RRC ID 62197
Author Galal SA, Hegab KH, Hashem AM, Youssef NS.
Title Synthesis and antitumor activity of novel benzimidazole-5-carboxylic acid derivatives and their transition metal complexes as topoisomerease II inhibitors.
Journal Eur J Med Chem
Abstract N-aminomethyl-1H-benzimidazole-5-carboxylic acid derivatives 2-5 and the ligand, 1-(5 (or 6-)-carboxy-1H-benzimidazol-2-ylmethyl)pyridinium chloride (6; H2L1) have been synthesized. New benzimidazole complexes 7-9 of the ligand 6; H2L1 with Cu2+, Co2 and Zn2+ were prepared. The growth-inhibitory against a panel of 21 human cancer cell lines of the synthesized compounds 1-9 was studied. Compounds 6-9 showed potent growth-inhibitory activity against the studied cell lines. The correlation coefficients according to COMPARE analysis of the National Cancer Institute screening protocol showed that the pattern of the growth-inhibitory effect of the compounds 6-9 was similar to that of etoposide and doxorubicin but different from that of SN-38 and cisplatin. The topoisomerase II inhibitory activity of the tested compounds 6-9 was studied. Compounds 6 and 8 inhibited topoisomerase II activity at 10 times lower concentration than etoposide in relaxation assay.
Volume 45(12)
Pages 5685-91
Published 2010-12-1
DOI 10.1016/j.ejmech.2010.09.023
PII S0223-5234(10)00671-9
PMID 20884089
MeSH Animals Antineoplastic Agents / chemical synthesis Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Benzimidazoles / chemical synthesis Benzimidazoles / chemistry Benzimidazoles / pharmacology* Carboxylic Acids / chemical synthesis Carboxylic Acids / chemistry Carboxylic Acids / pharmacology* Cell Line, Tumor Cell Proliferation / drug effects DNA Topoisomerases, Type II / metabolism* Drug Screening Assays, Antitumor Enzyme Inhibitors / chemical synthesis Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology* Humans Mice Molecular Structure Organometallic Compounds / chemical synthesis Organometallic Compounds / chemistry Organometallic Compounds / pharmacology* Stereoisomerism Structure-Activity Relationship
IF 5.573
Human and Animal Cells HGC-27(RCB0500)