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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

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Abstract

A series of novel N′-arylmethylidene-3-methyl-1-phenyl-6-p-chlorophenyl-1H-pyrazolo[3,4-b]pyridine-4-carbohydrazide (2a–2t) 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 (2a–2t). 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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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.

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Authors and Affiliations

  1. Institute of Chemistry, University of the Punjab, Lahore, 54590, Pakistan

    Ayesha Ramzan, Sara Siddiqui, Misbahul A. Khan, Munawar A. Munawar & Muhammad Asim Raza Basra

  2. Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia

    Ahmad Irfan & Abdullah G. Al-Sehemi

  3. Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia

    Ahmad Irfan & Abdullah G. Al-Sehemi

  4. Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

    Aftab Ahmad

  5. Laboratory of Organometallics, Catalysis, and Ordered Materials, State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, 430070, China

    Francis Verpoort & Adeel H. Chughtai

  6. Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Adeel H. Chughtai

  7. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

    Misbahul A. Khan

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  1. Ayesha Ramzan
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  2. Sara Siddiqui
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  3. Ahmad Irfan
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  4. Abdullah G. Al-Sehemi
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  5. Aftab Ahmad
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  6. Francis Verpoort
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  7. Adeel H. Chughtai
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  8. Misbahul A. Khan
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  9. Munawar A. Munawar
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  10. Muhammad Asim Raza Basra
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Correspondence to Misbahul A. Khan, Munawar A. Munawar or Muhammad Asim Raza Basra.

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Ramzan, A., Siddiqui, S., Irfan, A. et al. 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. Med Chem Res 27, 388–405 (2018). https://doi.org/10.1007/s00044-017-2053-0

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