A diaryl sulfide, sulfoxide, and sulfone bearing structural similarities to combretastatin A-4.
Studies examining various spacer groups that link the two aromatic rings of combretastatin A-4 (CA4) have shown that the biological activity of analogs does not require the cis-stilbene configuration of CA4. Oxygen or nitrogen, carbonyl, methylene and ethylene spacers, for example, are present in CA4 analogs that show good activity. Up to now sulfur was not tested for this purpose. In this article we describe the synthesis of sulfide, sulfoxide and sulfone spacers between two aromatic rings comparable to those of CA4. We also compared them with CA4 for inhibitory effects on cell growth, tubulin polymerization, and the binding of [(3)H]colchicine to tubulin. We found that the sulfide is highly active and may be a lead compound for the preparation of antitumor compounds.
Barbosa
Euzébio G
EG
Universidade Federal de Mato Grosso do Sul, Departamento de Química-CCET, Laboratório LP4, CP 549, 79070-900 Campo Grande (MS), Brazil.
Bega
Luis A S
LA
Beatriz
Adilson
A
Sarkar
Taradas
T
Hamel
Ernest
E
do Amaral
Marcos S
MS
de Lima
Dênis Pires
DP
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry*; D013450:Sulfones / Q000737:chemistry*; D013454:Sulfoxides / Q000737:chemistry*; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D013267:Stilbenes; D013440:Sulfides; D013450:Sulfones; D013454:Sulfoxides; D014404:Tubulin; C058728:fosbretabulin; D003078:Colchicine