Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2,3-b]thiophen-4,9-quinones

TY - JOUR

T1 - Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2,3-b]thiophen-4,9-quinones

AU - Zani, Carlos L.

AU - Chiari, Egler

AU - Krettli, Antoniana U.

AU - Murta, Silvane M.F.

AU - Cunningham, Mark L.

AU - Fairlamb, Alan H.

AU - Romanha, Alvaro J.

N1 - Funding Information: We are gratefutl o NCI-FCRDC for runningt he mass spectrao f the quinonesT. his work was supportedin Brazil by grantsf rom PAPES-FIOCRUZ, PRONEX. AHF was supportedb y a grant from the Wellcome Trust. We are also thankful to the CNPq fellows H. Marinuzzia nd L. S. R. Soaresf or runnings omeo f the in vitro bioassayws ith P. falciparum

PY - 1997/12

Y1 - 1997/12

N2 - Naphtho[2,3-b]thiophen-4,9-quinone and five derivatives were prepared using the Friedel-Crafts reaction and tandem-lithiation of aromatic diethylamides. These quinones were evaluated for their trypanocidal and anti-plasmodial activities by their effects on: (1) growth of epimastigote 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. falciparum at 0.2 μM. 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 exhibited weak activity at 4°C against trypomastigotes in murine blood as well against the enzyme trypanothione reductase. Further structural modifications will be necessary to improve the in vivo activity of the naphthothiophenquinones.

AB - Naphtho[2,3-b]thiophen-4,9-quinone and five derivatives were prepared using the Friedel-Crafts reaction and tandem-lithiation of aromatic diethylamides. These quinones were evaluated for their trypanocidal and anti-plasmodial activities by their effects on: (1) growth of epimastigote 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. falciparum at 0.2 μM. 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 exhibited weak activity at 4°C against trypomastigotes in murine blood as well against the enzyme trypanothione reductase. Further structural modifications will be necessary to improve the in vivo activity of the naphthothiophenquinones.

KW - Naphthothiophenquinones

KW - Plasmodium berghei

KW - Plasmodium falciparum

KW - Trypanosoma cruzi

KW - Trypanothione reductase

UR - https://www.scopus.com/pages/publications/0031438570

U2 - 10.1016/S0968-0896(97)00155-7

DO - 10.1016/S0968-0896(97)00155-7

M3 - Article

C2 - 9459016

AN - SCOPUS:0031438570

SN - 0968-0896

VL - 5

SP - 2185

EP - 2192

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 12

ER -