolized by CYP 450, and not hepatotoxic. The title compounds have a greater Moldock Score than Erlotinib, and 3 has the highest activity against A549 compared with other benzoxazines, IC50=36.6 μg/mL.

Conclusions

Compound (3) more active as anticancer against Human cancer cells line compared with other benzoxazines.

Keywords: A549 cancer cell; ADMET prediction; benzoxazines; molecular docking; synthesis
Corresponding author: Melanny Ika Sulistyowaty, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia, E-mail:

Acknowledgments

The authors are thankful to Prof. Katsuyoshi Matsunami from Hiroshima University for facility for conducting bioassay experiments and also grateful to Prof. Siswandono from Faculty of Pharmacy, Universitas Airlangga, Indonesia for Molegro® facility for this research.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

References

1. The Global Cancer Observatory. Indonesia fact sheet. Available from: https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf [Accessed 1 May 2019].Suche in Google Scholar

2. Gillian, B, Drew, B, Neale, R, Zhaolin, X. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis 2010;2:48–51.Suche in Google Scholar

3. Sousa, AC, Silveira, C, Janeiro, A, Malveiro, S, Oliveira, AR, Felizardo, M, et al.. Detection of rare and novel EGFR mutations in NSCLC patients: implications for treatment-decision. Lung Canc 2020;139:35–40.10.1016/j.lungcan.2019.10.030Suche in Google Scholar

4. Grigoriu, B, Berghmans, T, Meert, AP. Management of EGFR mutated nonsmall cell lung carcinoma patients. Eur Respir J 2015;45:1132–41.10.1183/09031936.00156614Suche in Google Scholar

5. Kesuma, D, Putra, GS, Yuniarta, TA, Sulistyowaty, MI, Siswandono, BT. Synthesis of 2-phenyl-4H-benzo[d][1,3]oxazin-4-one and its biological activity against A549 cancer cell line through methionyl-tRNA synthetase inhibition approach on in-silico studies. Int J Pharmaceut Res 2019;11:1–11.Suche in Google Scholar

6. El-Azab, Adel, S, Al-Omar, MA, Abdel-Aziz, AAM, Abdel-Aziz, NI, El-Sayed, MAA, et al.. Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: molecular docking study. Eur J Med Chem 2010;45:4188–98.10.1016/j.ejmech.2010.06.013Suche in Google Scholar

7. Bharathkumar, H, Mohan, CD, Rangappa, S, Kang, T, Keerthy, HK, Fuchs, JE, et al.. Screening of quinoline, 1,3-benzoxazine, and 1,3-Oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis. Org Biomol Chem 2015;36:1–21.10.1039/C5OB00791GSuche in Google Scholar

8. Jiao, P-F, Zhao, B-X, Wang, W-W, He, Q-X, Wan, M-S, Shin, D-S, et al.. Design, synthesis, and preliminary biological evaluation of 2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine derivatives. Bioorg Med Chem Lett 2006;16:2862–7.10.1016/j.bmcl.2006.03.013Suche in Google Scholar

9. Su, H, Su, L, He, Q, Zhao, J, Zhao, B, Zhang, S, et al.. A benzoxazine derivative specifically inhibits cell cycle progression in p53-wild type pulmonary adenocarcinoma cells. Front Biol 2010;5:180–6.10.1007/s11515-010-0031-8Suche in Google Scholar

10. Putra, GS, Widiyana, AP, Muchlashi, LA, Sulistyowaty, MI, Ekowati, J, Budiati, T. The influence of ratio pyridine and triethylamine catalysts on synthesis 2-phenyl-benzo[D] [1,3] oxazine-4-on derivatives. J Chem Pharmaceut Res 2017;9:73–80.10.20473/jfiki.v3i22016.44-48Suche in Google Scholar

11. Sulistyowaty, MI, Putra, GS, Budiati, T, Matsunami, K. Synthesis, in vitro anticancer activity and in silico study of some benzylidenehydrazide derivatives. Key Eng Mater 2020;840:277–83.10.4028/www.scientific.net/KEM.840.277Suche in Google Scholar

12. Thomas, HA. Merck molecular force field. I basis, form, scope, parametrization, and performance of MMFF94. J Comb Chem 1996;17:490–519.10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-PSuche in Google Scholar

