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Title
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1,4-diarylpiperazines and analogs as anti-tubercular agents : synthesis and biological evaluation
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Author
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Abstract
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| Despite progress in modern chemotherapy to combat tuberculosis, the causative pathogen Mycobacterium tuberculosis (M.tb.) is far from eradicated. Bacillary resistance to anti-mycobacterial agents, bacillary persistence and human immunodeficiency virus (HIV) co-infection hamper current drug treatment to completely cure the infection, generating a constant demand for novel drug candidates to tackle these problems. A small library of novel heterocyclic compounds was screened in a rapid luminometric in vitro assay against the laboratory M.tb. strain H37Rv. A group of amidines was found to have the highest potency and was further evaluated for acute toxicity against C3A hepatocytes. Next, the most promising compounds were evaluated for activity against a multi-drug resistant clinical isolate. The group of amidines was also tested for their ability to kill intracellular M.tb. residing in mouse J774A.1 macrophages. Finally, we report on a correlation between the structural differences of the compounds and their anti-mycobacterial activity. |
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Language
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English
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Source (journal)
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European journal of medicinal chemistry. - Paris, 1974, currens
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Publication
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Paris
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2012
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ISSN
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0223-5234
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DOI
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10.1016/J.EJMECH.2011.12.035
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Volume/pages
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49
(2012)
, p. 95-101
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ISI
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000302033300009
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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