PMC

Structures of first generation analogs 10 – 20

Chemical structures of isolated natural products 1 and 2 and similar diaryloxazoles reported from other plant species.

Compound 17 more potently inhibits growth of MDA-MB-453 cells than natural product hits. SRB assay concentration-response curves for 17 (A) and potency measurements (B) in five TNBC cell lines representing different molecular subtypes. Results represent mean ± SE.

Compound 30 rapidly decreases abundance of activated mTORC1 signaling proteins in LAR cells. Immunoblotting of compound 30-treated MDA-MB-453 whole-cell lysates for phosphorylated and total PI3K/Akt/mTORC1 signaling proteins. Cells were treated with vehicle (DMSO) or 1 μM 30 for 1 – 6 h, as indicated. Quantification of phosphorylated protein relative to total protein is indicated below each band.

Amyris texana, extract and isolated compounds selectively inhibit growth of LAR cells. SRB assay concentration-response curves for a crude supercritical CO₂ extract of Amyris texana (A); fractions F2 (B) and F3 (C); and isolated pure compounds 1 (D) and 2 (E) against TNBC cell lines representing different molecular subtypes.

Second generation analogs selectively inhibit growth of LAR cell lines MDA-MB-453 and SUM-185PE. SRB assay concentration-response curves for 24 (A), 26 (B), 27 (C), 28 (D), 30 (E) and 31 (F) in six TNBC cell lines representing five different molecular subtypes. Results represent mean ± SE.

Reagent and conditions: (a) NaH (1.1 equiv.), prenylbromide (1 equiv.), ACN (1.0M), 0 °C, 61% yield; (b) p-Toluenesulfonylmethylisocyanide (1.0 equiv.), K₂CO₃ (1.7 equiv.), MeOH (0.2M), reflux, 98%; (c) 2-bromonicotinaldehyde or 3- bromonicotinaldehyde, Cui (1 equiv.), PPh₃ (1 equiv.), Na₂CO₃ (2 equiv.), DMF (1.0M), 160 °C, 47% yield; (d) HNR, R₂ (1.1 equiv.), NaHB(OAc)₃, DCE, r.t., 21-71% yield; (e) HC1 (1.0 equiv.), ether (1.0M), r.t.

Reagent and conditions: (a) p- Toluenesulfonylmethylisocyanide (1.0 equiv.), K₂CO₃ (1.7 equiv.), MeOH (0.2M), reflux, 97%; (b) Pd(OAc)₂ (0.2 equiv.), Cui (1 equiv.), K₂C0₃ (2 equiv.), Ar-Br (1.2 equiv.), DMF (0.85M), mW, 150 °C, 41-55%; (c) Ar-Br (1.2 equiv.), Cui (1 equiv., PPh₃ (1 equiv.), Na₂CO₃ (2 equiv.), DMF (1.0M), 30-65% yield; (d) BBr₃ (6 equiv.), DCM (0.2M), −78 °C to r.t., 96% yield; (e) NaH (1.1 equiv.), R-Br (1.1 equiv.), THF/DMF (0.1M), 0 °C to r.t, 28-63%; (f) benzoic acid, HATU, DIPEA, DMF, 57% yield; (g) Cone. H₂SO₄, AC₂O, 90 °C, 85% yield.