13. Stamos, J, Sliwkowski, MX, Eigenbrot, C. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem 2002;48:46265–72.10.1074/jbc.M207135200Suche in Google Scholar

14. Thomsen, R, Christensen, MH. MolDock: a new technique for high-accuracy molecular docking. J Med Chem 2006;49:3315–21.10.1021/jm051197eSuche in Google Scholar

15. Jayaram, B, Tanya, S, Goutam, M, Abhinav, M, Shashank, S, Vandana, S. Sanjeevini: a freely accessible web-server for target directed lead molecule discovery. BMC Bioinf 2012;13:S7.10.1186/1471-2105-13-S17-S7Suche in Google Scholar PubMed PubMed Central

16. Pires, DEV, Blundell, TL, Ascher, DB. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem 2015;58:4066−72.10.1021/acs.jmedchem.5b00104Suche in Google Scholar PubMed PubMed Central

17. Drug Enforcement Administration (DEA). US Department of Justice. Part 1308 — schedules of controlled substances. Link to an amendment published at 85 FR 5322, Jan. 30, 2020.Suche in Google Scholar

18. Undang-Undang Republik Indonesia. Nomor 35 Tahun 2009. About Narkotika. In: Tahun. Jakarta: Penerbit Manuscript; 2009.Suche in Google Scholar

19. Trevor, AJ, Katzung, BG, Kruidering-Hall, M. Katzung and Trevor’s. pharmacology examination & board review, 11th ed. New York: The McGraw-Hill Education; 2015.Suche in Google Scholar

20. Shargel, L, Yu, ABC. Applied biopharmaceutics & pharmacokinetics, 7th ed. New York: The McGraw-Hill Companies; 2016.Suche in Google Scholar

21. BC Cancer Agency Cancer Drug Manual. Erlotinib. Available from: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Erlotinib_monograph_1July2014.pdf [Accessed 1 Mar 2019].Suche in Google Scholar

22. Singh, S, Khanna, VK, Pant, AB. Development of in vitro toxicology: a historic story. In: Dhawan, A, Kwon, S, editors. In vitro toxicology. London: Academic Press; 2018.10.1016/B978-0-12-804667-8.00001-8Suche in Google Scholar

23. Wishart, DS, Knox, C, Guo, AC, Shrivastava, S, Hassanali, M, Stothard, P, et al.. Drugbank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 2006;1:34.10.1093/nar/gkj067Suche in Google Scholar PubMed PubMed Central

24. Usdin, E, Efron, DH. Psychotropic drugs and related compounds, 2nd ed. Washington DC: National Institute of Mental Health; 1972.10.1037/e475422004-001Suche in Google Scholar

25. Batista, R, Júnior, AJS, Braga de Oliveira, A. Plant derived antimalarial agents: new leads and efficient phytomedicines. Part II. Non-alkaloidal natural products. Molecules 2009;14:3037–72.10.3390/molecules14083037Suche in Google Scholar PubMed PubMed Central

26. Cos, P, Vlietinck, AJ, Berghe, DV, Maesa, L. Anti-infective potential of natural products: how to develop a stronger in vitro ‘proof-of-concept’. J Ethnopharmacol 2006;106:290–302.10.1016/j.jep.2006.04.003Suche in Google Scholar PubMed

27. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology non-small cell lung cancer ver.2; 2018. Available from: https://www2.tri-kobe.org/nccn/guideline/lung/english/non_small.pdf [Accessed 1 Jan 2019].Suche in Google Scholar
Received: 2020-11-28
Accepted: 2021-03-03
Published Online: 2021-06-25

