Dziwornu, G.AKamunya, SNtsabo, TChibale, K2024-06-092024-06-092019-04-18Dziwornu 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/c9md00161ahttps://doi.org/10.1039/C9MD00161Ahttps://pubs.rsc.org/en/content/articlelanding/2019/md/c9md00161ahttps://hdl.handle.net/11288/596351Fusidic 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.enAttribution 3.0 United Stateshttp://creativecommons.org/licenses/by/3.0/us/PharmacologyTuberculosisMoleculesArticleMedChemComm