Bioactivity and molecular modelling of diphenylsulfides and diphenylselenides.
Bis(2-bromo-4,5-dimethoxyphenyl)sulfide (5) and bis(2-bromo-4,5-dimethoxyphenyl) selenide (7) have been shown to block cells in the G2/M phase of the cell cycle, whereas the debromo (4,6) equivalents do not. The biobromoselenide (7) is cytotoxic to tumour cells in vitro and has been shown to increase the mitotic index of treated cells. These biological effects are consistent with disruption of the mitotic apparatus. This agent does not inhibit microtubule assembly in vitro, but does bind to tubulin. Molecular modelling of these structures indicates that their spatial and electronic structures may make an important contribution to the biological activity.
Woods
J A
JA
CRC Department of Experimental Chemotherapy, Pateson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Hadfield
J A
JA
McGown
A T
AT
Fox
B W
BW
D000818:Animals; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018036:Selenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013816:Thermodynamics; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D018036:Selenium Compounds; D013440:Sulfides; D014404:Tubulin