title: Synthesis and antitumor activity of novel benzimidazole-5-carboxylic acid derivatives and their transition metal complexes as topoisomerease II inhibitors.
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.
authors.affiliation: Division of Pharmaceutical and Drug Industries, Department of Chemistry of Natural and Microbial Products, National Research Center, Cairo 12311, Egypt. sh12galal@yahoo.com
authors.forename: Shadia A
authors.initials: SA
authors.lastname: Galal
authors.forename: Khaled H
authors.initials: KH
authors.lastname: Hegab
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Hashem
authors.forename: Nabil S
authors.initials: NS
authors.lastname: Youssef
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C470231:5-benzimidazolecarboxylic acid; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D004250:DNA Topoisomerases, Type II