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Original Articles
  3. Cost of illness of diabetes mellitus in Indonesia: a systematic review
  4. Social media health interventions to improve diabetes mellitus patient outcome: a systematic review
  5. Developing pharmacokinetics–pharmacodynamics model of valproic acid syrup based on prediction of population pharmacokinetics parameter and seizure frequency in Indonesian pediatric epilepsy outpatients
  6. Acetylcholinesterase inhibitory activity of extract and fractions from the root of Rauvolfia serpentina(L.) Bth.ex Kurz
  7. Green tea and its active compound epigallocathechin-3-gallate (EGCG) inhibit neuronal apoptosis in a middle cerebral artery occlusion (MCAO) model
  8. The effects of quercetin on nicotine-induced reward effects in mice
  9. Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior
  10. Translation and cross-cultural adaption of an instrument measuring patient’s well-being under treatment for schizophrenia
  11. Quercetin promotes behavioral recovery and biomolecular changes of melanocortin-4 receptor in mice with ischemic stroke
  12. Knowledge and attitudes of healthcare professionals on prescribing errors
  13. Inhibition of Ras and STAT3 activity of 4-(tert-butyl)-N-carbamoylbenzamide as antiproliferative agent in HER2-expressing breast cancer cells
  14. Predicting the molecular mechanism of glucosamine in accelerating bone defect repair by stimulating osteogenic proteins
  15. Larvicidal toxicity and parasporal inclusion of native Bacillus thuringiensis BK5.2 against Aedes aegypti
  16. Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells
  17. Thymoquinone and its derivatives against breast cancer with HER2 positive: in silico studies of ADMET, docking and QSPR
  18. Assessment of patient understanding of their conventional cardiac medicines and herbal prepared/derived products: preliminary survey and interviews with selected community-dwelling elderly patients in the Philippines
  19. The development and validation of the health belief model questionnaire for measuring factors affecting adherence in the elderly with hypertension
  20. Analysis of the side effect of QTc interval prolongation in the bedaquiline regimen in drug resistant tuberculosis patients
  21. Shallot skin profilling, computational evaluation of physicochemical properties, ADMET, and molecular docking of its components against P2Y12 receptor
  22. Analysis of HMGB-1 level before and after providing atorvastatin standard therapy in coronary artery disease patients with type-2 diabetes mellitus compared to without type-2 diabetes mellitus
  23. Analysis of matrix metalloproteinase-9 levels among acute heart failure patients with ACE inhibitor therapy (Dr. Soetomo Regional General Hospital, Surabaya)
  24. The correlation between self-related adherence, asthma-related quality of life and control of asthma in adult patients
  25. Providing counseling through home pharmacy care (HPC) for hemodialysis patients with hypertension in lowering blood pressure
  26. Community knowledge and attitude in recognizing asthma symptoms and using medication for asthma attacks: a cross-sectional study
  27. A study of anticoagulant therapy in patients with coronary artery disease
  28. The association of FKBP5 polymorphism with asthma susceptibility in asthmatic patients
  29. Gastroprotective effect of fluvoxamine and ondansetron on stress-induced gastric ulcers in mice
  30. Osteoblast iron genes: real time PCR and microarray hybridization approach under hyperoxia
  31. Attenuation of hyperplasia in lung parenchymal and colonic epithelial cells in DMBA-induced cancer by administering Andrographis paniculata Nees extract using animal model
  32. N-nitrosodiethylamine induces inflammation of liver in mice
