具有dna结合活性和细胞毒性的新型吡咯苯二氮卓（PBD） c1取代单体和二聚体的合成。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-01-06 DOI:10.1016/j.bmcl.2025.130095

George Procopiou, Paul J.M. Jackson, Paolo Andriollo, Md. Mahbub Hasan, Nicolas Veillard, Khondaker Miraz Rahman, David E. Thurston

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引用次数: 0

摘要

吡咯苯二氮卓类（PBDs）代表了一类主要的序列选择性dna烷基化分子，其中一个例子是，其二聚体dna交联形式被用作抗癌抗体药物偶联物（ADC） loncastuximab tesirine-lpyl的有效载荷。迄今为止，PBD类似物已经在三环骨架的每个位置上产生取代基，除了c1位置。我们在此报道了首次合成c1取代的PBD单体和二聚体，两者都具有dna结合活性和癌细胞毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Synthesis of novel pyrrolobenzodiazepine (PBD) C1-substituted monomers and dimers with DNA-binding activity and cytotoxicity

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Synthesis of novel pyrrolobenzodiazepine (PBD) C1-substituted monomers and dimers with DNA-binding activity and cytotoxicity

The pyrrolobenzodiazepines (PBDs) represent a major class of sequence-selective DNA-alkylating molecules, one example of which, in its dimeric DNA-cross-linking form, is employed as the payload in the anticancer Antibody Drug Conjugate (ADC) loncastuximab tesirine-lpyl. To date, PBD analogues have been produced with substituents at every position of the tricyclic skeleton except the C1-position. We report here the first synthesis of a C1-subsitituted PBD monomer and dimer, both of which possess DNA-binding activity and cytotoxicity in a cancer cell line.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.