Bioorganic and Medicinal Chemistry Letters, volume 95, pages 129471

Synthesis and anti-tumor activities in human leukemia-derived cells of polyenylpyrroles with a methyl group at the conjugated polyene terminus

Tomoya Higashi ¹

Chihiro Yoshida ¹

Yoshifumi Hachiro ¹

Chihiro Nakata ^{2, 3}

Azusa Takechi ^{3, 4}

Takuya Yagi ^{2, 3}

Kazuya MIYASHITA ^{3, 5}

Nobuo Kitada ¹

Rika Obata ⁶

Takashi Hirano ⁶

Takahiko Hara ^{2, 3, 4}

Shojiro MAKI ¹

Show full list: 12 authors

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Center for Neuroscience and Biomedical Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu-shi, Tokyo 182-8585, Japan |

Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan |

Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan |

⁴

Graduate School of Science, Department of Biological Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan |

⁵

Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan |

⁶

Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu-shi, Tokyo 182-8585, Japan |

Publication type: Journal Article

Publication date: 2023-10-01

Elsevier

Journal: Bioorganic and Medicinal Chemistry Letters

scimago Q2

wos Q2

SJR: 0.508

CiteScore: 5.7

Impact factor: 2.5

ISSN: 0960894X, 14643405

DOI: 10.1016/j.bmcl.2023.129471

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Organic Chemistry

Drug Discovery

Biochemistry

Molecular Biology

Pharmaceutical Science

Clinical Biochemistry

Molecular Medicine

Abstract

To develop novel drugs for treating T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) which are highly malignant hematological tumors, a series of analogs having a polyenylpyrrole structure of natural compounds (rumbrin and auxarconjugatin B) were synthesized and investigated their structure-activity relationships (SAR) of in vitro anti-T-ALL and anti-AML activities. We obtained three findings: (1) introduction of a methyl group at the conjugated polyene terminus enhanced anti-T-ALL activity, (2) analogs with a 3-chloropyrrole moiety had even higher selectivity for T-ALL cells, and (3) some analogs were effective against AML-derived cells. Among the studied compounds, 3-chloro-2-(8-ethoxycarbonylnona-1,3,5,7-tetraenyl) pyrrole 4e was the most promising candidate of T-ALL- and AML-treating drug. This study provides useful structural information for designing novel drugs treating T-ALL and AML.