A Heterodimeric Glucuronide Prodrug for Cancer Tritherapy: the Double Role of the Chemical Amplifier

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

“…The conjugated curcumin is water soluble and could therefore be administered to patients intravenously at dosages that yield higher blood concentrations than when curcumin is given orally. If the conjugates are sufficiently taken up by cancer cells, as has been shown for various glucuronide adducts of anticancer agents such as doxorubicin (de Graaf et al, 2004;Grinda et al, 2011) and anthracycline prodrugs (Houba et al, 1996;Bakina et al, 1997), the conjugates could be cleaved by intracellular b-glucuronidases and sulfatases (Fig. 12) to yield curcumin and impart a pharmacological effect directly in the tumor cells.…”

Linker Hydrophilicity Modulates the Anticancer Activity of RGD–Cryptophycin Conjugates

“…The corresponding benzylic alcohol was treated with tert ‐butyldimethylsilyl chloride and imidazole to produce the silyl ether protected derivative 9 (93 %). At this stage, as reported by Grinda et al., the protecting groups of the β‐glucuronide were modified via a three‐step strategy to yield the fully allyl‐protected carbohydrate ( 12 ) [50] . This methodology offers a stable and compatible glucuronide protection in the course of the synthesis, while the deprotection can be performed in a one‐step procedure under mild conditions at the end of the synthesis.…”

“…At this stage, as reported by Grindae tal.,t he protecting groups of the b-glucuronide were modified via at hree-step strategy to yield the fully allylprotectedc arbohydrate (12). [50] This methodology offers a stable and compatible glucuronide protectioni nt he course of the synthesis, while the deprotection can be performed in a one-step procedure under mild conditions at the end of the synthesis. The acetyl groupsw ere removed from 9 using sodium methoxide to afford the hydroxy-free derivative 10 (84 %).…”

Antineoplastic Agents. 600. From the South Pacific Ocean to the Silstatins

“…Using the strategy followed for the preparation and purification of 3a, unit 9 (376 mg, 0.87 mmol) was coupled to Fmoc-Tyr(OtBu) (441 mg, 0.96 mmol) using DCC (198 mg, 0.96 mmol) and DMAP (32 mg, 0.26 mmol) in 10 mL of anhydrous DCM. After separation by column chromatography 10b was obtained as a colorless solid: yield 90% (688 mg, 0.79 mmol); TLC R f 0.25 (1:4 EtOAc/hexanes); mp 52−56°C; [α] 24 D +11.2 (c 0.17, CHCl 3 ); 1 H NMR (CDCl 3 , 400 MHz) δ 7.74 (2H,d,J = 7.6 Hz),7.57 (2H,t,J = 7.6 Hz),7.39 (2H,t,J = 7.2 Hz),7.33 (7H,m),7.06 (2H,d,J = 8.4 Hz),6.90 (2H,d,J = 8.4 Hz),6.83 (1H,d,J = 8.4 Hz),5.45 (1H,d,J = 7.6 Hz) 1, 170.6, 170.2, 170.1, 156.0, 154.7, 143.7, 141.3, 135.2, 130.3, 129.7, 128.6, 128.4, 128.2, 127.8, 127.1, 125.1, 124.2, 120.0, 78.5, 73.3, 69.3, 67.3, 67.1, 57.3, 55.5, 47.1, 39.4, 36.9, 33.8, 33.7, 32.4, 30.8, 28.9, 26.4, 26.1, 26.0, 19.1, 18. Fmoc-[Val-D-Hcha-D-Val-Lac] 2 -OBn (12). Using the experimental strategy followed for the preparation and purification of 5, unit 10a (300 mg, 0.40 mmol) was deprotected with 2,2′,2″-triaminotriethylamine (605 μL, 588 mg, 4.00 mmol) in 10 mL of DCM and then coupled to unit 11a (266 mg, 0.40 mmol) using HBTU (303 mg, 0.80 mmol) and TEA (55 μL, 40 mg, 0.40 mmol) in 5 mL of anhydrous DMF.…”