Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis candidates
European Journal of Medicinal Chemistry
School of Chemistry, University of KwaZulu-Natal, Durban, South Africa; School of Biochemistry, Genetics and Microbiology, University of KwaZulu-Natal, Durban, South Africa; Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa; School of Pharmacy and Pharmacology, University of KwaZulu-Natal, Durban, South Africa
As part of an ongoing project to develop highly potent anti-tuberculosis therapeutics, six SQ109 derivatives were synthesized and screened in vitro for their anti-tuberculosis activity against the ATCC strain H37Rv and the extensively drug-resistant clinical strain XDR 173. Compound 16 with an extended alkene chain was the most active against both strains of Mycobacterium tuberculosis within a MIC range of 0.5-0.25 μM. Compound 12 and SQ109 were potent within a MIC range of 1-0.5 μM, whilst compound 18 displayed an activity within the MIC range of 0.5-2 μM against both Mycobacterium tuberculosis strains. © 2010 Elsevier Masson SAS. All rights reserved.
n (2 adamantyl) n' geranylethylenediamine; n (3,7 dimethyloctyl) n' (1 adamantyl)ethane 1,2 diamine; n (3,7 dimethyloctyl) n' (2 adamantyl)ethane 1,2 diamine; n (3,7,11 trimethyldodecyl) n' (2 adamantyl)ethane 1,2 diamine; n farnesyl n' (2 adamantyl)ethane 1,2 diamine; n geranyl n' (1 adamantyl)ethane 1,2 diamine; tuberculostatic agent; unclassified drug; antimicrobial activity; article; bacterial strain; drug potency; drug resistant tuberculosis; drug screening; drug structure; drug synthesis; in vitro study; minimum inhibitory concentration; Mycobacterium tuberculosis; nonhuman; structure activity relation; Adamantane; Antitubercular Agents; Dose-Response Relationship, Drug; Ethylenediamines; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Stereoisomerism