Drug repurposing: Discovery of troxipide analogs as potent antitumor agents

Abstract

Drug repurposing plays a vital role in the discovery of undescribed bioactivities in clinical drugs. Based on drug repurposing strategy, we for the first time reported a novel series of troxipide analogs and then evaluated their antiproliferative activity against MCF-7, PC3, MGC-803, and PC9 cancer cell lines and WPMY-1, most of which showed obvious selectivity toward PC-3 over the other three cancer cell lines and WPMY-1. Compound 5q, especially, could effectively inhibit PC3 with an IC 50 value of 0.91 mM, which exhibited around 53-fold selectivity toward WPMY-1. Data indicated that 5q effectively inhibited the colony formation, suppressed the cell migration, and induced G1/S phase arrest in PC3 cells. Also, compound 5q induced cell apoptosis by activating the two apoptotic signaling pathways in PC3 cells: death receptor-mediated extrinsic pathway and mitochondria-mediated intrinsic pathway. Compound 5q up-regulated the expression of both pro-apoptotic Bax and P53, while down-regulated anti-apoptotic Bcl-2 expression. Besides, compound 5q significantly increased the expression of cleaved caspase 3/9 and cleaved PARP. Therefore, the successful discovery of compound 5q may further validate the feasibility of this theory, which will encourage researchers to reveal undescribed bioactivities in traditional drugs.

Paradigm Shift: A Comprehensive Review of Ovarian Cancer Management in an Era of Advancements

“…This strategy cuts research costs and speeds up drug usage as the repurposed drugs have already been deemed safe in preclinical models and humans. As a result, drug repurposing has achieved great success, leading to the identification of candidate drugs for a pleura of diseases [208].…”

Mesoporous Bioactive Glasses in Cancer Diagnosis and Therapy: Stimuli‐Responsive, Toxicity, Immunogenicity, and Clinical Translation

“…Developing antitumor therapeutics have typically encountered several restrictions in terms of clinical impacts, especially for their side effects against healthy tissues. [258] Although numerous in vitro studies have indicated that MBGs combined with chemotherapy agents and ions could suppress tumor cells' activity with limited toxicity against normal cells, there are limited precise in vivo studies and almost nonexistent clinical research in this field. In light of this, a significant issue that should be carefully investigated in the future is the risk of toxicity in a broad context, including systemic, tissues, and organs affected by MBGs.…”

Livro de Resumos do V Encontro Regional da Sociedade Brasileira de Química SBQ Centro Oeste

“…A troxipida apresenta atividade anti-inflamatória e é utilizada no tratamento de refluxo 5 . Através de modificações químicas, Lu et al (2020) demonstraram a eficácia dos análogos de troxipida no combate de células de câncer de próstata, assim como de outros cânceres. Os pesquisadores determinaram a concentração inibitória média (IC50) de 22 derivados análogos à troxipida onde 11 demonstraram atividade contra as células do câncer de próstata.…”