Extended Data Fig. 9: Toxicity, chemical properties, and in vivo efficacy of compounds 1 and 2. | Nature

Extended Data Fig. 9: Toxicity, chemical properties, and in vivo efficacy of compounds 1 and 2.

From: Discovery of a structural class of antibiotics with explainable deep learning

Extended Data Fig. 9

a, Fractional hemolysis measurements of human red blood cells (RBCs) treated with compounds 1 and 2 at the indicated final concentrations. Vehicle (1% DMSO) was used as a negative control, and Triton X-100, a detergent, was used as a positive control. Black points indicate values from two biological replicates, and red bars indicate average values. b, Ferrous iron chelation measurements of compounds 1 and 2. Vehicle (1% DMSO) was used as a negative control, and ethylenediaminetetraacetic acid (EDTA), an iron chelator, was used as a positive control. Black points indicate values from two biological replicates, and gray bars indicate average values. c, Ames test mutagenesis measurements of the fractions of revertant S. typhimurium TA100 cultures treated with compounds 1 and 2 at the indicated final concentrations. Vehicle (1% DMSO) was used as a negative control, and 5 µg/mL sodium azide was used as a positive control. Black points indicate values from two biological replicates, and purple bars indicate average values. Higher fractions of revertant cultures indicate higher mutagenic potential (inset). d, Chemical stability of compound 1 in various buffers as a function of incubation time at 37 °C. Values are normalized to the mean measurement at time zero, and each point is representative of the mean of two biological replicates. Error bars indicate the full range of values arising from two biological replicates. e, Photographs of WoundSkin models 24 h after topical treatment with compound 1 (1%) or DMSO vehicle. Images are representative of six biological replicates in each treatment group. Scale bar, 2 mm. f, Illustration of the in vivo study of a neutropenic mouse wound infection model using MRSA CDC 563 shown in Fig. 5a of the main text. g, Illustration of the in vivo study of a neutropenic mouse thigh infection model using MRSA CDC 706 shown in Fig. 5b of the main text.

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