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Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2011 Apr 15; Vol. 19 (8), pp. 2541-8. Date of Electronic Publication: 2011 Mar 12. - Publication Year :
- 2011
-
Abstract
- A facile synthesis of model 4-oxopyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acids 9a-e was achieved via Stille arylation of 2-chloro-3-nitro-4-oxothieno[2,3-b]pyridine-5-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. Compounds 9a-c and 9e exhibited very high potency against Gram positive Bacillus subtilis and Bacillus megaterium at concentrations 0.000015-0.007 μg/mL. They also displayed excellent activity towards other Gram positive bacilli and staphylococci and Gram negative Haemophilus influenzae, being in most cases superior or equal to commercial fluoroquinolones. Both 9a and 9c were inhibitors of the DNA gyrase activity. As concerns antitumor properties, compounds 9b-e showed growth inhibition of MCF-7 breast tumor and A549 non-small cell lung cancer cells with IC(50) 1.6-2.8 μM and 2.6-6.9 μM, respectively, coupled with absence of cytotoxicity towards normal cells. These compounds are promising as dual acting chemotherapeutics.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Anti-Bacterial Agents pharmacology
Antineoplastic Agents pharmacology
Breast Neoplasms drug therapy
Breast Neoplasms pathology
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Dose-Response Relationship, Drug
Female
Gram-Negative Bacteria drug effects
Gram-Positive Bacteria drug effects
Humans
Topoisomerase II Inhibitors
Anti-Bacterial Agents chemical synthesis
Antineoplastic Agents chemical synthesis
Thienopyridines chemical synthesis
Thienopyridines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 19
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21458275
- Full Text :
- https://doi.org/10.1016/j.bmc.2011.03.018