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

**Brett D. Schwartz 1, Mark J. Coster 1, Tina S. Skinner-Adams 1, Katherine T. Andrews 1, Jonathan M. White <sup>2</sup> and Rohan A. Davis 1,\***


Academic Editor: Sylvia Urban

Received: 14 August 2015; Accepted: 7 September 2015; Published: 15 September 2015

**Abstract:** Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1*H*-indole-4,7-dione and 1-tosyl-1*H*-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.

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