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o-Hydroxycinnamic derivatives as prospective anti-platelet candidates: in silico pharmacokinetic screening and evaluation of their binding sites on COX-1 and P2Y12 receptors

  • Kholis Amalia Nofianti and Juni Ekowati 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

The high prevalence of thrombotic abnormalities has become a major concern in the health sector. This is triggered by uncontrolled platelet aggregation, which causes complications and death. The problem becomes more complicated because of the undesirable side effects of the drugs currently in use, some of which have reportedly become resistant. This study aims to evaluate the potency of o-hydroxycinnamic acid derivatives (OCA1a–22a) and their pharmacokinetic properties and toxicity for them to be developed as new antiplatelet candidates.

Methods

In silico analysis of pharmacokinetics was carried out using pKCSM. Molecular docking of the compounds OCA 1a–22a was performed using the Molegro Virtual Docker. In silico evaluation of the potency of biological activity was done by measuring the bonding energy of each tested compound to the target receptor i.e. COX-1 and P2Y12, as the Moldock score (MDS).

Results

pKCSM analyses showed that more than 90% of OCA 1a–22a are absorbed through the intestine and distributed in plasma. Most tested compounds are not hepatotoxic, and none is mutagenic. An evaluation of the COX-1 receptor showed that OCA 2a–22a have lower binding energy compared to aspirin, which is the COX-1 inhibitor used today. So, it can be predicted that OCA 2–22a have stronger activity. Interactions with P2Y12 show lower MDS than aspirin, but slightly higher than ibuprofen, which is the standard ligand.

Conclusions

ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile prediction shows that OCA 1a–22a have the potential to be developed as oral preparations. OCA 1a–22a have strong potential to interact with COX-1 and P2Y12 receptors, so they are prospective anti-platelet candidates.

Keywords: anti-platelet; COX-1 inhibitor; Molegro Virtual Docker; P2Y12 inhibitor; pKCSM

  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.

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Received: 2019-11-01
Accepted: 2019-11-08
Published Online: 2019-12-19

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jbcpp-2019-0327
Keywords for this article
anti-platelet; COX-1 inhibitor; Molegro Virtual Docker; P2Y12 inhibitor; pKCSM

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
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  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
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