Synthesis and in vitro antiproliferative activity of new 11-aminoalkylamino-substituted chromeno[2,3-b]indoles.

Abstract

To search for new biological activities of the chromeno[2,3-b]indoles, the 5-oxa analog of the indolo[2,3-b]quinolines that are known to have a potent antitumor activity, a series of 11-amino derivatives with various substituents at the C-2 position were prepared. The synthesis of the chromeno[2,3-b]indole structure involves the cyclization of 2-phenoxy-3-indolecarboxylates 3, accessible from the indole-3-carboxylate 1 and phenols 2, producing the chromeno[2,3-b]indol-11(6H)-ones 4, which is followed by dehydroxychlorination with phosphorus oxychloride to afford the 11-chlorochromeno[2,3-b]indoles 5. The treatment of 5 with various amines produced the corresponding 11-aminated chromeno[2,3-b]indoles 6, while some of the 11-ω-aminoalkylamino derivatives 6 were transformed into the 11-ω-sulfonylaminoalkylamino derivatives 8. The antiproliferative activity of these 11-aminochromeno[2,3-b]indoles 6 and 8 in vitro were tested using MV4-11 (human leukemia), A549 (lung cancer), HCT116 (colon cancer), and the normal mice fibroblast (BALB/3T3) and their potencies were described.

• Authors: Wei Peng, Marta Świtalska, Li Wang, Zhen-Wu Mei, Yoshiki Edazawa, Cui-Qing Pang, Ibrahim El-Tantawy El-Sayed, Joanna Wietrzyk, Tsutomu Inokuchi
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 58 Pg. 441-51 (Dec 2012) ISSN: 1768-3254 [Electronic] France
• PMID: 23151321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzopyrans
• Indoles
• DNA

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• BALB 3T3 Cells
• Benzopyrans (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA (chemistry, drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Fibroblasts (drug effects)
• HCT116 Cells
• Humans
• Indoles (chemical synthesis, chemistry, pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Models, Molecular
• Molecular Structure
• Salmon
• Spermatozoa (cytology, drug effects)
• Structure-Activity Relationship