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Updated: Apr 16, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis of isocryptolepine analogues and their structure-activity relationship studies as antiplasmodial and
Pasuk Aroonkit1, Charnsak Thongsornkleeb2, Jumreang Tummatorn2
1Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand.
Abstract:
Novel isocryptolepine analogues have been conveniently synthesized and evaluated for antimalarial and antiproliferative activities. We have found 3-fluoro-8-bromo-isocryptolepine (1n) to have the highest activities against chloroquine-resistant K1, chloroquine-sensitive 3D7, and chloroquine- and mefloquine-resistant SKF58 and SRIV35 strains. Several fluorine-substituted analogues (1b, 1n, and 1q) also showed excellent selectivities while maintaining good to excellent activities against all four Plasmodium falciparum strains. Additionally, antiproliferative properties of isocryptolepine derivatives against HepG2, HuCCA-1, MOLT-3 and A549 cancer cell lines are reported for the first time in this study. 2-Chloroisocryptolepine (1c) and benzo-fused-2-chloroisocryptolepine (1i) showed significant bioactivities whereas several novel fluorinated compounds and 2-chloro-8-bromoisocryptolepine (1f) displayed excellent selectivities.
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