  33. AST/ALT levels, MDA, and liver histopathology of Echinometra mathaei ethanol extract on paracetamol-induced hepatotoxicity in rats
  34. Development, characterization, molecular docking, and in vivo skin penetration of coenzyme Q10 nanostructured lipid carriers using tristearin and stearyl alcohol for dermal delivery
  35. The effect of Camellia sinensis (green tea) with its active compound EGCG on neuronal cell necroptosis in Rattus norvegicus middle cerebral artery occlusion (MCAO) model
  36. Hepatoprotective effect of ethanolic extract of sugarcane (Saccharum officinarum Linn.) leaves
  37. Correlation between the exposure time to mobile devices and the prevalence of evaporative dry eyes as one of the symptoms of computer vision syndrome among Senior High School students in East Java, Indonesia
  38. The effect of various high-fat diet on liver histology in the development of NAFLD models in mice
  39. Fabrication and characterization of bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked by glutaraldehyde for bone regeneration
  40. Health related quality of life among postmenopausal woman with hormone responsive HER2− breast cancer in Indonesia
  41. Gender differences in the blood glucose type 2 diabetes patients with combination rapid and long acting insulin therapy
  42. Correlation of dietary iron intake and serum iron with thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels in adult hyperthyroid patients
  43. The effect of pillbox use and education by pharmacist toward medication adherence in diabetes mellitus patients in a Primary Health Care Center in Mataram
  44. Variation concentration effect of propyleneglycol, glycerin, and polyethyleneglycol 400 to physical properties and dissolution rate of loratadine liquisolid tablet
  45. Role of Centella asiatica and ceramide in skin barrier improvement: a double blind clinical trial of Indonesian batik workers
  46. Secondary metabolite and antipyretic effects of Maja (Crescentia cujete L.) in fever-induced mice
  47. Hydration effect on kidney function and serum electrolyte in children with tumor lysis syndrome (TLS) and risk of TLS
  48. Drug utilization study and cost analysis of adult β-thalassemia major patient therapy at Dr. Soetomo General Hospital Surabaya
  49. The role of hyperbaric oxygen to platelet aggregation in noninsulin-dependent diabetes mellitus (NIDDM)
  50. Cocrystal formation of loratadine-succinic acid and its improved solubility
  51. The role of chondroitin sulfate to bone healing indicators and compressive strength
  52. The effects of quercetin on the expression of SREBP-1c mRNA in high-fat diet-induced NAFLD in mice
  53. Analysis of stress ulcer prophylaxis drug regimentation in surgical patients
  54. The stability and irritability study of the chitosan–Aloe vera spray gel as wound healing
  55. Effectiveness of citicoline in pediatric patients with refractive amblyopia in Surabaya, East Java, Indonesia
  56. The thermodynamic study of p-methoxycinnamic acid inclusion complex formation, using β-cyclodextrin and hydroxypropyl-β-cyclodextrin
  57. The effect of chitosan type and drug-chitosan ratio on physical characteristics and release profile of ketoprofen microparticles prepared by spray drying
  58. The maximum dose and duration in the therapy single use methotrexate to achieve remission by rheumatoid arthritis patients through disease activity score 28 (DAS28)
  59. Knowledge, attitudes, and practices (KAP) towards COVID-19 among university students in Pakistan: a cross-sectional study
  60. The impact of glutaraldehyde on the characteristics of bovine hydroxyapatite-gelatin based bone scaffold as gentamicin delivery system
  61. Analysis of the use of antibiotics profile and factors of surgical site infections study on digestive and oncology surgeries
  62. Second internal transcribed spacer (ITS-2) as genetic marker for molecular characterization of Sarcoptes scabiei in rabbits from several areas of East Java, Indonesia
