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. Author manuscript; available in PMC: 2022 Apr 19.
Published in final edited form as: Angew Chem Int Ed Engl. 2021 Mar 11;60(17):9279–9283. doi: 10.1002/anie.202015845

Figure 4.

Figure 4.

TDI-8304 inhibits growth of erythrocytic stage P. falciparum. A) TDI-8304 potently inhibited Pf3D7 growth (open black circles) but is not cytotoxic for HepG2 human hepatoma cells (solid black circles); B) TDI-8304 inhibits growth of Pf Dd2 and two proteasome inhibitor-resistant strains, Pf Dd2β6A117D and Pf Dd2β5A49S. C) TDI-8304 at 1 μM led to accumulation of polyubiquitinated proteins after treatment of P. falciparum schizonts for 6 hours. D) EC50 values of TDI-8304 against P. falciparum strains with various drug resistance profiles; E) Ex vivo activity of TDI-8304 against 38 clinical isolates from Uganda in years 2018 and 2019. The geometric mean EC50 was 18 nM. Each black spot represents a single P. falciparum isolate. Blue and green spots represent Dd2 and 3D7 laboratory controls, respectively. F) In vitro synergy of TDI-8304 and DHA against artemisinin-sensitive P. falciparum Dd2 Cam3.IRev and artemisinin-resistant Cam3.IR539T. Data were average of two independent experiments and each in duplicates. FIC: fractional inhibitory concentration.