Synthesis of polyenylpyrrole derivatives with selective growth inhibitory activity against T-cell acute lymphoblastic leukemia cells. (1st April 2021)

• Record Type: Journal Article
• Authors: Yoshida, Chihiro; Higashi, Tomoya; Hachiro, Yoshifumi; Fujita, Yuki; Yagi, Takuya; Takechi, Azusa; Nakata, Chihiro; Miyashita, Kazuya; Kitada, Nobuo; Saito, Ryohei; Obata, Rika; Hirano, Takashi; Hara, Takahiko; Maki, Shojiro A.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 37(2021)
• Publication Date: 2021-04-01
• Subjects: T-ALL -- Structure-activity relationships -- Inhibitor -- Rumbrin -- Auxarconjugatin-B; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.127837
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a hardly curable disease with a high relapse rate. 20 analogs were synthesized based on the structures of two kinds of fungi-derived polyenylpyrrole products (rumbrin (1 ) and auxarconjugatin-B (2 )) to suppress the growth of T-ALL-derived cell line CCRF-CEM and tested for growth-inhibiting activity. The octatetraenylpyrrole analog gave an IC50 of 0.27 μM in CCRF-CEM cells, while it did not affect Burkitt lymphoma-derived cell line Raji and the cervical cancer cell line HeLa, or the oral cancer cell line HSC-3 (IC50 > 10 μM). This compound will be a promising compound for developing T-ALL-specific drugs.