Towards cytotoxic and selective derivatives of maslinic acid

New inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 7-hydroxycoumarin and monoterpenoid moieties

“…13 C-NMR (CDCl 3 , δ C ): 153.32 (s, C(1)); 162.00 (s, C(2)); 120.64 (s, C(3)); 147.12 (s, C(4));113.95 (s, C(5)); 124.05 (d, C(6)); 112.50 (d, C(7)); 160.27 (s, C(8)); 101.54 (d, C(9)); 23.72 (t, C(10)); 21.55 (t, C(11)); 21.26 (t, C(12)); 25.11 (t, C(13)); 70.53 (t, C (14) 17)); 6.75 (d, 1H, J(9,7)=2.5, H-C(9)); 6.79 (dd, 1H, J(7,6)=8.8, J (7,9)=2.5, H-C(7)); 7.41 (d, 1H, J(6,7)=8.8, H-C(6)). 13 C-NMR (CDCl 3 , δ C ): 153.36 (s, C(1)); 162.12 (s, C(2)); 120.24 (s, C(3)); 147.24 (s, C(4)); 113.49 (c, C(5)); 123.93 (d, C(6)); 112.32 (d, C(7)); 160.64 (s, C(8)); 100.94 (d, C(9)); 23.69 (t, C(10)); 21.27 (t, C(11)); 21.58 (t, C(12)); 25.10 (t, C(13); 66.68 (t, C(14)); 36.11 (t, C(15)); 143.95 (s, C(16)); 118.89 (d, C (17) (7,9)=2.5, H-C(7)); 6.90 (d, 1H, J(9,7)=2.5, H-C(9)); 6.95 (dd, 1H, J (15,17)=2.6, J (15,19)=1.6, H-C(15)); 6.98 (ddd, 1H, J (19,18)=7.6, J (19,15)=1.6, J (19,17)=1.0, H-C(19)); 7.29 (dd, 1H, J (18,17)=8.3, J (18,19)=7. 6, H-C(18)); 7.32 (d, 1H, J(6,7)=9.2, H-C(6)).…”

“…13 C-NMR (CDCl 3 , δ C ): 155.10 (s, C(1)); 161.28 (s, C(2)); 111.74 (d, C(3)); 152.44 (s, C(4)); 113.37 (s, C(5)); 125.21 (d, C(6)); 112.91 (d, C(7)); 161.96 (s, C(8)); 101.75 (d, C(9)); 18.51 (q, C(10)); 71.06 (t, C(11)); 142.96 (s, C(12)); 121.30 (d, C(13)); 31.18 (t, C(14)); 40.70 (d, C(15)); 37.99 (s, C(16)); 43.10 (d, C(17)); 31.39 (t, C(18)); 26.01 (q, C(19)); 20.96 (q, C (20) (18), 3H-C(20)); 5.03 (s, 2H, H-C(11)); 6.12 (q, 1H, J(3,10)=1.2, H-C(3)); 6.63 (s, 2H, H-C(13), H-C(17)); 6.87 (d, 1H, J(9,7)=2.5, H-C(9)); 6.92 (dd, 1H, J(7,6)=8.8, J (7,9)=2.5, H-C(7)); 7.49 (d, 1H, J(6,7)=8.8, H-C(6)). 13 C-NMR (CDCl 3 , δ C ): 155.11 (s, C(1)); 161.06 (s, C(2)); 112.04 (d, C(3)); 152.33 (s, C(4)); 113.76 (s, C(5)); 125.47 (d, C(6)); 112.78 (d, C (7)); 161.50 (s, C(8)); 101.80 (d, C(9)); 18.52 (q, C(10)); 70.64 (t, C(11)); 131.22 (s, C(12)); 104.57 (d, C(13), C(17)); 153.46 (s, C (14), C(16)); 137.96 (s, C(15)); 56.07 (q, C(18), C(20)); 60.72 (q, C (19) …”

“…37 To 0.5 mmol of corresponding compound 11, 12 or 13 in dry ethanol (5 mL) 0.75 mmol of K 2 CO 3 , and 0.75 mmol of bromide (16, 17, (-)-19, (+)- 19,22) were added at r.t. under stirring. The reaction mixture was stirred at r.t. for 15 minutes, and then heated at 60 °C for 5 hours.…”

“…[16][17][18] Furthermore, many researchers are interested in developing new cytotoxic agents from this class of compounds. [19][20][21][22] The molecules of the library were screened to the binding pocket of the crystal structure of Tdp1 (PDB ID: 1MU7, resolution 2.0 Å). 23 From the InterBioScreen natural product library 10179 compounds were used.…”

“…tm, 2H, J(10,11)=6.2, 2H-C(10)); 2.72 (tm, 2H, J(13,12)=6.2, 2H-C(13)); 3.80 (s, 3H-C(21)); 5.07 (s, 2H, 2H-C(14)); 6.84 (d, 1H, J(9,7)=2.5, H-C(9)); 6.85 (ddd, 1H, J(18,19)=8.3, J(18,16)=2.6, J(18,20)=0.9, H-C(18)); 6.88 (dd, 1H, J(7,6)=8.8, J(7,9)=2.5, H-C(7)); 6.95 (dd, 1H, J(16,18)=2.6, J(16,20)=1.6, H-C(16)); 6.98 (ddd, 1H, J(20,19)=7.5, J(20,16)=1.6, J(20,18)=0.9, H-C(20)); 7.28 (dd, 1H, J(19,18)=8.3, J(19,20)=7.5, H-C(19)); 7.43 (d, 1H, J(6,7)=8.8, H-C(6)). 13 C-NMR (CDCl 3 , δ C ): 153.33 (s, C(1)); 161.97 (s, C(2)); 120.58 (s, C(3)); 147.07 (s, C(4)); 113.89 (s, C(5)); 124.01 (d, C(6)); 112.48 (d, C(7)); 160.31 (d, C(8)); 101.65 (d, C(9)); 23.73 (t, C(10)); 21.57 (t, C(11)); 21.28 (t, C(12)); 25.10 (t, C(13)); 70.13 (t, C(14)); 137.53 (s, C(15)); 112.83 (d, C(16)); 159.81 (s, C(17)); 113.59 (d, C(18)); 129.66 (d, C(19)); 119.49 (d, C(20)); 55.14 (q, C(21)).…”