Synthesis of novel benzothiazole amides: Evaluation of PPAR activity and anti-proliferative effects in paraganglioma, pancreatic and colorectal cancer cell lines

被引：18

作者：

Ammazzalorso, Alessandra ^{[1
]}

De Lellis, Laura ^{[2
,3
]}

Florio, Rosalba ^{[2
]}

Laghezza, Antonio ^{[4
]}

De Filippis, Barbara ^{[1
]}

Fantacuzzi, Marialuigia ^{[1
]}

Giampietro, Letizia ^{[1
]}

Maccallini, Cristina ^{[1
]}

Tortorella, Paolo ^{[4
]}

Veschi, Serena ^{[2
]}

Loiodice, Fulvio ^{[4
]}

Cama, Alessandro ^{[2
,3
]}

Amoroso, Rosa ^{[1
]}

机构：

[1] Univ G dAnnunzio, Unita Chim Farmaceut, Dipartimento Farm, Chieti, Italy

[2] Univ G dAnnunzio, Unita Patol Gen, Dipartimento Farm, Chieti, Italy

[3] Univ G dAnnunzio, Aging Res Ctr CeSI, Chieti, Italy

[4] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, Via Orabona 4, I-70126 Bari, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 16期

关键词：

PPAR antagonists; Benzothiazoles; Amides; Anti-proliferative; Paraganglioma; Cytotoxicity; IN-VITRO; PEROXISOME; PROLIFERATION; FAMILY;

D O I：

10.1016/j.bmcl.2019.06.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 PPAR alpha antagonists. Notably, in cellular assays they exhibited cytotoxicity in pancreatic, colorectal and paraganglioma cancer cells overexpressing PPAR alpha. 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.

引用

页码：2302 / 2306

页数：5

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