STUDY OF BINDING INTERACTIONS OF HUMAN CARBONIC ANHYDRASE XII

  • Harsh Barua Department of Pharmaceutical Chemistry, Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai, India
  • Nidhi Bhagat Department of Pharmaceutical Chemistry, Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai, India
  • (mrs.) M. P. Toraskar Department of Pharmaceutical Chemistry, Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai, India

Abstract

Objective: The present study was carried out to study the binding interactions of different N’-(substituted phenyl sulfonyl)-pyridine-2-carbohydrazide derivatives and N’-(substituted phenyl sulfonyl)-thiophene-2-carbohydrazide derivatives which were synthesized by senior students from research laboratory, with objective to explore the suitability of selected ligands for their binding affinity for the selected target.

Methods: Binding interactions of the selected ligands were studied using glide module of Schrodinger software using Maestro 10.1 interface. At the end of molecular docking studies, docking scores along with 2D and 3D binding interactions of these ligands were studied to evaluate the potency of ligands to act as selective human carbonic anhydrase (hCAXII) inhibitors in comparison with standard inhibitor Acetazolamide (AZA).

Results: Docking study on the ligands exhibited very similar conformation and binding interactions with hCAXII as that of standard. This suggests that selected ligands might possess significant binding affinity for hCAXII.

Conclusion: It can be concluded that the selected ligands have the potential to act as inhibitors of hCAXII.

Keywords: Molecular docking, Glide module, hCAXII, Acetazolamide

References

1. Supuran CT, Scozzafava A. Carbonic anhydrases as targets for medicinal chemistry. Bioorg Med Chem Lett 2007;15:4336–50.
2. Vullo D, Innocenti A, Nishimori I, Pastorek Jaromı́r, Scozzafava A, Pastoreková, et al. Carbonic anhydrase inhibitors. inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma Drugs? Bioorg Med Chem Lett 2005;15:963–9.
3. Durdagi S, Şentürk M, Ekinci D, Balaydın HT, Göksu S, Küfrevioğlu ÖI, et al. Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site. Bioorg Med Chem Lett 2011;19:1381–9.
4. Nordfors K, Haapasalo J, Korja M, Niemelä A, Laine J, Parkkila AK, et al. The tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a group of medulloblastomas and supratentorial primitive neuroectodermal tumours: an association of CA IX with poor prognosis. BMC Cancer 2010;10:148.
5. Alafeefy AM, Isik S, Abdel-Aziz HA, Ashour AE, Vullo D, Al-Jaber NA, Supuran CT. Carbonic anhydrase inhibitors: benzenesulfonamides incorporating cyanoacrylamide moieties are low nanomolar/subnanomolar inhibitors of the tumor-associated isoforms IX and XII. Bioorg Med Chem Lett 2013;21:1396–403.
6. Güzel-Akdemir Ö, Akdemir A, Isik S, Vullo D, Supuran CT. o-Benzenedisulfonimido–sulfonamides are potent inhibitors of the tumor-associated carbonic anhydrase isoforms CA IX and CA XII. Bioorg Med Chem Lett 2013;21:1386–91.
Statistics
243 Views | 3791 Downloads
How to Cite
Barua, H., N. Bhagat, and (mrs.) M. P. Toraskar. “STUDY OF BINDING INTERACTIONS OF HUMAN CARBONIC ANHYDRASE XII”. International Journal of Current Pharmaceutical Research, Vol. 9, no. 1, Dec. 2016, pp. 118-25, doi:10.22159/ijcpr.2017v9i1.16633.
Section
Original Article(s)