Moon, Eun-Yi published the artcileBenzylamide sulindac analogues induce changes in cell shape, loss of microtubules and G2-M arrest in a chronic lymphocytic leukemia (CLL) cell line and apoptosis in primary CLL cells, Computed Properties of 59973-80-7, the publication is Cancer Research (2002), 62(20), 5711-5719, database is CAplus and MEDLINE.
Given our interest in cyclic nucleotide phosphodiesterase inhibitors in chronic lymphocytic leukemia (CLL), we studied the effects of sulindac sulfone (exisulind), a non-cyclooxygenase-inhibitory end metabolite of the NSAID sulindac that has been reported to inhibit cGMP phosphodiesterases. We focused on a novel benzylamide analog of sulindac sulfone, CP461, which is in clin. trials as a chemotherapeutic agent. As previously reported for colon carcinoma cell lines, we found that CP461 induced a rise in cGMP levels and blocked cell proliferation in the CLL cell line WSU-CLL. Surprisingly, however, cell cycle anal. revealed that CP461 caused G2-M arrest with an EC50 of 1.1 渭M. G2-M arrest was associated with phosphorylation of Bcl2 (but not BAD, Bax, or Bcl-XL): both of these end points were abrogated by treatment with a calcium chelator. Although CP461 induces p53 up-regulation, G2-M arrest and Bcl2 phosphorylation were independent of p53. Because microtubule-active drugs such as vincristine also induced G2-M arrest and Bcl2 phosphorylation in WSU-CLL, whereas the genotoxic drugs etoposide and doxorubicin did not, we examined the effect of CP461 on microtubules by indirect immunofluorescence microscopy. CP461 eliminated microtubules rapidly, with reduction detected within 30 min of drug treatment. CP461 also induced marked changes in cell shape. Neither sulindac sulfide (a cyclooxygenase inhibitor) nor sulindac sulfone induced G2-M arrest, Bcl2 phosphorylation, microtubule disassembly, or cell shape changes. Treatment with 30 渭M CP461 induced greater than 50% apoptosis in 10 of 10 primary CLL leukemic cell samples, whereas the same drug concentration had only marginal effects (14% apoptosis) on whole mononuclear cells. Our work demonstrates that addition of a benzylamide moiety to sulindac compounds results in markedly altered pharmacol. properties that may be of use in the therapy of lymphoid malignancies.
Cancer Research published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Computed Properties of 59973-80-7.
Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem