2. Academic Validation
  3. Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis

Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis

  • Eur J Med Chem. 2019 Feb 1;163:840-852. doi: 10.1016/j.ejmech.2018.12.026.
Babita Aneja 1,  Nashrah Sharif Khan 2,  Parvez Khan 3,  Aarfa Queen 4,  Afzal Hussain 5,  Md Tabish Rehman 5,  Mohamed F Alajmi 5,  Hesham R El-Seedi 6,  Sher Ali 3,  Md Imtaiyaz Hassan 7,  Mohammad Abid 8
Affiliations

Affiliations

  • 1 Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India; Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
  • 2 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India; Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
  • 3 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
  • 4 Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
  • 5 Department of Pharmacognosy College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
  • 6 Pharmacognosy Group, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, 751 23, Uppsala, Sweden.
  • 7 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India. Electronic address: [email protected].
  • 8 Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India. Electronic address: [email protected].
PMID: 30579124 DOI: 10.1016/j.ejmech.2018.12.026
Abstract

Microtubule affinity-regulating kinase 4 (MARK4) is a potential drug target as the same is found to be over expressed in several types of cancers. In search of effective MARK4 inhibitors, we have synthesized and characterized Isatin-triazole hydrazones (9a-i) and evaluated their inhibitory potential. Of all the compounds, 9g showed better binding affinity and Enzyme inhibition potential in sub micromolar range. Human serum albumin (HSA) binding assay suggested an easy transportation of 9g in blood stream due to its binding affinity. In vitro Anticancer studies performed on MCF-7, MDA-MB-435s and HepG2 cells using 9g showed inhibition of cell proliferation and cell migration. Further, 9g induces Apoptosis in these cancerous cells, with IC50 values of 6.22, 9.94 and 8.14 μM, respectively. Putatively, 9g seems to cause oxidative stress resulting in Apoptosis. Functional assay of 9g with a panel of 26 kinases showed MARK4 specific profile. In conclusion, 9g seems to possess an effective inhibitory potential towards MARK4 adding an additional repertoire to Anticancer therapeutics.

Keywords

Apoptosis; Cell proliferation; Isatin-triazole hydrazones; Metastasis; Microtubule affinity-regulating kinase 4; Oxidative stress.

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