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海洋源生物中的雷尼替林型生物碱:合成化学、生物活性和结构修饰。

Renieramycin-type alkaloids from marine-derived organisms: Synthetic chemistry, biological activity and structural modification.

机构信息

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, And School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin, 541004, PR China.

出版信息

Eur J Med Chem. 2021 Jan 15;210:113092. doi: 10.1016/j.ejmech.2020.113092. Epub 2020 Dec 9.

Abstract

Marine natural products are known for their diverse chemical structures and extensive bioactivities. Renieramycins, the member of tetrahydroisoquinoline family of marine natural products, arouse interests because of their strong antitumor activities and similar structures to the first marine antitumor agent ecteinascidin-743, approved by the European Union. According to the literatures, researches on the pharmacological activities of renieramycins mainly focus on their antitumor activities. In addition, by structural modification, derivatives of renieramycins show stronger antiproliferative activity and less accidental necrosis activity on cells. Nevertheless, the difficulties in extraction and separation hinder their further development. Hence, the synthetic chemistry work of renieramycins plays a key role in their further development. In this review, currently reported researches on the synthetic chemistry, pharmacological activities and structural modification of renieramycins are summarized, which will benefit future drug development and innovation.

摘要

海洋天然产物以其多样的化学结构和广泛的生物活性而闻名。雷尼尔霉素是海洋天然产物中四氢异喹啉家族的成员,因其强烈的抗肿瘤活性和与第一个被欧盟批准的海洋抗肿瘤药物埃替巴肽相似的结构而引起关注。根据文献报道,雷尼尔霉素的药理学活性研究主要集中在其抗肿瘤活性上。此外,通过结构修饰,雷尼尔霉素的衍生物对细胞显示出更强的增殖抑制活性和更小的意外坏死活性。然而,提取和分离的困难阻碍了它们的进一步发展。因此,雷尼尔霉素的合成化学工作对其进一步发展起着关键作用。本文综述了雷尼尔霉素的合成化学、药理学活性和结构修饰的研究进展,这将有助于未来的药物开发和创新。

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