Two New Aristolochic Acid Analogues from the Roots of <i>Aristolochia</i> <i>contorta</i> with Significant Cytotoxic Activity

• Main Authors: Hong-Jian Ji, Jia-Yuan Li, Shi-Fei Wu, Wen-Yong Wu, Chang-Liang Yao, Shuai Yao, Jian-Qing Zhang, De-An Guo
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: Molecules
• Subjects: Aristolochia contorta; aristolochic acid; cytotoxicity; molecular docking
• Online Access: https://www.mdpi.com/1420-3049/26/1/44

Twelve compounds, including two new aristolochic acid analogues with a formyloxy moiety (9–10) and 10 known aristolochic acid derivates (1–8 and 11–12), were obtained from the roots of <i>Aristolochia</i> <i>contorta</i>. Their structures were elucidated using extensive spectroscopic methods. Their cytotoxic activity in human proximal tubular cells HK-2 was evaluated by the MTT method, which has been widely used to assess cell viability. Among these molecules, compounds <b>3 </b>and <b>9 </b>were found to be more cytotoxic. Furthermore, molecular modeling was used to evaluate, for the first time, the interactions of compounds <b>3</b> and <b>9</b> with the target protein organic anionic transporter 1 (OAT1) that plays a key role in mediating aristolochic acid nephropathy. Structure–activity relationships are briefly discussed.