Biological Evaluation of a Potential Anticancer Agent Methyl N-[5-(3'-Iodobenzoyl)-1H-Benzimidazol-2-yl]Carbamate.
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| Abstract |
Background: Resistance of cancer to chemo- and radiotherapy remains a major clinical problem. This study contributes to the ongoing search for agents that can bypass this resistance by developing a novel antimitotic theranostic. Materials and Methods: Methyl N-[5-(3'-iodobenzoyl)-1H-benzimidazol-2-yl]carbamates 1 and 2 were synthesized from a common precursor 3 or its 3'-stannylated derivative. The cytotoxicity of compound 1 was evaluated in several neuroblastoma and glioblastoma cell lines and in the NCI 60-cell assay. Biodistribution was conducted in mice after oral administration of compound 2 to determine tissue and brain uptake. Result: Lethal concentrations (LC50s) of compound 1 in neuroblastoma and glioblastoma are >15 × lower compared with compound 3, a drug currently tested in clinical studies in pediatric and adult brain tumors. Growth inhibition concentrations (GI50) are in the nanomolar range in 60 cancer cell lines. When compound 1 is combined with a 4-Gy dose of radiation, <0.5% of cells retain their reproductive integrity. Increased hydrophobicity of new agents greatly enhances their brain uptake after oral administration. Conclusions: Compound 1 is potently cytotoxic in a wide range of human cancer cell lines. Its structure allows incorporation of imaging and therapeutic radionuclides. It is therefore expected that compound 1 can be developed into a novel theranostic modality across a wide range of malignancies.
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| Authors | Zbigniew P Kortylewicz, Don W Coulter, Janina Baranowska-Kortylewicz |
| Journal | Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 35 Issue 1 Pg. 16-25 (Feb 2020) ISSN: 1557-8852 [Electronic] United States |
| PMID | 31687840 (Publication Type: Journal Article) |
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