Synthesis and antimycobacterial activity of prodrugs of indeno[2,1-c]quinoline derivatives

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

Anti-tuberculosis drugs

Indeno[2

1-c]quinoline

Prodrug approach

MABA assay

Mosmans MTT assay

MEDICINE

MEDICIN

Biology

Biologi

Publikations- och innehållstyp

ref (ämneskategori)

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