  63. Design of gossypetin derivatives based on naturally occurring flavonoid in Hibiscus sabdariffa and the molecular docking as antibacterial agents
  64. Discovery of new targeting agents against GAPDH receptor for antituberculosis drug delivery
  65. The effect of red passion fruit (Passiflora edulis Sims.) fermentation time on its activity against Extended Strain Methicillin-Resistant (ESBL) Escherichia coli and Methicillin-Resistant Staphylococcus aureus (MRSA)
  66. Antibiotic use on acute respiratory tract infection nonpneumonia and nonspecific diarrhea in Primary Health Care Centre in Banjarbaru City, South Kalimantan, Indonesia
  67. Screening of anti-HIV activities in ethanol extract and fractions from Ficus fistulosa leaves
  68. The characteristics of lactic acid bacteria isolated from fermented food as potential probiotics
  69. Profile of gyrA gene mutation in clinical isolate of levofloxacin resistant Escherichia coli
  70. Antimicrobial activity of Centella asiatica and Gigantochloa apus
  71. Drug-related problems of antibiotic use in gastroenteritis related to patient therapy outcomes at Universitas Gadjah Mada Hospital
  72. The impact of suitability of empirical antibiotics use on therapeutic outcome of respiratory tract infection patients at inpatient wards of Universitas Gadjah Mada Academic Hospital
  73. Genetic profile mutation rpoB in clinical isolate of rifampicin-resistant Staphylococcus aureus
  74. Hematological side effect analysis of linezolid in MDR-TB patients with individual therapy
  75. Adverse drug reaction and its management in tuberculosis patients with multidrug resistance: a retrospective study
  76. Analysis of prophylactic antibiotic use and risk factor of postoperative infection in urological surgery patients
  77. Molecular docking studies of Nigella sativa L and Curcuma xanthorrhiza Roxb secondary metabolites against histamine N-methyltransferase with their ADMET prediction
  78. Prediction of compounds with antiosteoporosis activity in Chrysophyllum cainito L. leaves through in silico approach
  79. Phyllanthin and hypophyllanthin, the isolated compounds of Phyllanthus niruri inhibit protein receptor of corona virus (COVID-19) through in silico approach
  80. Cratoxylum sumatranum stem bark exhibited antimalarial activity by Lactate Dehydrogenase (LDH) assay
  81. Endophytic fungi inhabiting Physalis angulata L. plant: diversity, antioxidant, and antibacterial activities of their ethyl acetate extracts
  82. Exploration of several plants from Baung Forest on bone formation cell models
  83. In vitro antimalarial activity of Garcinia parvifolia Miq. Stem extracts and fractions on Plasmodium falciparum lactate dehydrogenase (LDH) assay
  84. Antioxidant and antiviral potency of Begonia medicinalis fractions
  85. Artocarpus sericicarpus stem bark contains antimalarial substances against Plasmodium falciparum
  86. Formulation and characterization of Eleutherine palmifolia extract-loaded self-nanoemulsifying drug delivery system (SNEDDS)
  87. Analytical method for the determination of curcumin entrapped in polymeric micellar powder using HPLC
  88. Challenges in the provision of natural medicines by community pharmacists in East Java Province, Indonesia
  89. In vitro and in silico analysis of phytochemical compounds of 96% ethanol extract of semanggi (Marsilea crenata Presl.) leaves as a bone formation agent
  90. Inhibitory activity of Urena lobata leaf extract on alpha-amylase and alpha-glucosidase: in vitro and in silico approach
  91. Case Report
  92. Effect of hydrocortisone on hypocorticolism caused by pituitary adenoma
https://doi.org/10.1515/jbcpp-2020-0433
Schlagwörter für diesen Artikel
A549 cancer cell; ADMET prediction; benzoxazines; molecular docking; synthesis

