Synthesis and antitumour activity of trimethylsilylpropyl substituted benzimidazoles. 2001

E Lukevics, and P Arsenyan, and I Shestakova, and I Domracheva, and A Nesterova, and O Pudova
Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006, Riga, Latvia. sinta@osi.lv

The quaternisation of N-substituted benzimidazoles by heating with various alkyl, allyl, propargyl and benzyl chlorides and bromides leads to the formation of benzimidazolinium salts. The interaction of N-monosubstituted benzimidazoles with various salts (CuCl2, ZnCl2, CoCl2, PdCl2 and AgNO3) yielded stable solid complexes. Potential cytotoxic activity of synthesised benzimidazolinium salts and benzimidazole metal complexes was tested in vitro on four monolayer tumour cell lines: MG-22A (mouse hepatoma), HT-1080 (human fibrosarcoma), B16 (mouse melanoma), Neuro 2A (mouse neuroblastoma) and normal mouse fibroblast cells. A preliminary analysis of the structure-activity relationship for the benzimidazole derivatives clearly indicates that the character of substituents in the benzimidazole ring has strong influence on the cytotoxic activity. The insertion of the silicon atom into the N-alkyl chain increases the cytotoxic activity of benzimidazolinium salts significantly, which show a very significant potency in vitro against all studied tumour cell lines, being particularly active in experiments with B16 (mouse melanoma). TD50 for the most active compounds are in the range 0.001-0.008 microg x ml(-1). Cytotoxicity of benzimidazole metal complexes (L2MX2) strongly depends on the metal nature. 1-(3-trimethylsilylpropyl)benzimidazole in dose 1 mg x kg(-1) inhibits carcinoma S-180 tumour growth by 62% (on ICR mice).

UI MeSH Term Description Entries
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001562 Benzimidazoles Compounds with a BENZENE fused to IMIDAZOLES.
D012509 Sarcoma A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. Sarcoma, Epithelioid,Sarcoma, Soft Tissue,Sarcoma, Spindle Cell,Epithelioid Sarcoma,Epithelioid Sarcomas,Sarcomas,Sarcomas, Epithelioid,Sarcomas, Soft Tissue,Sarcomas, Spindle Cell,Soft Tissue Sarcoma,Soft Tissue Sarcomas,Spindle Cell Sarcoma,Spindle Cell Sarcomas
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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