Structural analysis of chloroquine resistance reversal by imipramine analogs.
نویسندگان
چکیده
For imipramine, desipramine, and eight analogs of these well-known drugs, an N-5-aminoalkyl substitution was a minimum but insufficient structural feature associated with chloroquine resistance reversal. Although a second distal aliphatic nitrogen atom was unnecessary for resistance reversal, the direction of the dipole moment vector was critical.
منابع مشابه
Contrasting ex vivo efficacies of "reversed chloroquine" compounds in chloroquine-resistant Plasmodium falciparum and P. vivax isolates.
Chloroquine (CQ) has been the mainstay of malaria treatment for more than 60 years. However, the emergence and spread of CQ resistance now restrict its use to only a few areas where malaria is endemic. The aim of the present study was to investigate whether a novel combination of a CQ-like moiety and an imipramine-like pharmacophore can reverse CQ resistance ex vivo. Between March to October 20...
متن کاملReversal of Plasmodium falciparum resistance to chloroquine in Panamanian Aotus monkeys.
An Aotus-Plasmodium falciparum model was used to determine if chloroquine resistance could be reversed in vivo. The putative resistance modulators tested all reverse chloroquine resistance in vitro and included verapamil, chlorpromazine, prochlorperazine, cyproheptadine, ketotifen, a tiapamil analog (Ro 11-2933), and a chlorpromazine analog (SKF 2133-A). Combinations of chloroquine plus chlorpr...
متن کاملA comprehensive in silico analysis of pathogenic nsSNPs in the NT5C2 gene involved in relapsed ALL
Background: About 10-20% of children suffering from acute lymphoblastic leukemia (ALL), experience a relapse, which is a major cause of their death. Purine nucleotide analogs are frequently prescribed to maintain the treatment of ALL. Cytosolic 5´-nucleotidase (NT5C2) catalyzes the 5´ dephosphorylation of purine analogs. Gain-of-function mutations in the NT5C2 gene result in resistance to the t...
متن کاملReversal of chloroquine resistance in Plasmodium falciparum using combinations of chemosensitizers.
Research into chloroquine resistance reversal in Plasmodium falciparum has revealed a widespread range of functionally and structurally diverse chemosensitizers. However, nearly all of these chemosensitizers reverse resistance optimally only at concentrations that are toxic to humans. Verapamil, desipramine, and trifluoperazine were shown to potentiate chloroquine accumulation in a chloroquine-...
متن کاملIn vitro antimalarial activity of a new organometallic analog, ferrocene-chloroquine.
The in vitro activities of new organometallic chloroquine analogs, based on 4-amino-quinoleine compounds bound to a molecule of ferrocene, were evaluated against chloroquine-susceptible, chloroquine-intermediate, and chloroquine-resistant, culture-adapted Plasmodium falciparum lineages by a proliferation test. One of the ferrocene analogs totally restored the activity of chloroquine against chl...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 45 9 شماره
صفحات -
تاریخ انتشار 2001