Protein Synthesis Inhibitors

Publication Title: 
Memórias Do Instituto Oswaldo Cruz

A cell-free system from Plasmodium falciparum able to translate endogenous mRNA was used to determine the effect of artemisinin, chloroquine and primaquine on the protein synthesis mechanism of the parasite. The antimalarial drugs did not inhibit the incorporation of [3H] methionine into parasite proteins even at concentrations higher than the ones found to strongly inhibit the parasite growth. Results clearly indicate that these compounds do not have a direct effect on protein synthesis activity of P. falciparum coded by endogenous mRNA.

Ferreras, Ana
Triana, Ledia
Sánchez, Erlinda
Herrera, Flor
Publication Title: 
Science (New York, N.Y.)

Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-beta-carbolines, or spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4).

Rottmann, Matthias
McNamara, Case
Yeung, Bryan K. S.
Lee, Marcus C. S.
Zou, Bin
Russell, Bruce
Seitz, Patrick
Plouffe, David M.
Dharia, Neekesh V.
Tan, Jocelyn
Cohen, Steven B.
Spencer, Kathryn R.
González-Páez, Gonzalo E.
Lakshminarayana, Suresh B.
Goh, Anne
Suwanarusk, Rossarin
Jegla, Timothy
Schmitt, Esther K.
Beck, Hans-Peter
Brun, Reto
Nosten, François
Renia, Laurent
Dartois, Veronique
Keller, Thomas H.
Fidock, David A.
Winzeler, Elizabeth A.
Diagana, Thierry T.
Publication Title: 
Journal of Basic and Clinical Physiology and Pharmacology

We investigated the protective effect of Withania somnifera root powder (used in ayurvedic medicine in India) on gentamicin (GEN) induced nephrotoxicity in male Wistar rats. The root powder was administered orally to rats for 14 days before GEN treatment and thereafter with GEN for 8 days.

Jeyanthi, Thangavel
Subramanian, Perumal
Publication Title: 
Nature Neuroscience

A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing treatment with morphine resulted in downregulation of the K(+)-Cl(-) co-transporter KCC2, impairing Cl(-) homeostasis in rat spinal lamina l neurons. Restoring the anion equilibrium potential reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia.

Ferrini, Francesco
Trang, Tuan
Mattioli, Theresa-Alexandra M.
Laffray, Sophie
Del'Guidice, Thomas
Lorenzo, Louis-Etienne
Castonguay, Annie
Doyon, Nicolas
Zhang, Wenbo
Godin, Antoine G.
Mohr, Daniela
Beggs, Simon
Vandal, Karen
Beaulieu, Jean-Martin
Cahill, Catherine M.
Salter, Michael W.
De Koninck, Yves
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