BO-0742, a derivative of AHMA and N-mustard, has selective toxicity to drug sensitive and drug resistant leukemia cells and solid tumors

Abstract This is a preclinical study of BO-0742, a derivative of 3-(9-acridinylamino)-5-hydroxymethyl-aniline (AHMA) and N-mustard, as an anti-cancer agent. MTS assays revealed a broad spectrum of anti-cancer activities in vitro , with the greatest cytotoxicity against leukemia and neuroblastoma inc...

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Bibliographic Details
Published in:Cancer letters 2009-04, Vol.276 (2), p.204-211
Main Authors: Lee, Chien-Hsin, Chou, Ting-Chao, Su, Tsann-Long, Yu, John, Shao, Li-En, Yu, Alice L
Format: Article
Language:English
Subjects:
Acridines - pharmacokinetics
Acridines - pharmacology
Aniline Compounds - pharmacokinetics
Aniline Compounds - pharmacology
Animals
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
ATP Binding Cassette Transporter, Sub-Family B
ATP-Binding Cassette, Sub-Family B, Member 1 - physiology
BO-0742
Bone marrow
Breast cancer
Cell growth
Cell Line, Tumor
Colonies & territories
Cytotoxicity
Deoxyribonucleic acid
Derivatives
DNA
Drug dosages
Drug Resistance, Neoplasm
Hematology, Oncology and Palliative Medicine
Hematopoietic Stem Cells - drug effects
Humans
Leukemia
Leukemia - drug therapy
Leukemia - pathology
Male
Mice
Multidrug Resistance-Associated Proteins - physiology
N-mustard
Neoplasms - drug therapy
Neoplasms - pathology
Nitrogen Mustard Compounds - pharmacology
Ovarian cancer
Pharmacokinetics
Plasma
Pre-clinical study
R&D
Research & development
Solid tumors
Toxicity
Tumors
Xenograft Model Antitumor Assays
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Summary:Abstract This is a preclinical study of BO-0742, a derivative of 3-(9-acridinylamino)-5-hydroxymethyl-aniline (AHMA) and N-mustard, as an anti-cancer agent. MTS assays revealed a broad spectrum of anti-cancer activities in vitro , with the greatest cytotoxicity against leukemia and neuroblastoma including those with drug resistant characteristics, and a good therapeutic index with leukemia being 10–40 times more sensitive to BO-0742 than hematopoietic progenitors. Administration of BO-0742 at an optimal dose schedule based on its pharmacokinetics significantly suppressed the growth of xenografts of human breast and ovarian cancers in mice. Thus, BO-0742 is a potent anti-cancer agent worthy of further clinical development.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2008.11.006