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Updated: May 31, 2026

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples
Published on: December 2, 2022
Unprecedented citrinin trimer tricitinol B functions as a novel topoisomerase IIα inhibitor
Lin Du1, Hong-Chun Liu, Wei Fu
1Key laboratory of Marine Drugs, the Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, PR China.
Abstract:
Fifteen citrinin derivatives (1-4, 6-16), including two unprecedented citrinin trimers tricitrinols A (3) and B (4), were isolated from Penicillium citrinum HGY1-5. The six-membered ring A system is essential for the cytotoxicity of active dimers (1, 2, and 5) and trimers (3 and 4). Tricitrinol B (4) showed extensive cytotoxicity in 17 tumor cells with comparable low-micromolar IC(50) values (1-10 μM) and potential antimultidrug resistance capabilities. Tricitrinol B (4) induced cell apoptosis in HL60 and HCT116 cells via mainly extrinsic pathways and G2/M arrest. Further antitumor mechanism study and computational docking analysis indicated that tricitrinol B (4) works as an intercalating topoisomerase IIα (topo IIα) poison, which inhibits the enzyme activity of topo IIα by interfering predominantly with the topo IIα-mediated poststrand-passage cleavage/religation equilibrium over with the prestrand-passage one and induced DNA damage. Tricitrinol B (4) represents a novel class of topo IIα-inhibitory skeletons for developing new chemotherapeutic agents.
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