Hederagenin as a triterpene template for the development of new antitumor compounds

Abstract

In this study, a series of novel C-28 esters and amides derivatives of hederagenin (He) were designed and synthesized in attempt to develop potent antitumor agents. Their structures were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. Although most of the compounds displayed moderate to high levels of cytotoxic activity they were all more potent than the natural product He. The most active compounds had either an ethylpyrimidinyl (27) or an ethylpyrrolidinyl (28) substituent, with EC50 in the range of 1.1-6.5 μM for six human cancer cell lines. Notably, this corresponds to an approximately 30-fold times greater potency than He.

Current knowledge and development of hederagenin as a promising medicinal agent: a comprehensive review

“…HG has been shown to have a wide range of potential anti-tumor effects both in vitro and in vivo, which have been evaluated in various types of cancers, including lung, colon, stomach, liver, ovarian, prostate, breast, and endometrial cancers. 2,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Table 4 summarizes the anti-tumor activity of HG in different tumor cell lines and animal models. Considerable attention has been devoted to the anti-tumor effect of HG in many tumor cell lines.…”

“…3) possessing m-bromo, m-chloro, and m-nitro substituents, respectively, were the most active of the triazolyls with EC 50 values in the range of 3.0-4.1 mM toward all cell lines, and were at least 8 times more active than HG. 17,18 In another study by the same investigator, HG was converted into several 1,2,3triazolyl derivatives at both the C-23 and C-28 positions. Compound 8 (Fig.…”

“…4 In recent years, HG has been observed to be biologically active, as well as many other saponins with similar structures, such as ursolic acid and corosolic acid. HG exhibits multiple pharmaceutical and biological activities, including antitumor, 2,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] anti-inammatory, [24][25][26][27][28][29][30] anti-depressant, [31][32][33][34][35] antineurodegenerative, [36][37][38] anti-hyperlipidemia, 4,39,40 anti-diabetic, [41][42][43] anti-leishmanial, 19,44,45 and anti-viral (against hepatitis B) activity. 46 Recently, a number of studies have investigated the use of HG as a potential anti-tumor agent.…”

“…46 Recently, a number of studies have investigated the use of HG as a potential anti-tumor agent. 5,6,[10][11][12][14][15][16] The pharmacokinetics, [47][48][49][50][51] structural modication, [17][18][19][20][21]35,38,45,46 and mechanisms of action [4][5][6][10][11][12][13][14][15][16]19,25,26,[31][32][33][34]36,37,39,40,43,45 of HG have also been studied. However, possibly owing to limited in vivo data, HG is still in the preclinical development stage.…”

Development and validation of a quantification method for oleanolic acid and hederagenin in rat plasma: application to the pharmacokinetic study

“…, ). Oleanolic acid and hederagenin are the active triterpenoid compounds of this herbal drug, which demonstrates various pharmacological effects, such as anti‐inflammation, anti‐allergy, antitumor and neuroprotective effects (Oh et al ., ; Martín et al ., ; Caltana, Rutolo, Nieto, & Brusco, ; Rodríguez‐Hernández, Demuner, Barbosa, Csuk, & Heller, ; Lee et al ., ). Moreover, both compounds serve as content determination indices for the quality control of this plant in the Chinese Pharmacopoeia (State Pharmacopoeia Commission of P.R.…”