Artikel in diesem Heft

  1. Frontmatter
  2. Original Articles
  3. Cost of illness of diabetes mellitus in Indonesia: a systematic review
  4. Social media health interventions to improve diabetes mellitus patient outcome: a systematic review
  5. Developing pharmacokinetics–pharmacodynamics model of valproic acid syrup based on prediction of population pharmacokinetics parameter and seizure frequency in Indonesian pediatric epilepsy outpatients
  6. Acetylcholinesterase inhibitory activity of extract and fractions from the root of Rauvolfia serpentina(L.) Bth.ex Kurz
  7. Green tea and its active compound epigallocathechin-3-gallate (EGCG) inhibit neuronal apoptosis in a middle cerebral artery occlusion (MCAO) model
  8. The effects of quercetin on nicotine-induced reward effects in mice
  9. Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior
  10. Translation and cross-cultural adaption of an instrument measuring patient’s well-being under treatment for schizophrenia
  11. Quercetin promotes behavioral recovery and biomolecular changes of melanocortin-4 receptor in mice with ischemic stroke
  12. Knowledge and attitudes of healthcare professionals on prescribing errors
  13. Inhibition of Ras and STAT3 activity of 4-(tert-butyl)-N-carbamoylbenzamide as antiproliferative agent in HER2-expressing breast cancer cells
  14. Predicting the molecular mechanism of glucosamine in accelerating bone defect repair by stimulating osteogenic proteins
  15. Larvicidal toxicity and parasporal inclusion of native Bacillus thuringiensis BK5.2 against Aedes aegypti
  16. Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells
  17. Thymoquinone and its derivatives against breast cancer with HER2 positive: in silico studies of ADMET, docking and QSPR
  18. Assessment of patient understanding of their conventional cardiac medicines and herbal prepared/derived products: preliminary survey and interviews with selected community-dwelling elderly patients in the Philippines
  19. The development and validation of the health belief model questionnaire for measuring factors affecting adherence in the elderly with hypertension
  20. Analysis of the side effect of QTc interval prolongation in the bedaquiline regimen in drug resistant tuberculosis patients
  21. Shallot skin profilling, computational evaluation of physicochemical properties, ADMET, and molecular docking of its components against P2Y12 receptor
  22. Analysis of HMGB-1 level before and after providing atorvastatin standard therapy in coronary artery disease patients with type-2 diabetes mellitus compared to without type-2 diabetes mellitus
  23. Analysis of matrix metalloproteinase-9 levels among acute heart failure patients with ACE inhibitor therapy (Dr. Soetomo Regional General Hospital, Surabaya)
  24. The correlation between self-related adherence, asthma-related quality of life and control of asthma in adult patients
  25. Providing counseling through home pharmacy care (HPC) for hemodialysis patients with hypertension in lowering blood pressure
  26. Community knowledge and attitude in recognizing asthma symptoms and using medication for asthma attacks: a cross-sectional study
  27. A study of anticoagulant therapy in patients with coronary artery disease
  28. The association of FKBP5 polymorphism with asthma susceptibility in asthmatic patients
  29. Gastroprotective effect of fluvoxamine and ondansetron on stress-induced gastric ulcers in mice
  30. Osteoblast iron genes: real time PCR and microarray hybridization approach under hyperoxia
  31. Attenuation of hyperplasia in lung parenchymal and colonic epithelial cells in DMBA-induced cancer by administering Andrographis paniculata Nees extract using animal model
  32. N-nitrosodiethylamine induces inflammation of liver in mice
  33. AST/ALT levels, MDA, and liver histopathology of Echinometra mathaei ethanol extract on paracetamol-induced hepatotoxicity in rats
  34. Development, characterization, molecular docking, and in vivo skin penetration of coenzyme Q10 nanostructured lipid carriers using tristearin and stearyl alcohol for dermal delivery
  35. The effect of Camellia sinensis (green tea) with its active compound EGCG on neuronal cell necroptosis in Rattus norvegicus middle cerebral artery occlusion (MCAO) model
  36. Hepatoprotective effect of ethanolic extract of sugarcane (Saccharum officinarum Linn.) leaves
  37. Correlation between the exposure time to mobile devices and the prevalence of evaporative dry eyes as one of the symptoms of computer vision syndrome among Senior High School students in East Java, Indonesia
  38. The effect of various high-fat diet on liver histology in the development of NAFLD models in mice
  39. Fabrication and characterization of bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked by glutaraldehyde for bone regeneration
  40. Health related quality of life among postmenopausal woman with hormone responsive HER2− breast cancer in Indonesia
  41. Gender differences in the blood glucose type 2 diabetes patients with combination rapid and long acting insulin therapy
  42. Correlation of dietary iron intake and serum iron with thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels in adult hyperthyroid patients
  43. The effect of pillbox use and education by pharmacist toward medication adherence in diabetes mellitus patients in a Primary Health Care Center in Mataram
  44. Variation concentration effect of propyleneglycol, glycerin, and polyethyleneglycol 400 to physical properties and dissolution rate of loratadine liquisolid tablet
