Anti-tumor agents 255: Novel glycyrrhetinic acid–dehydrozingerone conjugates as cytotoxic agents

Abstract

Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anti-cancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED(50) values of 0.6, 0.8, and 0.9 microM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anti-cancer drug discovery and development.

Synthesis and biological evaluation of novel conjugates of camptothecin and 5-flurouracil as cytotoxic agents

“…On the basis of this theory, some interesting results have been reported by our group as well as others in recent years. [3][4][5][6][7] In our prior study, Vol. 22, No.…”

Synthesis and Anti-inflammatory Activity of Novel Benzimidazole (Benzothiazole) Phenylursolate

“…熊果酸即 3β-羟基-熊果-12-烯-28-酸(3β-hydroxyurs-12-en-28-oic acid, UA, 1)属于 α-香树脂醇(α-amyrin) 型五环三萜类化合物, 具有抗炎 [1,2] 、抗癌 [3,4] 、抗菌 [5] 等生物活性, 且毒副作用较小. 但其脂溶性和水溶性均 比较差, 不易透过生物膜, 故与同类临床药物相比其药 效明显偏低 [6] .…”

Synthesis and antitumor activity of 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline-5-phenylursolate and 4-chalcone ursolate derivatives

“…In past decades, UA has attracted considerable interest owing to its significant biological activities and promising clinical application as a chemotherapeutic and chemopreventive agent. Indeed, UA exhibits attractive pharmacological properties, including anti-inflammatory activity [1, 2], anti-HIV [3], anti-malarial [4], anti-microbial [5], anti-melanoma [6], and antitumor [7][8][9][10][11].The conjugation of two bioactive compounds is now accepted as an effective strategy for designing ligands, inhibitors, and other drugs [8]. Chalcones, which belong to the flavonoid compounds, exhibit antioxidant and anti-inflammatory properties and have recently attracted attention also for their antitumor activity in preclinical models [12, 13].…”

“…In past decades, UA has attracted considerable interest owing to its significant biological activities and promising clinical application as a chemotherapeutic and chemopreventive agent. Indeed, UA exhibits attractive pharmacological properties, including anti-inflammatory activity [1, 2], anti-HIV [3], anti-malarial [4], anti-microbial [5], anti-melanoma [6], and antitumor [7][8][9][10][11].…”

“…The conjugation of two bioactive compounds is now accepted as an effective strategy for designing ligands, inhibitors, and other drugs [8]. Chalcones, which belong to the flavonoid compounds, exhibit antioxidant and anti-inflammatory properties and have recently attracted attention also for their antitumor activity in preclinical models [12, 13].…”