Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations
The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and ar...
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doaj-ca22ef8c721e4977b96985ecd43111ee2020-11-25T00:11:04ZengMDPI AGJournal of Clinical Medicine2077-03832018-08-017822610.3390/jcm7080226jcm7080226Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety InvestigationsSherif T. S. Hassan0Miroslava Šudomová1Kateřina Berchová-Bímová2Shanmugaraj Gowrishankar3Kannan R. R. Rengasamy4Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42 Brno, Czech RepublicMuseum of literature in Moravia, Klášter 1, 664 61 Rajhrad, Czech RepublicDepartment of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha 6-Suchdol, Czech RepublicDepartment of Biotechnology, Science Campus, Alagappa University, Karaikudi 630003, IndiaREEF Environmental Consultancy Services, #2 Kamaraj Street, S.P. Nagar, Puducherry 605 001, IndiaThe current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0–13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5'-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC50) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC50 value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure–activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections.http://www.mdpi.com/2077-0383/7/8/226psoromic acidarylamine N-acetyltransferaseUDP-galactopyranose mutaseantitubercular drugdrug resistancedrug design |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sherif T. S. Hassan Miroslava Šudomová Kateřina Berchová-Bímová Shanmugaraj Gowrishankar Kannan R. R. Rengasamy |
spellingShingle |
Sherif T. S. Hassan Miroslava Šudomová Kateřina Berchová-Bímová Shanmugaraj Gowrishankar Kannan R. R. Rengasamy Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations Journal of Clinical Medicine psoromic acid arylamine N-acetyltransferase UDP-galactopyranose mutase antitubercular drug drug resistance drug design |
author_facet |
Sherif T. S. Hassan Miroslava Šudomová Kateřina Berchová-Bímová Shanmugaraj Gowrishankar Kannan R. R. Rengasamy |
author_sort |
Sherif T. S. Hassan |
title |
Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations |
title_short |
Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations |
title_full |
Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations |
title_fullStr |
Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations |
title_full_unstemmed |
Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations |
title_sort |
antimycobacterial, enzyme inhibition, and molecular interaction studies of psoromic acid in mycobacterium tuberculosis: efficacy and safety investigations |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2018-08-01 |
description |
The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0–13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5'-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC50) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC50 value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure–activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections. |
topic |
psoromic acid arylamine N-acetyltransferase UDP-galactopyranose mutase antitubercular drug drug resistance drug design |
url |
http://www.mdpi.com/2077-0383/7/8/226 |
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