  45. Role of Centella asiatica and ceramide in skin barrier improvement: a double blind clinical trial of Indonesian batik workers
  46. Secondary metabolite and antipyretic effects of Maja (Crescentia cujete L.) in fever-induced mice
  47. Hydration effect on kidney function and serum electrolyte in children with tumor lysis syndrome (TLS) and risk of TLS
  48. Drug utilization study and cost analysis of adult β-thalassemia major patient therapy at Dr. Soetomo General Hospital Surabaya
  49. The role of hyperbaric oxygen to platelet aggregation in noninsulin-dependent diabetes mellitus (NIDDM)
  50. Cocrystal formation of loratadine-succinic acid and its improved solubility
  51. The role of chondroitin sulfate to bone healing indicators and compressive strength
  52. The effects of quercetin on the expression of SREBP-1c mRNA in high-fat diet-induced NAFLD in mice
  53. Analysis of stress ulcer prophylaxis drug regimentation in surgical patients
  54. The stability and irritability study of the chitosan–Aloe vera spray gel as wound healing
  55. Effectiveness of citicoline in pediatric patients with refractive amblyopia in Surabaya, East Java, Indonesia
  56. The thermodynamic study of p-methoxycinnamic acid inclusion complex formation, using β-cyclodextrin and hydroxypropyl-β-cyclodextrin
  57. The effect of chitosan type and drug-chitosan ratio on physical characteristics and release profile of ketoprofen microparticles prepared by spray drying
  58. The maximum dose and duration in the therapy single use methotrexate to achieve remission by rheumatoid arthritis patients through disease activity score 28 (DAS28)
  59. Knowledge, attitudes, and practices (KAP) towards COVID-19 among university students in Pakistan: a cross-sectional study
  60. The impact of glutaraldehyde on the characteristics of bovine hydroxyapatite-gelatin based bone scaffold as gentamicin delivery system
  61. Analysis of the use of antibiotics profile and factors of surgical site infections study on digestive and oncology surgeries
  62. Second internal transcribed spacer (ITS-2) as genetic marker for molecular characterization of Sarcoptes scabiei in rabbits from several areas of East Java, Indonesia
  63. Design of gossypetin derivatives based on naturally occurring flavonoid in Hibiscus sabdariffa and the molecular docking as antibacterial agents
  64. Discovery of new targeting agents against GAPDH receptor for antituberculosis drug delivery
  65. The effect of red passion fruit (Passiflora edulis Sims.) fermentation time on its activity against Extended Strain Methicillin-Resistant (ESBL) Escherichia coli and Methicillin-Resistant Staphylococcus aureus (MRSA)
  66. Antibiotic use on acute respiratory tract infection nonpneumonia and nonspecific diarrhea in Primary Health Care Centre in Banjarbaru City, South Kalimantan, Indonesia
  67. Screening of anti-HIV activities in ethanol extract and fractions from Ficus fistulosa leaves
  68. The characteristics of lactic acid bacteria isolated from fermented food as potential probiotics
  69. Profile of gyrA gene mutation in clinical isolate of levofloxacin resistant Escherichia coli
  70. Antimicrobial activity of Centella asiatica and Gigantochloa apus
  71. Drug-related problems of antibiotic use in gastroenteritis related to patient therapy outcomes at Universitas Gadjah Mada Hospital
  72. The impact of suitability of empirical antibiotics use on therapeutic outcome of respiratory tract infection patients at inpatient wards of Universitas Gadjah Mada Academic Hospital
  73. Genetic profile mutation rpoB in clinical isolate of rifampicin-resistant Staphylococcus aureus
  74. Hematological side effect analysis of linezolid in MDR-TB patients with individual therapy
  75. Adverse drug reaction and its management in tuberculosis patients with multidrug resistance: a retrospective study
  76. Analysis of prophylactic antibiotic use and risk factor of postoperative infection in urological surgery patients
  77. Molecular docking studies of Nigella sativa L and Curcuma xanthorrhiza Roxb secondary metabolites against histamine N-methyltransferase with their ADMET prediction
  78. Prediction of compounds with antiosteoporosis activity in Chrysophyllum cainito L. leaves through in silico approach
  79. Phyllanthin and hypophyllanthin, the isolated compounds of Phyllanthus niruri inhibit protein receptor of corona virus (COVID-19) through in silico approach
  80. Cratoxylum sumatranum stem bark exhibited antimalarial activity by Lactate Dehydrogenase (LDH) assay
  81. Endophytic fungi inhabiting Physalis angulata L. plant: diversity, antioxidant, and antibacterial activities of their ethyl acetate extracts
  82. Exploration of several plants from Baung Forest on bone formation cell models
  83. In vitro antimalarial activity of Garcinia parvifolia Miq. Stem extracts and fractions on Plasmodium falciparum lactate dehydrogenase (LDH) assay
  84. Antioxidant and antiviral potency of Begonia medicinalis fractions
  85. Artocarpus sericicarpus stem bark contains antimalarial substances against Plasmodium falciparum
  86. Formulation and characterization of Eleutherine palmifolia extract-loaded self-nanoemulsifying drug delivery system (SNEDDS)
  87. Analytical method for the determination of curcumin entrapped in polymeric micellar powder using HPLC
  88. Challenges in the provision of natural medicines by community pharmacists in East Java Province, Indonesia
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Heruntergeladen am 5.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2020-0433/html?lang=de
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