Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 5; p. 1380
• Main Authors: Wu, Xiutao, Gong, Lijie, Chen, Chen, Tao, Ye, Zhou, Wuxi, Kong, Lingyi, Luo, Jianguang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.03.2021; MDPI
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; antiproliferative activity; Cancer; Cell Proliferation; Cytotoxicity; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Harringtonines - chemistry; harringtonolide; Humans; Molecular Structure; Natural products; Neoplasms - drug therapy; Structure-Activity Relationship; structure-activity relationship (SAR); troponoids; structure-activity relationship (SAR); harringtonolide; antiproliferative activity; troponoids
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26051380

Harringtonolide (HO), a natural product isolated from Cephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound 6 exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.