Next Article in Journal
Complex Enzyme-Assisted Extraction Releases Antioxidative Phenolic Compositions from Guava Leaves
Next Article in Special Issue
New Metabolites of Coumarin Detected in Human Urine Using Ultra Performance Liquid Chromatography/Quadrupole-Time-of-Flight Tandem Mass Spectrometry
Previous Article in Journal
Nonempirical Simulations of Inhomogeneous Broadening of Electronic Transitions in Solution: Predicting Band Shapes in One- and Two-Photon Absorption Spectra of Chalcones
Previous Article in Special Issue
Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(10), 1644; doi:10.3390/molecules22101644

Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents

1
School of Pharmacy, Faculty of Natural Sciences, University of the Western Cape, Cape Town, Bellville 7550, South Africa
2
DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, Tygerberg 7505, South Africa
3
Medical Research Council/National Health Laboratory Service/University of Cape Town Molecular Mycobacteriology Research Unit, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, Rondebosch 7700, South Africa
4
Department of Medical Biosciences, University of the Western Cape, Cape Town, Bellville 7550, South Africa
*
Author to whom correspondence should be addressed.
Received: 15 September 2017 / Revised: 21 September 2017 / Accepted: 27 September 2017 / Published: 30 September 2017
(This article belongs to the Special Issue Versatile Coumarins)
View Full-Text   |   Download PDF [2736 KB, uploaded 30 September 2017]   |  

Abstract

A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at 50 µM. This prompted further exploration of all the 7-substituted coumarins in our library. Four compounds showed promising MIC99 values of 8.31–29.70 µM and 44.15–57.17 µM on M. tuberculosis H37Rv in independent assays using GAST-Fe and 7H9+OADC media, respectively. These compounds were found to bind to albumin, which may explain the variations in MIC between the two assays. Preliminary data showed that they were able to maintain their activity in fluoroquinolone resistant mycobacteria. Structure-activity relationships indicated that structural modification on position 4 and/or 7 of the coumarin scaffold could direct the selectivity towards either the inhibition of neuronal enzymes or the antimycobacterial effect. Moderate cytotoxicities were observed for these compounds and slight selectivity towards mycobacteria was indicated. Further neuroprotective assays showed significant neuroprotection for selected compounds irrespective of their neuronal enzyme inhibitory properties. These coumarin molecules are thus interesting lead compounds that may provide insight into the design of new antimicrobacterial and neuroprotective agents. View Full-Text
Keywords: coumarin; Mycobacterium tuberculosis; cholinesterase inhibitor; monoamine oxidase B inhibitor; structure-activity relationship; albumin binding; neuroprotection coumarin; Mycobacterium tuberculosis; cholinesterase inhibitor; monoamine oxidase B inhibitor; structure-activity relationship; albumin binding; neuroprotection
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Kapp, E.; Visser, H.; Sampson, S.L.; Malan, S.F.; Streicher, E.M.; Foka, G.B.; Warner, D.F.; Omoruyi, S.I.; Enogieru, A.B.; Ekpo, O.E.; Zindo, F.T.; Joubert, J. Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents. Molecules 2017, 22, 1644.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top