2. Academic Validation
  3. Synthesis of isocryptolepine analogues and their structure-activity relationship studies as antiplasmodial and antiproliferative agents

Synthesis of isocryptolepine analogues and their structure-activity relationship studies as antiplasmodial and antiproliferative agents

  • Eur J Med Chem. 2015 Apr 13:94:56-62. doi: 10.1016/j.ejmech.2015.02.047.
Pasuk Aroonkit 1,  Charnsak Thongsornkleeb 2,  Jumreang Tummatorn 3,  Suppachai Krajangsri 4,  Mathirut Mungthin 5,  Somsak Ruchirawat 6
Affiliations

Affiliations

  • 1 Program 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.
  • 2 Program 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; Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand. Electronic address: charnsak@cri.or.th.
  • 3 Program 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; Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand. Electronic address: jumreang@cri.or.th.
  • 4 Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand.
  • 5 Department of Parasitology, Phramongkutklao College of Medicine, Ratchawithi Road, Bangkok 10400, Thailand.
  • 6 Program 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; Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand.
PMID: 25747499 DOI: 10.1016/j.ejmech.2015.02.047
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.

Keywords

Antiplasmodial; Antiproliferative; Azide rearrangement; Cytotoxicity; Indoloquinoline alkaloid; Isocryptolepine.

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