Sulfonamides containing curcumin scaffold: Synthesis, characterization, carbonic anhydrase inhibition and molecular docking studies

Mahmood Ahmed; Muhammad Abdul Qadir; Abdul Hameed; Muhammad Nadeem Arshad; Abdullah M Asiri; Muhammad Muddassar

doi:10.1016/j.bioorg.2017.11.015

Sulfonamides containing curcumin scaffold: Synthesis, characterization, carbonic anhydrase inhibition and molecular docking studies

Bioorg Chem. 2018 Feb:76:218-227. doi: 10.1016/j.bioorg.2017.11.015. Epub 2017 Nov 20.

Authors

Mahmood Ahmed¹, Muhammad Abdul Qadir², Abdul Hameed³, Muhammad Nadeem Arshad⁴, Abdullah M Asiri⁴, Muhammad Muddassar⁵

Affiliations

¹ Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan. Electronic address: mahmoodresearchscholar@gmail.com.
² Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan.
³ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁴ Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence for Advanced Materials Research (CEAMR), Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad, Pakistan. Electronic address: mmuddassar@comsats.edu.pk.

PMID: 29190478
DOI: 10.1016/j.bioorg.2017.11.015

Abstract

Curcumin is a multi-functional pharmacologically safe natural agent with proven cytoprotective effects to healthy human cells. In this study, a new series of sulfonamides with curcumin scaffold were synthesized, characterized and investigated for their carbonic anhydrase isoenzyme I (human) and II (bovine) isoforms. The structures of newly synthesized compounds were described by IR, ¹H NMR and ¹³C NMR spectral data. Compound 14 showed the K_i value of 0.99 µM with highest inhibitory activity among all other synthesized compounds against hCA-I enzyme. Similarly enzyme kinetic studies of compound 14, 16 and 30 against bCAII enzyme showed Ki values of 0.71, 0.67 and 0.71 µM respectively. Our biological assays results showed that most of active compounds have similar inhibitory activities compared to standard acetazolamide drug. The molecular docking predicted binding modes showed that these compounds bind with hCA-1 enzyme in similar fashion.

Keywords: Carbonic anhydrase; Curcumin; Molecular docking; Sulfonamides.

Publication types

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

MeSH terms

Animals
Carbonic Anhydrase I / chemistry
Carbonic Anhydrase II / chemistry
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry*
Cattle
Curcumin / analogs & derivatives*
Curcumin / chemical synthesis
Enzyme Assays
Humans
Kinetics
Molecular Docking Simulation
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*

Substances

Carbonic Anhydrase Inhibitors
Sulfonamides
Carbonic Anhydrase I
Carbonic Anhydrase II
Curcumin