Medicinal Chemistry Research

, Volume 27, Issue 2, pp 388–405 | Cite as

Antiplatelet activity, molecular docking and QSAR study of novel N′-arylmethylidene-3-methyl-1-phenyl-6-p-chlorophenyl-1H-pyrazolo[3,4-b] pyridine-4-carbohydrazides

  • Ayesha Ramzan
  • Sara Siddiqui
  • Ahmad Irfan
  • Abdullah G. Al-Sehemi
  • Aftab Ahmad
  • Francis Verpoort
  • Adeel H. Chughtai
  • Misbahul A. Khan
  • Munawar A. Munawar
  • Muhammad Asim Raza Basra
Original Research
  • 74 Downloads

Abstract

A series of novel N′-arylmethylidene-3-methyl-1-phenyl-6-p-chlorophenyl-1H-pyrazolo[3,4-b]pyridine-4-carbohydrazide (2a2t) has been synthesized from hydrazide (1). The structures of newly synthesized compounds were confirmed by FT-IR, EI-MS, 1H NMR and 13C NMR techniques. The title compounds were evaluated for antioxidant and antiplatelet aggregation effect induced by arachidonic acid (AA) and collagen. All the compounds have exhibited high antioxidant potential and antiplatelet activity but (2c, 2e, 2f, 2g, 2i, 2m, 2o and 2q) have revealed superlative antiplatelet activity. The molecular docking against cyclooxygenase-1 and 2 (COX-1 and COX-2) and quantitative structure-activity relationship (QSAR) were performed in describing their antiplatelet potential against AA and collagen along with antioxidant potential determined by ABTS, DPPH and iron chelating methods. The molecular docking study exhibited that compounds (2c, 2e, 2f, 2g, 2i, 2l, 2m, 2o and 2q) were found to be active against COX-1 while 2o compound also showed activity against COX-2. Compounds 2g and 2l were found to have higher energy stabilization values in comparison to Aspirin. Computational evaluations both molecular docking and QSAR are in good agreement with antiplatelet and antioxidant activities of the compounds (2a2t). All the compounds especially 2g, 2l, 2m might be promising antiplatelet agents and might be helpful in the synthesis of new drugs for the treatment of cardiovascular and anti-inflammatory diseases.

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Keywords

Acyl Hydrazone Density Functional Theory Electrostatic Potential̇ Physiochemical Properties 

Notes

Acknowledgements

We are thankful to Higher Education Commission of Pakistan for research funding Indigenous 5000 PhD fellowship Batch VII (PIN # 117-6703-PS7-083) and Ex-Supervisor Professor Dr. Riffat Parveen (Late) for her countless efforts. Professor Dr. Makshoof Athar, Director, Institute of Chemistry, University of the Punjab, Lahore for his support and providing facilities to carry on this research work. We are also thankful to University of Health Sciences, Lahore for providing the Elisa reader and platelet counter facility.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2053_MOESM1_ESM.docx (2.6 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Ayesha Ramzan
    • 1
  • Sara Siddiqui
    • 1
  • Ahmad Irfan
    • 2
    • 3
  • Abdullah G. Al-Sehemi
    • 2
    • 3
  • Aftab Ahmad
    • 4
  • Francis Verpoort
    • 5
  • Adeel H. Chughtai
    • 5
    • 6
  • Misbahul A. Khan
    • 1
    • 7
  • Munawar A. Munawar
    • 1
  • Muhammad Asim Raza Basra
    • 1
  1. 1.Institute of ChemistryUniversity of the PunjabLahorePakistan
  2. 2.Department of Chemistry, Faculty of ScienceKing Khalid UniversityAbhaSaudi Arabia
  3. 3.Research Center for Advanced Materials Science (RCAMS)King Khalid UniversityAbhaSaudi Arabia
  4. 4.Center of Excellence in Molecular BiologyUniversity of the PunjabLahorePakistan
  5. 5.Laboratory of Organometallics, Catalysis, and Ordered Materials, State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of TechnologyWuhanChina
  6. 6.Institute of Chemical SciencesBahauddin Zakariya UniversityMultanPakistan
  7. 7.Department of ChemistryThe Islamia University of BahawalpurBahawalpurPakistan

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