Publication: Novel antimycobacterial C-21 amide derivatives of the antibiotic fusidic acid: Synthesis, pharmacological evaluation and rationalization of media-dependent activity using molecular docking studies in the binding site of human serum albumin
Dziwornu, G.A Kamunya, S Ntsabo, T Chibale, K
Dziwornu, G.A
Kamunya, S
Ntsabo, T
Chibale, K
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Abstract
Fusidic acid is a natural product antibiotic used clinically, primarily against staphylococcal infections. It has also exhibited antimycobacterial activity against Mycobacterium species, including Mycobacterium tuberculosis (Mtb). Novel C-21 fusidic acid amides were synthesized and evaluated for antimycobacterial activity in a drug repositioning approach for tuberculosis. The synthesized compounds exhibited good potency in MB7H9/CAS medium albeit showing low to no activity in MB7H9/ADC medium. The fusidic acid ethanamides were, generally, the most potent of the analogues evaluated for antimycobacterial activity (MIC90 < 10 μM) in the MB7H9/CAS medium.
The lack of activity in the MB7H9/ADC medium was supported by strong binding interactions in the fusidic acid binding site of the human serum albumin (HSA) protein. The most potent antimycobacterial analogue was the N-(4-sulfamoylbenzyl)fusidic acid amide (1.26) with an MIC90 value of 2.71 μM.
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Date
2019-04-18
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Royal Society of Chemistry
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Keywords
Pharmacology,Tuberculosis,Molecules
Citation
Dziwornu GA, Kamunya S, Ntsabo T, Chibale K. Novel antimycobacterial C-21 amide derivatives of the antibiotic fusidic acid: Synthesis, pharmacological evaluation and rationalization of media-dependent activity using molecular docking studies in the binding site of human serum albumin. MedChemComm. 2019 Apr 18;10(6):961-9. doi: 10.1039/c9md00161a