Antimicrobial Phenolic Constituents of Dalea candida var. oligophylla, Including New 3-Hydroxyflavanones, a New Flavanone, and a New Pawhuskin

A phytochemical investigation of Dalea candida var. oligophylla was undertaken. Column chromatographic efforts were followed by structure determination using extensive NMR spectroscopy and supported by CD spectroscopy, optical rotary dispersion, and HRESIMS. These studies initially revealed pawhuskin D (1), a new geranylated stilbene. Further work revealed two new 3-hydroxyflavanones (2 and 4) and a new flavanone (3). Compounds 2–4 are prenylated or contain a cyclized geranyl group and were summarily named candidans A–C. A suite of known phenolic compounds (5–10) was also isolated, and all compounds were evaluated for in vitro activity against the pathogens methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus faecalis (VRE), Cryptococcus neoformans, and Candida albicans. Candidan C (3) was the most active of the new compounds, with MICs to MRSA and C. neoformans of 8.4 and 7.6 μM, respectively. C. neoformans was particularly susceptible to (-)-rotenone (10) with an MIC value of 1.1 μM. Pawhuskin D was also evaluated for broad opioid receptor affinity in a competitive binding assay with [3H]-naloxone but was found to be less active than pawhuskins A–C that were earlier proven to be in vitro κ-opioid antagonists.