title: Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents.
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.
authors: Chemistry Department, Faculty of Science, The University of Jordan, Amman, Jordan.
authors: Salah A
authors: SA
authors: Al-Trawneh
authors: Mustafa M
authors: MM
authors: El-Abadelah
authors: Jalal A
authors: JA
authors: Zahra
authors: Samir A
authors: SA
authors: Al-Taweel
authors: Franca
authors: F
authors: Zani
authors: Matteo
authors: M
authors: Incerti
authors: Andrea
authors: A
authors: Cavazzoni
authors: Paola
authors: P
authors: Vicini
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D058924:Thienopyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D058924:Thienopyridines; D059005:Topoisomerase II Inhibitors