Vela Fátima, Ezzanad Abdellah, Hunter Alan Christy, Macías-Sánchez Antonio José, Hernández-Galán Rosario
Departamento de Química Orgánica and Instituto de Investigación en Biomoléculas [INBIO], Facultad de Ciencias, Universidad de Cádiz, Puerto Real, 11510 Cadiz, Spain.
School of Pharmacy, College of Science, University of Lincoln, Lincolns LN6 7DL, UK.
Pharmaceuticals (Basel). 2022 Jun 23;15(7):780. doi: 10.3390/ph15070780.
Lathyrane diterpenoids are one of the primary types of secondary metabolites present in the genus and one of the largest groups of diterpenes. They are characterized by having a highly oxygenated tricyclic system of 5, 11 and 3 members. These natural products and some synthetic derivatives have shown numerous interesting biological activities with clinical potential against various diseases, such as cytotoxic activity against cancer cell lines, multi-drug resistance reversal, antiviral properties, anti-inflammatory activity and their capability to induce proliferation or differentiation into neurons of neural progenitor cells. The structure of the lathyrane skeleton could be considered privileged because its framework is able to direct functional groups in a well-defined space. The favorable arrangement of these makes interaction possible with more than one target. This review aims to highlight the evidence of lathyranes as privileged structures in medicinal chemistry. Chemical structures of bioactive compounds, the evaluation of biological properties of natural and semisynthetic derivatives, and the exploration of the mechanisms of action as well as target identification and some aspects of their targeted delivery are discussed.
山黧豆烷二萜类化合物是该属中存在的主要次生代谢产物类型之一,也是最大的二萜类化合物群体之一。它们的特征是具有由5、11和3个成员组成的高度氧化的三环系统。这些天然产物和一些合成衍生物已显示出许多有趣的生物活性,具有针对各种疾病的临床潜力,例如对癌细胞系的细胞毒性活性、多药耐药逆转、抗病毒特性、抗炎活性以及它们诱导神经祖细胞增殖或分化为神经元的能力。山黧豆烷骨架的结构可以被认为是具有优势的,因为其框架能够在明确定义的空间中引导官能团。这些官能团的有利排列使得与多个靶点的相互作用成为可能。本综述旨在强调山黧豆烷类化合物作为药物化学中具有优势的结构的证据。讨论了生物活性化合物的化学结构、天然和半合成衍生物的生物学性质评估、作用机制的探索以及靶点鉴定及其靶向递送的一些方面。