Figure 6.
Appending a sterically-unencumbered amine on relatively flat and rigid antibiotics can enhance their activity against Gram-negative bacteria. (A) Seven examples75, 128, 132-136, 151 of conversions of Gram-positive-only compounds into broad-spectrum antibiotics via addition of a primary amine, all are consistent with the eNTRy rules. (B) Two examples of conversions to broad-spectrum antibiotics that are not consistent with the eNTRy rules, both converted compounds are diamines and may enter Gram-negative bacteria through the self-promoted uptake pathway. RB = rotatable bonds; Glob = globularity; Broad-spectrum = activity against both Gram-positive and Gram-negative bacteria; PA = P. aeruginosa; MIC = minimum inhibitory concentration.