Synthesis of polyenylpyrrole derivatives with selective growth inhibitory activity against T-cell acute lymphoblastic leukemia cells.

Yoshida C

Yoshida C(1), Higashi T(1), Hachiro Y(1), Fujita Y(1), Yagi T(2), Takechi A(3), Nakata C(2), Miyashita K(4), Kitada N(1), Saito R(5), Obata R(6), Hirano T(6), Hara T(7), Maki SA(8).
Author information:
(1)Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan; Center for Neuroscience and Biomedical Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
(2)Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
(3)Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Graduate School of Science, Department of Biological Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan.
(4)Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
(5)Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan; School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
(6)Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
(7)Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Graduate School of Science, Department of Biological Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan.
(8)Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan; Center for Neuroscience and Biomedical Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan. Electronic address: [Email]

https://dx.doi.org/10.1016/j.bmcl.2021.127837

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.