Structure and Activity of the Camellia oleifera Sapogenin Derivatives on Growth and Biofilm Inhibition of Staphylococcus aureus and Escherichia coli

Sapogenin is the main block of Camellia oleifera saponin, which was purified and structurally modified by the C28 acylation reaction to synthesize 19 new derivatives. The growth and biofilm inhibition of Staphylococcus aureus and Escherichia coli was measured to evaluate their antibacterial effects. A three-dimensional quantitative structure–activity relationship (3D-QSAR) assay indicated that the antibacterial activities were significantly enhanced after sapogenin was modified with an aromatic ring or heterocyclic ring and electron-withdrawing substituents at the meta or para position. Among them, the derivative of sapogenin with a 2-mercapto-4-methyl-5-thiazolyl acetyl group obviously destroyed bacterial biofilm and made bacteria lysis. 3D-QSAR provides practical information for the structural design of sapogenin derivatives with strong antibacterial activity, and the C. oleifera sapogenin derivative 28-O-(2-mercapto-4-methyl-5-thiazolyl)-3β,16α,21β,22α-O-tetrahydroxy-oleantel-2-ene-23-aldehyde (S-16) is an effective candidate as an antibacterial agent for the prevention of bacterial resistance against antibiotics.