| Literature DB >> 18226429 |
Lauren Lee1, Ryan Davis, Jenna Vanderham, Patrice Hills, Hilary Mackay, Toni Brown, Susan L Mooberry, Moses Lee.
Abstract
Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50<1 microM for L1210 and <10 microM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 microM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity.Entities:
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Year: 2007 PMID： 18226429 DOI： 10.1016/j.ejmech.2007.11.030
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514