Synthesis and antimycobacterial activity of prodrugs of indeno[2,1-c]quinoline derivatives
2011 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 46, no 4, 1306-1324 p.Article in journal (Refereed) Published
Recently we have reported anti-TB properties of a new class of conformationally-constrained indeno[2,1-c]quinolines, which are although considerably active (MIC 0.39-0.78 mu g/mL) suffered from intense solubility problems. We thought of improving their bioavailability by prodrugs approach. Accordingly esters of the "Lead" indeno[2,1-c]quinolines 1,15 and 27 derivatives were synthesized and their prodrug nature at the physiological pH were confirmed. Prodrugs were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv by MABA assay to show that they have 2- to 4-fold improved anti-TB activities, increased aqueous solubility and superior selectivity index over their respective parent compounds. MIC of these prodrugs was in the range of <0.20-6.0 mu g/mL and in general, no cytotoxicity was observed in VERO cells.
Place, publisher, year, edition, pages
2011. Vol. 46, no 4, 1306-1324 p.
Anti-tuberculosis drugs, Indeno[2, 1-c]quinoline, Prodrug approach, MABA assay, Mosmans MTT assay
Medical and Health Sciences Biological Sciences
IdentifiersURN: urn:nbn:se:uu:diva-152645DOI: 10.1016/j.ejmech.2011.01.053ISI: 000289048400034PubMedID: 21334792OAI: oai:DiVA.org:uu-152645DiVA: diva2:413851