11-Azaartemisinin derivatives bearing halogenated aromatic moieties: Potent anticancer agents with high tumor selectivity.

Autor: Nguyen DT; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam. Electronic address: vnnguyentiendung@gmail.com., Ngo TH; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Tran MT; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Nguyen HTT; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Ho HT; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Nguyen DV; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Nguyen TT; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Ly KD; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Nguyen TT; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Vuong TT; Vietnam University of Traditional Medicine, No. 2 Tran Phu St., Ha Dong, Hanoi 12110, Viet Nam., Tran HV; NTT Hi-Tech Institute, Nguyen Tat Thanh University, 298-300A Nguyen Tat Thanh Street, District 4, Ho Chi Minh City 7280, Viet Nam. Electronic address: tranhung@ntt.edu.vn.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Nov 15; Vol. 113, pp. 129969. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1016/j.bmcl.2024.129969
Abstrakt: While artemisinin and its derivatives, including 11-azaartemisinin-based compounds, have shown promising anticancer activity, the integration of halogens into aromatic structures can amplify drug potency, metabolic stability, and selectivity. Herein, we present the synthesis of new novel 11-azaartemisinin derivatives bearing halogenated aromatic moieties connected via 1,2,3-triazole bridges and evaluate their anticancer activities against three human tumor cell lines: epidermoid carcinoma (KB), hepatocellular carcinoma (HepG2), and human lung adenocarcinoma (A549). Among the synthesized compounds, six of them (8c-h) displayed good to excellent antiproliferative activity in the low micromolar range across all three human cancer cell lines. In general, the m-bromide (8c) and m-iodide (8d) compounds exhibited superior anticancer activities compared to their o- and p-analogs, as well as the m-chloride and m-fluoride compounds. The most promising m-Br compound (8c) displayed 50 % inhibition of KB, HepG2, and A549 cell growth at concentrations of 7.7, 42.5, and 15.5 μM, respectively. Notably, the m-Br compound (8c) exhibited approximately 32-, 6-, and 16-fold lower activity in normal cells (Hek293) compared to KB, HepG2, and A549 tumor cells, respectively, indicating a significant tumor-selectivity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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