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Antimalarial activity of tetrahydro-β-carbolines targeting the ATP binding pocket of the Plasmodium falciparum heat shock 90 protein.

Abstract：

:A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitude greater than the original lead compound was found. Additional modeling of this new lead compound suggests multiple avenues to further increase potency against this target, potentially paving the path for a therapeutic with a mode of action different than any current clinical treatment.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Eagon S,Hammill JT,Bach J,Everson N,Sisley TA,Walls MJ,Durham S,Pillai DR,Falade MO,Rice AL,Kimball JJ,Lazaro H,DiBernardo C,Kiplin Guy R

doi

10.1016/j.bmcl.2020.127502

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

127502

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30613-2

journal_volume

30

pub_type

杂志文章

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