Cytotoxic Taccalonolides and Withanolides from Tacca chantrieri

Abstract

Six new taccalonolides, taccalonolides AT-AY (1-6), and two new withanolides, chantriolides D and E (7 and 8), together with ten known compounds (9-18), have been isolated from whole plants of Tacca chantrieri. The structures, including the absolute configurations of some of the compounds, were determined by spectroscopic and chemical methods. All compounds were evaluated for their in vitro cytotoxicity against five tumor cell lines. Compounds 9, 10, 13-15, and 17 exhibited cytotoxic activity, with IC50 values of 1.13-5.71 µM, while compound 7 showed selective cytotoxicity. The results indicated that taccalonolides with a six-membered lactone moiety located at C-15 and C-24 were devoid of cytotoxicity against five tumor cell lines (> 10 µM).

Taccalonolides: The Potential Next Generation of Microtubule-Stabilizing Anticancer Agents

“…This reaction allowed the semi-synthesis of epoxide derivatives (< 1 mg) of rare natural taccalonolides, which confirmed the finding that epoxidation of the C22-23 double bond is an effective way to increase the potency of this class of molecules (Table 3 and Figure 4) [41]. In contrast, the rearrangement of γ-lactone to δ-lactone in the case of taccalonolides AO, AK, and AT-AY and the presence of an αhydroperoxyl group at C20 of taccalonolide AC led to the lack of cytotoxicity and microtubule-stabilizing activities [23,31]. It can be concluded that the E-ring region of taccalonolides is critical for microtubule-stabilizing activities (Figure 5).…”

“…Withanolides are a large group of steroidal lactones with a wide range of pharmacologic properties found in the Indian medicinal plant Withania somnifera. They are also found in plants of many www.videleaf.com members of the family Solanaceae and in the genus Tacca [19,20,23]. The common feature of withanolides is an intact or rearranged ergostane with a highly structural diverse side chain (Figure 3).…”

“…The pathways for withanolide biosynthesis have been well-studied in particular for the arrangement of the side chain in recent years [24][25][26]. Though no genes or enzymes specifically responsible for taccalonolides biosynthesis have been characterized to date, the fact that taccalonolides, perulactones, and withanolides are co-isolated from various plants suggesting that they share the same upstream biosynthetic pathway [21,23,27]. [16,30,41].…”

Antitrypanosomal Activity of a Novel Taccalonolide from the Tubers of Tacca leontopetaloides

“…Additionally, the tubers are used to treat stomach disorders, mainly diarrhoea and dysentery (Ukpabi et al, 2009). Over 134 compounds with different bioactivities have been isolated from Tacca species comprising of steroids, terpenoids, diaryheptanoids and taccalonolides (Chen et al, 1987(Chen et al, , 1988a(Chen et al, , 1988bYokosuka et al, 2002;Mühlbauer et al, 2003;Jiang et al, 2014;Ni et al, 2015). The first taccalonolide was isolated over five decades ago from the tubers of Tacca leontopetaloides when the "bitter principle" of the plant characterised as taccalin was being examined (Chen et al, 1987).…”

Potential Anticancer Properties and Mechanisms of Action of Withanolides

“…Withanolide E (WE) enhanced death receptor-mediated apoptotic signaling in renal carcinoma cells by a rapid decline in the levels of cFLIP protein due in part to apparent reduced stability leading to its degradation [27]. Two novel withanolides, chantriolides D and E, together isolated from Tacca chantrieri, where chantriolide D showed selective cytotoxicity against cancer cells [28]. Sixty-five withanolides with antiproliferative activity were isolated from Datura wrightii, Jaborosa caulescens, Physalis hispida, Physalis longifolia, and V. breviflora [29].…”