Chemoinformatic Screening for the Selection of Potential Senolytic Compounds from Natural Products

Abstract

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.

Progress and Impact of Latin American Natural Product Databases

“…The elimination of senescent cells delays, prevents, and improves multiple adverse outcomes related to age. Through the use of chemoinformatics tools (fingerprinting and network pharmacology), and employing two NP databases, InflamNat and BIOFACQUIM, three senolytic compounds were identified [ 153 ].…”

Molecular Mechanism of Tanshinone against Prostate Cancer

“…This laboratory evidence shows that Tanshinone can inhibit mTOR-mediated tumor malignant behavior in prostate cancer cells by regulating the expression and phosphorylation of upstream and downstream protein molecules of the mTOR-mediated signaling pathway or by regulating other molecular pathways with obvious crosstalk with mTOR. It is worth noting that although Tanshinone is similar to rapamycin in structure, the regulation of mTOR does not directly inhibit the synthesis of mTOR like rapamycin, which means that Tanshinone has fewer side effects on normal tissue and is safer [ 163 , 164 ]. In short, Tanshinone has a significant inhibitory effect on prostate cancer.…”

Progress and Impact of Latin American Natural Product Databases

“…The elimination of senescent cells delays, prevents, and improves multiple adverse outcomes related to age. Through the use of chemoinformatics tools (fingerprinting and network pharmacology), employing two NP databases, InflamNat and BIOFACQUIM, three senoylitic compounds were identified [152]. Table 4 summarizes the main applications of representative Latin American natural product databases to identify bioactive compounds.…”