Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D

Marine Drugs

Brett D. Schwartz¹  Mark J. Coster¹  Tina S. Skinner-Adams¹  Katherine T. Andrews¹  Jonathan M. White²  Rohan A. Davis¹ 

[1] Eskitis Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, Australia; E-Mails:;School of Chemistry and Bio21 Institute, University of Melbourne, Parkville, Vic 3052, Australia; E-Mail:

关键词: synthesis;    thiaplakortone;    regioisomer;    tricyclic;    natural product scaffold;    X-ray;    crystal;    Plasmodium falciparum;    antiplasmodial;    cytotoxicity;   

DOI  :  10.3390/md13095784

来源: mdpi

【 摘 要 】

Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in the thiaplakortones. All compounds were fully characterized using NMR and MS data. A single crystal X-ray structure was obtained on one of the N-tosyl derivatives. All compounds were screened for in vitro antiplasmodial activity against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC₅₀ < 500 nM) but only moderate selectivity for P. falciparum versus human neonatal foreskin fibroblast cells.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.