Abstract
Considering that some thiopyrimidines were previously reported as potential therapeutics, the present study achieved novel analogs of bioactive 2-substituted thiopyrimidines-4-(3H)-ones via base catalyzed alkylation reaction of 2-thiouracil using alkyl and aralkyl bromides. The title compounds were 2-(1-butylthio)pyrimidine-4(3H)-one (5a), 2-(2-butylthio)pyrimidine-4(3H)-one (5b), 2-(cyclohexylmethylthio)pyrimidine-4(3H)-one (5c), 2-(benzylthio)pyrimidine-4(3H)-one (5d) and 2-(1-adamantylthio)pyrimidine-4(3H)-one (5e). Bioactivity tests revealed that thiopyrimidines 5a, 5c, 5d and 5e exhibited antimicrobial activity. The thiopyrimidine-4-one (5c) showed complete inhibition against Streptococcus pyogenes and Branhamella catarrhalis as well as antifungal action against Candida albicans. Significantly, the 1-adamantylthiopyrimidine (5e) was shown to be the most potent cytotoxic compound against multidrug-resistant small cell lung cancer (H69AR). Their structure-activity relationships were discussed.
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Antifungal Agents / chemical synthesis
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacology*
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Antimalarials / chemical synthesis
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Antimalarials / chemistry
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Antimalarials / pharmacology*
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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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Candida albicans / drug effects
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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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Mice
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Microbial Sensitivity Tests
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Molecular Structure
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Moraxella catarrhalis / drug effects
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Parasitic Sensitivity Tests
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Plasmodium falciparum / drug effects
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Pyrimidinones / chemical synthesis
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Pyrimidinones / chemistry
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Pyrimidinones / pharmacology*
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Stereoisomerism
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Streptococcus pyogenes / drug effects
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Structure-Activity Relationship
Substances
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2-thiopyrimidine-4-one
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Anti-Bacterial Agents
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Antifungal Agents
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Antimalarials
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Antineoplastic Agents
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Pyrimidinones