Metabolites Isolated from Senecio nutans Sch. Bip and Their Synthesized Oximes Inhibit Angiotensin I-Converting Enzyme Activity in Vascular Smooth Muscle

Figures

• 

  Figure 1. Metabolites isolated from Senecio nutans Sch. Beep. 5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofuran (1) and 4-hydroxy-3-(3-methyl-2-butenyl) acetophenone (3) and their respective oximes (2 and 4).

• 

  Figure 2. Graph showing the percentage of inhibition of ACE activity. Activity was determined in the presence of S. nutans extract (A) and different compounds in increasing concentrations (10−8 to 10−5 M) compared to the positive control captopril (10−8 to 10−5 M; (B)). (C) compares 3 and its oxime, while (D) is compared to 1 and its oxime. Values represent the mean ± relative standard error (3–4 experiments).

• 

  Figure 3. Effect of S. nutans and pure compounds on the vascular contractile response to Angiotensin I. The aortic rings were preincubated with the vehicle for 20 min (Control; (A)), S. nutans extract (Sn; 100 µg/mL; (B)), captopril (10−5 M; (C)), 1 (10−5 M; (D)), 2 (10−5 M; (E)), 3 (10−5 M; (F)), 4 (10−5 M; (G)), and then angiotensin I (Ang I; 10−6 M) was added to the bath. Previously, aortic rings precontracted with PE (10−6 M) and relaxed with ACh (10−5 M) were added to the bath to evaluate the vascular endothelium. The X axis means time (min) and the Y axis represents the force of contraction (g).

• 

  Figure 4. S. nutans and their pure compounds reduced the contractile response to angiotensin I (Ang I; 10−6 M). The aortic rings were pre-incubated for 20 min with S. nutans extract (Sn; 100 µg/mL) and different compounds (10−5 M) compared to the positive control captopril (Capto; 10−5 M). Values represent the mean ± relative standard error in duplicate of 4–5 experiments. * p < 0.05, ** p < 0.01 vs. Control. ns: not significant.

• 

  Figure 5. Graph of the affinity energies of the compounds studied the different Angiotensin-Converting Enzyme (ACE) receptor proteins. All values on the bar are expressed in energy units (kcal/mol).

• 

  Figure 6. Interactions between the studied ligands with ACE in the binding site. The purple sphere represents the zinc atom, while compounds (A) 2, (B) 1, (C) 4, and (D) 3 are shown in their respective poses obtained by molecular docking in the 7Q24 crystal as a representation of crystallized proteins.