Medicinal Chemistry Research

, Volume 26, Issue 7, pp 1397–1404 | Cite as

6-Substituted nicotinic acid analogues, potent inhibitors of CAIII, used as therapeutic candidates in hyperlipidemia and cancer

  • Haneen K. Mohammad
  • Muhammed H. Alzweiri
  • Mohammad A. Khanfar
  • Yusuf M. Al-Hiari
Original Research
  • 133 Downloads

Abstract

Nicotinic acid has been reported as a potential inhibitor of carbonic anhydrase III enzyme. Carbonic anhydrase III (CAIII) is an emerging new pharmacological target for the management of dyslipidemia and cancer progression. The activity of 6-substituted nicotinic acid analogs against carbonic anhydrase III was studied using a size-exclusion chromatography. The appearance of concentration-dependent vacancy peak was indicative of binding with CAIII. Chromatographic and docking studies revealed that the carboxylic acid of ligand is essential for binding via coordinate bond formation with Zn+2 ion in the enzyme active site. Moreover, the presence of a hydrophobic group, containing a hydrogen bond acceptor, at position 6 of the pyridine improves activity, e.g., 6-(hexyloxy) pyridine-3-carboxylic acid (Ki = 41.6 µM). Utilizing the weak esterase activity of CAIII, the inhibitory mode of 6-substituted nicotinic acid was confirmed.

Keywords

Nicotinic acid QSAR Carbonic anhydrase Esterase 

Notes

Acknowledgements

Part of this research was conducted during the sabbatical year granted to Dr. Muhammed Alzweiri by the University of Jordan in the academic year 2015/2016.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Haneen K. Mohammad
    • 1
  • Muhammed H. Alzweiri
    • 1
  • Mohammad A. Khanfar
    • 1
  • Yusuf M. Al-Hiari
    • 1
  1. 1.Department of Pharmaceutical Sciences, Faculty of PharmacyThe University of JordanAmmanJordan

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