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Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies.
Bioorg Chem. 2017 06; 72:89-101.BC

Abstract

Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.

Authors+Show Affiliations

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Chemistry, Government College University Faisalabad, 38000, Pakistan.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Chemistry, University of Education Lahore, Campus Dera Ghazi Khan, Punjab, Pakistan.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, 42300, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam, 40450 Selangor D. E., Malaysia.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: khalid.khan@iccs.edu.PCSIR Laboratories Complex Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 214412, Saudi Arabia. Electronic address: iqbal.choudhary@iccs.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28390994

Citation

Iqbal, Sarosh, et al. "Carbohydrazones as New Class of Carbonic Anhydrase Inhibitors: Synthesis, Kinetics, and Ligand Docking Studies." Bioorganic Chemistry, vol. 72, 2017, pp. 89-101.
Iqbal S, Saleem M, Azim MK, et al. Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies. Bioorg Chem. 2017;72:89-101.
Iqbal, S., Saleem, M., Azim, M. K., Taha, M., Salar, U., Khan, K. M., Perveen, S., & Choudhary, M. I. (2017). Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies. Bioorganic Chemistry, 72, 89-101. https://doi.org/10.1016/j.bioorg.2017.03.014
Iqbal S, et al. Carbohydrazones as New Class of Carbonic Anhydrase Inhibitors: Synthesis, Kinetics, and Ligand Docking Studies. Bioorg Chem. 2017;72:89-101. PubMed PMID: 28390994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies. AU - Iqbal,Sarosh, AU - Saleem,Muhammad, AU - Azim,M Kamran, AU - Taha,Muhammad, AU - Salar,Uzma, AU - Khan,Khalid Mohammed, AU - Perveen,Shahnaz, AU - Choudhary,M Iqbal, Y1 - 2017/03/30/ PY - 2017/02/13/received PY - 2017/03/28/revised PY - 2017/03/28/accepted PY - 2017/4/10/pubmed PY - 2017/6/18/medline PY - 2017/4/10/entrez KW - Carbohydrazones KW - Carbonic anhydrase II inhibitors KW - Cheminformatic analysis KW - Kinetic studies KW - Ligand docking KW - bis-Schiff bases SP - 89 EP - 101 JF - Bioorganic chemistry JO - Bioorg. Chem. VL - 72 N2 - Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/28390994/Carbohydrazones_as_new_class_of_carbonic_anhydrase_inhibitors:_Synthesis_kinetics_and_ligand_docking_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(17)30089-5 DB - PRIME DP - Unbound Medicine ER -