Work

Toxicity Profiling and In Vivo Metabolism of Danshensu-Derived Novel Antihypertensive Candidate 221s (2,9)

Year: 2025

Type: article

Abstract: Compound 221s (2,9) is a novel antihypertensive drug candidate synthesized utilizing danshensu, borneol, and proline by using the strategy of combinatorial molecular chemistry. This study aimed to systematically identify the safety of danshensu-derived compound 221s (2,9) by conducting an acute toxicity test and long-term toxicity study and to elucidate the in vivo metabolic pathways of 221s (2,9) in order to provide critical insights into the observed toxicity. In the acute toxicity study, a single oral dose of 221s (2,9) at 3000 mg/kg in mice produced no clinical signs of toxicity or mortality, indicating an MTD of 3000 mg/kg. In a subsequent 12-week repeated-dose toxicity study in rats, doses of 20, 40, and 80 mg/kg were well tolerated, with no adverse clinical observations or deaths. Notably, organ coefficient analysis revealed transient lung injury, which resolved following a 4-week recovery period. The metabolite identification study indicated that metabolism in rats is predominated by Phase II metabolites, potentially contributing to the low toxicity of 221s (2,9). Further investigation into the impact of the drug metabolic enzyme-transporter interplay on the in vivo disposition of 221s (2,9) is warranted.

Source: Toxins

DOI: 10.3390/toxins17090436

Authors: Yunmei Chen, Kuan Yang, Lili Yu, Rong Wang, Shaojing Liu, Bei Qin

Institution: Xi'an Medical University

Language: English

Topic: Traditional Chinese Medicine Analysis

Subfield: Complementary and alternative medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258