Synthesis and X-ray crystal structures of selected ω-mercaptosulfones

BackgroundNovel therapeutic agents that selectively induce tumor cell death are urgently needed in the clinical management of cancers. Such agents would constitute effective adjuvant approaches to traditional chemotherapy regimens. Organosulfur compounds (OSCs), such as diallyl disulfide, have demonstrated anti-proliferative effects on cancer cells. We have previously shown that synthesized relatives of dysoxysulfone, a natural OSC derived from the Fijian medicinal plant, Dysoxylum richi, possess tumor-specific antiproliferative effects and are thus promising lead candidates.MethodsBecause our structure-activity analyses showed that regions flanking the disulfide bond mediated specificity, we synthesized 18 novel OSCs by structural modification of the most promising dysoxysulfone derivatives. These compounds were tested for anti-proliferative and apoptotic activity in both normal and leukemic cells.ResultsSix OSCs exhibited tumor-specific killing, having no effect on normal bone marrow, and are thus candidates for future toxicity studies. We then employed mRNA expression profiling to characterize the mechanisms by which different OSCs induce apoptosis. Using Gene Ontology analysis we show that each OSC altered a unique set of pathways, and that these differences could be partially rationalized from a transcription factor binding site analysis. For example, five compounds altered genes with a large enrichment of p53 binding sites in their promoter regions (p < 0.0001).ConclusionsTaken together, these data establish OSCs derivatized from dysoxysulfone as a novel group of compounds for development as anti-cancer agents.

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“…The mercaptan 1 was known [ 18 ]. The mercaptosulfone 2 was prepared from a symmetrical starting material as outlined in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

Characterization of the apoptotic response of human leukemia cells to organosulfur compounds

et al. 2010

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Asymmetric Synthesis of Nonracemic Primary Amines via Spiroborate-Catalyzed Reduction of Pure (E)- and (Z)-O-Benzyloximes: Applications toward the Synthesis of Calcimimetic Agents

Espinosa

Meléndez

et al. 2013

J. Org. Chem.

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Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogs employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described.

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α-Thiodisulfides: construction and biological activities

Langler

2008

Journal of Sulfur Chemistry

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Synthesis and X-ray crystal structures of selected ω-mercaptosulfones

Cited by 3 publications

References 21 publications

Characterization of the apoptotic response of human leukemia cells to organosulfur compounds

Characterization of the apoptotic response of human leukemia cells to organosulfur compounds

Asymmetric Synthesis of Nonracemic Primary Amines via Spiroborate-Catalyzed Reduction of Pure (E)- and (Z)-O-Benzyloximes: Applications toward the Synthesis of Calcimimetic Agents

α-Thiodisulfides: construction and biological activities

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