Abstract
A series of Mannich bases having piperidine moiety were reacted with 2-mercaptoethanol, leading to 1-aryl-3-piperidine-4-yl-1-propanone hydrochlorides. The cytotoxicity and carbonic anhydrase inhibitory activities of these new compounds were evaluated. Among the compounds, only one derivative, nitro substituent bearing EU9, showed an effective cytotoxicity, although weak tumor specificity against human oral malignant versus nonmalignant cells. The compound induced apoptosis in HSC-2 oral squamous cell carcinoma cells, but not in human gingival fibroblast. Chemical modifications of this lead are thus necessary to further investigate it as a drug candidate and to obtain compounds with a better activity profile.
Keywords:
Carbonic anhydrase inhibition; PARP; cytotoxicity; thiol addition.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Carbonic Anhydrase I / antagonists & inhibitors*
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Carbonic Anhydrase I / metabolism
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Carbonic Anhydrase II / antagonists & inhibitors*
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Carbonic Anhydrase II / metabolism
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Carbonic Anhydrase Inhibitors / chemical synthesis
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Carbonic Anhydrase Inhibitors / chemistry
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Carbonic Anhydrase Inhibitors / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Molecular Structure
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Propane / chemical synthesis
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Propane / chemistry
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Propane / pharmacology*
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Structure-Activity Relationship
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Sulfhydryl Compounds / chemical synthesis
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / pharmacology*
Substances
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Antineoplastic Agents
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Carbonic Anhydrase Inhibitors
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Isoenzymes
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Sulfhydryl Compounds
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Carbonic Anhydrase I
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Carbonic Anhydrase II
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Propane