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 μg/mL) suffered from intense solubility problems. We thought of improving their bioavailability by prodrugs approach. Accordingl...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2011-04, Vol.46 (4), p.1306-1324
Main Authors: Upadhayaya, Ram Shankar, Shinde, Popat D., Kadam, Sandip A., Bawane, Amit N., Sayyed, Aftab Y., Kardile, Ramakant A., Gitay, Pallavi N., Lahore, Santosh V., Dixit, Shailesh S., Földesi, András, Chattopadhyaya, Jyoti
Format: Article
Language:English
Subjects:
1-c]quinoline
Amino Acids - chemistry
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - toxicity
Anti-tuberculosis drugs
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biologi
Biological and medical sciences
Biology
Cell Line
Humans
Hydrolysis
Hydrophobic and Hydrophilic Interactions
Indeno
Indeno[2,1- c]quinoline
MABA assay
Medical sciences
MEDICIN
MEDICINE
Microbial Sensitivity Tests
Mosmans MTT assay
Mycobacterium tuberculosis - drug effects
NATURAL SCIENCES
NATURVETENSKAP
Pharmacology. Drug treatments
Prodrug approach
Prodrugs - chemical synthesis
Prodrugs - metabolism
Prodrugs - pharmacology
Prodrugs - toxicity
Quinolines - metabolism
Solubility
Water - chemistry
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Summary: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 μg/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
ISSN:0223-5234
1768-3254
1768-3254
DOI:10.1016/j.ejmech.2011.01.053