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Oxindole-based chalcones: synthesis and their activity against glycation of proteins

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Abstract

Diabetes mellitus, a metabolic disorder, is characterized by a substantial hyperglycaemia. Prevalence of hyperglycaemia for longer period of time can cause nonenzymatic condensation of sugar in blood with amino group of protein and give rise to advanced glycation end products (AGEs). AGEs play a major role in the onset of late diabetic complications including diabetic retinopathy, nephropathy, neuropathy and cardiovascular diseases. There is a need to establish potential therapeutic regimens that can effectively inhibit the formation of AGEs. To this end a series of novel oxindole-based chalcones have been investigated for their antiglycation potential. Analogues 1 (IC50 = 155.22 ± 2.98 µM), 3 (IC50 = 195.95 ± 0.43 µM), 4 (IC50 = 289.47 ± 2.47 µM), 5 (IC50 = 222.44 ± 4.03 µM), 7 (IC50 = 251.27 ± 2.80 µM), and 20 (224.23 ± 1.93 µM) showed potent inhibitory activity against glycation compared to the reference Rutin (IC50 = 294.5 ± 1.5 µM). These results reveal that multiple hydroxyl substituents and their position on the aromatic ring play a key role in inhibitory effect due to their hydrogen bonding potential. The study also reveals the influence of substituents on the binding capabilities and in turn inhibitory potential of different analogues.

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Authors and Affiliations

  1. Department of Chemistry, COMSATS University Islamabad Abbottabad Campus, Abbottabad, Pakistan

    Ayesha Khan & Umar Farooq

  2. Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman

    Ajmal Khan, Sobia Ahsan Halim & Ahmed Al-Harrasi

  3. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, PO Box 1982, Dammam, 31441, Saudi Arabia

    Muhammad Taha

  4. Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor D.E., Malaysia

    Syed Adnan Ali Shah

  5. Faculty of Applied Science, UiTM Shah Alam, 40450, Shah Alam, Selangor D.E., Malaysia

    Syed Adnan Ali Shah

  6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Federal Urdu University of Arts, Science and Technology, Karachi, Pakistan

    Arfa Akram

  7. Department of Biological Sciences and Chemistry, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman

    Mohammed Ziauddin Khan

  8. Department of Chemistry, Shaheed Benazir Bhutto University Sheringal, Sheringal Dir Upper, Pakistan

    Abdul Khaliq Jan

Authors
  1. Ayesha Khan
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  2. Ajmal Khan
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  3. Umar Farooq
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  4. Muhammad Taha
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  5. Syed Adnan Ali Shah
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  6. Sobia Ahsan Halim
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  7. Arfa Akram
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  8. Mohammed Ziauddin Khan
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  9. Abdul Khaliq Jan
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  10. Ahmed Al-Harrasi
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Correspondence to Ajmal Khan, Umar Farooq or Ahmed Al-Harrasi.

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Khan, A., Khan, A., Farooq, U. et al. Oxindole-based chalcones: synthesis and their activity against glycation of proteins. Med Chem Res 28, 900–906 (2019). https://doi.org/10.1007/s00044-019-02345-1

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  • DOI: https://doi.org/10.1007/s00044-019-02345-1

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