Barrera-Vázquez Oscar Salvador, Gómez-Verjan Juan Carlos, Magos-Guerrero Gil Alfonso
Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico.
Dirección de Investigación, Instituto Nacional de Geriatría, Mexico City 10200, Mexico.
Biomolecules. 2021 Mar 22;11(3):467. doi: 10.3390/biom11030467.
Cellular senescence is a cellular condition that involves significant changes in gene expression and the arrest of cell proliferation. Recently, it has been suggested in experimental models that the elimination of senescent cells with pharmacological methods delays, prevents, and improves multiple adverse outcomes related to age. In this sense, the so-called senoylitic compounds are a class of drugs that selectively eliminates senescent cells (SCs) and that could be used in order to delay such adverse outcomes. Interestingly, the first senolytic drug (navitoclax) was discovered by using chemoinformatic and network analyses. Thus, in the present study, we searched for novel senolytic compounds through the use of chemoinformatic tools (fingerprinting and network pharmacology) over different chemical databases (InflamNat and BIOFACQUIM) coming from natural products (NPs) that have proven to be quite remarkable for drug development. As a result of screening, we obtained three molecules (hinokitiol, preussomerin C, and tanshinone I) that could be considered senolytic compound candidates since they share similarities in structure with senolytic leads (tunicamycin, ginsenoside Rb1, ABT 737, rapamycin, navitoclax, timosaponin A-III, digoxin, roxithromycin, and azithromycin) and targets involved in senescence pathways with potential use in the treatment of age-related diseases.
细胞衰老一种细胞状态，涉及基因表达的显著变化和细胞增殖的停滞。最近，实验模型表明，用药理学方法清除衰老细胞可延缓、预防和改善与衰老相关的多种不良后果。从这个意义上说，所谓的衰老细胞裂解化合物是一类能选择性清除衰老细胞（SCs）的药物，可用于延缓此类不良后果。有趣的是，第一种衰老细胞裂解药物（navitoclax）是通过化学信息学和网络分析发现的。因此，在本研究中，我们利用化学信息学工具（指纹识别和网络药理学）在来自天然产物（NPs）的不同化学数据库（InflamNat和BIOFACQUIM）中搜索新型衰老细胞裂解化合物，这些天然产物已被证明在药物开发方面相当出色。筛选结果是，我们获得了三种分子（扁柏酚、前乌苏门菌素C和丹参酮I），它们可被视为衰老细胞裂解化合物候选物，因为它们在结构上与衰老细胞裂解先导物（衣霉素、人参皂苷Rb1、ABT 737、雷帕霉素、navitoclax、知母皂苷A-III、地高辛、罗红霉素和阿奇霉素）相似，且与衰老途径中的靶点有关，可能用于治疗与年龄相关的疾病。
