Fifteen novel glycyrrhetinic acid derivatives containing a nitrogen heterocycle at C-30 and with different A-ring substituents were designed and synthesized. All of these derivatives have improved antiproliferative effects against human HL-60 leukemia cells. Compounds with a cyano-enone functionality on the A-ring exhibit greater growth inhibitory effects, compared to those with a 2-hydroxymethylene-3-keto, an isoxazole, or a 2-cyano-3-keto group. N-(2-cyano-3,11-dioxoolean-1,12-dien-30-yl)-4-piperidyl piperidine (9 b) was found to be two-fold more potent than methyl 2-cyano-3,11-dioxooleana-1,12- dien-30-oate(CDODO-Me-11).

Psammaplin F, an unsymmetrical disulfide bromotyrosine, was isolated from the sponge Pseudoceratina purpurea in 2003. We reported here the first total synthesis of psammaplin F in 12% overall yield by employing Cleland’s reagent reduction as key step. The longest linear synthetic sequence starting from 3-bromo-4-hydroxybenzaldehyde and hydantoin was seven steps. In addition, a detailed X-ray crystal structure analysis of psammaplin A analogue 8b is given for the first time.

A series of novel substituted 1,2,3-benzotriazines based on the structures of vatalanib succinate (PTK787) and vandetanib (ZD6474) were designed and synthesized. The antiproliferative effects of these compounds were tested on microvascular endothelial cells (MVECs) using the MTT assay. Introduction of a methoxy and a 3-chloropropoxy group into the 1,2,3-benzotriazines increased the antiproliferative effects. 4-(3-Chloro-4- fluoroanilino)-7-(3-chloropropoxy)-6-methoxy-1,2,3-benzotriazine (8m) was the most effective compound. It was 4-10 fold more potent than PTK787 in inhibiting the growth of T47D breast cancer cells, DU145 and PC-3 prostate cancer cells, LL/2 murine Lewis lung cancer cells and B16F0 melanoma cells.

Seventeen novel 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate and -carboxamide derivatives were synthesized and evaluated for their growth inhibition in seven human solid tumor and a human leukemia HL-60 cell lines. Compound IVa showed more activity than the other compounds and the positive control temozolomide. In the presence of 40 mg/mL of IVa, the survival rate of all tested tumor cells was less than 10%. Esters displayed more potent antitumour activity than amides and temozolomide against HL-60 cells. These compounds also exhibited considerably enhanced water-solubility.