ANTI-PLASMODIAL AND ANTITRYPANOSOMAL ACTIVITY OF SYNTHETIC NAPHTHO[2,3-B]THIOPHEN-4,9-QUINONES

Naphtho[2,3-b]thiophen-4,9-quinone and five derivatives were prepared using the Friedel-Crafts reaction and tandem-lithiation of aromatic di ethylamides. These quinones were evaluated for their trypanocidal and anti-plasmodial activities by their effects on: (1) growth of epimasti gote forms of Trypanosoma cruzi in vitro, (2) lysis of trypomastigote forms of T. cruzi in murine blood, (3) growth of Plasmodium falciparum in vitro, and (4) inhibition of the recombinant enzyme trypanothione reductase. The parent compound, naphtho[2,3-b]thiophen-4,9-quinone (3a ), was among the most active quinone tested in vitro against P. falcip arum at 0.2 mu M. However, it was inactive against P. berghei-infected mice treated with 2.3 mmol/kg daily for 5 days. Most of the quinones prepared were active against T. cruzi epimastigotes in culture but exh ibited weak activity at 4 degrees C against trypomastigotes in murine blood as well against the enzyme trypanothione reductase. Further stru ctural modifications will be necessary to improve the in vivo activity of the naphthothiophenquinones. (C) 1997 Elsevier Science Ltd.