Antiparasitic lethality of sulfonamidebenzamides in kinetoplastids.
Basic Information
ID: ALA3994630
Journal: Bioorg Med Chem Lett
Title: Antiparasitic lethality of sulfonamidebenzamides in kinetoplastids.
Authors: Hackler A, Patrick SL, Kahney EW, Flaherty DP, Sharlow ER, Morris JC, Golden JE.
Abstract: A sulfonamidebenzamide series was assessed for anti-kinetoplastid parasite activity based on structural similarity to the antiparasitic drug, nifurtimox. Through structure-activity optimization, derivatives with limited mammalian cell toxicity and increased potency toward African trypanosomes and Leishmania promastigotes were developed. Compound 22 had the best potency against the trypanosome (EC50=0.010μM) while several compounds showed ∼10-fold less potency against Leishmania promastigotes without impacting mammalian cells (EC50>25μM). While the chemotype originated from an unrelated optimization program aimed at selectively activating an apoptotic pathway in mammalian cancer cells, our preliminary results suggest that a distinct mechanism of action from that observed in mammalian cells is responsible for the promising activity observed in parasites.
CiteXplore: 28119024
DOI: 10.1016/j.bmcl.2017.01.043
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