Synthesis and evaluation of 9,9-dimethylxanthene tricyclics against trypanothione reductase, Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani

TY - JOUR

T1 - Synthesis and evaluation of 9,9-dimethylxanthene tricyclics against trypanothione reductase, Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani

AU - Chibale, Kelly

AU - Visser, Mark

AU - Yardley, Vanessa

AU - Croft, Simon L.

AU - Fairlamb, Alan H.

N1 - Funding Information: We thank Ahilan Saravanamuthu and Dr. David Parkin for help with enzyme assays, Peter J. Rock and Diane Rowland for help with the antiparasitic in vitro assays. Financial support from the Wellcome Trust (International Research Development grant to KC, grant no. 052075/Z/97). Additional support from the University of Cape Town and Foundation for Research Development (KC) is gratefully acknowledged. This investigation received financial support from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) (SLC and VY). AHF is supported by the Wellcome Trust.

PY - 2000/6/5

Y1 - 2000/6/5

N2 - Derivatives of 9,9-dimethylxanthene was synthesised and evaluated against trypanothione reductase (TR) and in vitro against parasitic trypanosomes and leishmania. High in vitro antiparasitic activity was observed for some derivatives with one compound showing high activity against all three parasites (ED50 values of 0.02, 0.48 and 0.32 μM, for Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani, respectively). The lack of correlation between inhibitory activity against TR and ED50 values suggests that TR is not the target. (C) 2000 Elsevier Science Ltd. All rights reserved.

AB - Derivatives of 9,9-dimethylxanthene was synthesised and evaluated against trypanothione reductase (TR) and in vitro against parasitic trypanosomes and leishmania. High in vitro antiparasitic activity was observed for some derivatives with one compound showing high activity against all three parasites (ED50 values of 0.02, 0.48 and 0.32 μM, for Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani, respectively). The lack of correlation between inhibitory activity against TR and ED50 values suggests that TR is not the target. (C) 2000 Elsevier Science Ltd. All rights reserved.

UR - https://www.scopus.com/pages/publications/0034608699

U2 - 10.1016/S0960-894X(00)00154-2

DO - 10.1016/S0960-894X(00)00154-2

M3 - Article

C2 - 10866368

AN - SCOPUS:0034608699

SN - 0960-894X

VL - 10

SP - 1147

EP - 1150

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

ER -