Abstract:
:The reduced activation of PPARs has a positive impact on cancer cell growth and viability in multiple preclinical tumor models, suggesting a new therapeutic potential for PPAR antagonists. In the present study, the benzothiazole amides 2a-g were synthesized and their activities on PPARs were investigated. Transactivation assay showed a moderate activity of the novel compounds as PPARα antagonists. Notably, in cellular assays they exhibited cytotoxicity in pancreatic, colorectal and paraganglioma cancer cells overexpressing PPARα. In particular, compound 2b showed the most remarkable inhibition of viability (greater than 90%) in two paraganglioma cell lines, with IC50 values in the low micromolar range. In addition, 2b markedly impaired colony formation capacity in the same cells. Taken together, these results show a relevant anti-proliferative potential of compound 2b, which appears particularly effective in paraganglioma, a rare tumor poorly responsive to chemotherapy.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Ammazzalorso A,De Lellis L,Florio R,Laghezza A,De Filippis B,Fantacuzzi M,Giampietro L,Maccallini C,Tortorella P,Veschi S,Loiodice F,Cama A,Amoroso Rdoi
10.1016/j.bmcl.2019.06.020subject
Has Abstractpub_date
2019-08-15 00:00:00pages
2302-2306issue
16eissn
0960-894Xissn
1464-3405pii
S0960-894X(19)30400-7journal_volume
29pub_type
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