Abstract
A new class of N-substituted amidino-1-hydroxybenzimidazole derivatives (15-24) were synthesized and evaluated for their in vitro cytotoxic activities against human leukemia cell lines, HL-60 and K562. The preliminary results showed that compounds 16, 20, 21 and 23 had moderate antitumor activity against HL-60 cell line. Further investigation on the mechanism of the observed cytotoxic effects demonstrated that compound 21 increased the expression of autophagic and apoptotic genes and induced apoptosis of HL-60 cells.
MeSH terms
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Amidines / chemical synthesis*
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Amidines / pharmacology*
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Apoptosis / genetics
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Autophagy / drug effects
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Autophagy / genetics
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / pharmacology*
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Neoplastic
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HL-60 Cells
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Humans
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K562 Cells
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Molecular Structure
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RNA, Messenger / metabolism
Substances
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Amidines
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Antineoplastic Agents
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Apoptosis Regulatory Proteins
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Benzimidazoles
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RNA, Messenger