Cytotoxic ent-Kaurane Diterpenoids from Isodon eriocalyx var. laxiflora

Abstract

Three new ent-kaurane diterpenoids laxiflorin E (1), laxiflorin H (6) and laxiflorin I (8) were isolated from the leaves of Isodon eriocalyx var. laxiflora, along with nine known diterpenoids, eriocalyxin A (2), laxiflorin C (3), laxiflorin D (4), laxiflorin A (5), maoecrystal S (7), maoecrystal Q (9), eriocalyxin B (10), maoecrystal C (11) and enmelol (12). The structures of the new compounds were determined by spectroscopic methods. Compounds 1-5 are 6,7-seco-ent-kaurane-7,20-olide diterpenoids, and 6-12 belong to 7,20-epoxy-ent-kauranoids. The spectral data of enmelol (12) are reported here for the first time. Ten of these compounds were tested for their cytotoxicity toward K562 and T24 human tumor cells. Compounds 1, 3 and 10 showed significant inhibitory effects on K562 cells with IC50 values 0.077, 0.569 and 0.373 microg/mL, and compounds 1 and 10 also demonstrated significant inhibitory activities toward T24 cells with IC50 values 0.709 and 0.087 microg/mL. Compounds 8 and 11 also displayed inhibitory effect on both two kinds of cells with IC 50 value less than 6.5 microg/mL.

Four new diterpenoids from Isodon eriocalyx var. laxiflora

“…laxiflora, and its structure was confirmed by NMR and single-crystal X-ray diffraction in 2002. 15 The molecular formula of compound 4 was determined to be (Figure 3) (for the observed proton spin systems, H-9/H 2 -11/H 2 -12/H-13/H 2 -14, H 2 -1/H 2 -2/H 2 -3, and H-5/H 2 -6/H-7) confirmed this result. Based on detailed analysis of ROESY data, the relative configuration of the stereogenic centers in compound 4 were determined to be the same as those in laxiflorin O (5).…”

“…The analysis of the 13 C NMR and DEPT spectra (Table 2) revealed the presence of 24 carbons, which were assigned as three methyls (δ C 29.9, δ C 24.1, and δ C 29.7), six methylenes (one oxygenated at δ C 65.6), seven methines (one oxygenated at δ C 73.5 and two olefinic groups at δ C 127.4 and δ C 160.7), and eight quaternary carbons (one hemiacetal at δ C 96.3 and four carbonyls at δ C 197.4, δ C 225.2, δ C 207.5, and δ C 206.1), which suggested that 1 is a highly oxygenated diterpenoid with a C 24 skeleton similar to the ent-kaurane skeletons previously reported. 4,9 Comparison of the NMR spectral data of 1 with those of eriocalyxin B (6) 16 revealed that 1 was consistent with *To whom correspondence should be addressed. E-mail: pujianxin@mail.kib.ac.cn (J.X.…”

“…4,5 As one of the important plants of Isodon genus, I. eriocalyx var. laxiflora has been investigated phytochemically as it is a rich source of diterpenoids, such as 7,20-epoxy-ent-kauranoids (laxiflorins H and I), 6 3,20-epoxy-ent-kauranoids (laxiflorins J-M), 7,8 6,7-seco-ent-kauranoids (laxiflorins A-C), 9 6,7:8,15-seco-ent-kauranoids (laxiflorins F and G), 10 ent-abietanoids (laxiflorin N), 11 15,16-seco-16,17-dinor-ent-kauranoids (neolaxiflorins D-F) 12 , two unprecedented epimeric bishomoditerpene lactones with a unique C 22 framework (laxiflorolides A and B), 13 and two unprecedented ent-kaurane diterpenoids (neolaxiflorins A and B).…”

“…14 Our further investigation of this plant led to the isolation of four novel ones, laxiflorins S-V (1-4), and one known compound, laxiflorin O (5) 15 ( Figure 1). These new compounds could be classified into 4 different types as below: tetrahomo-7,20-epoxy-ent-kauranoid (1), 7,20-epoxy-ent-kauranoid (2), 15,16-seco-16,17-dinor-entkauranoid (3), and 3,4-seco-ent-abietane diterpenoid (4), respectively.…”

Chemical constituents from the fungus Ganoderma tropicum (Jungh.) Bres. and their cytotoxic activities

“…Briefly, cells were placed in 96-well plates 12 h before treatment with initial density of 5000 cells/well and continuously exposed to different concentrations (40, 8, 1.6, 0.32, and 0.064 mol.L -1 ) of compounds for 48 h, with cisplatin (Sigma, USA) as the positive control. Inhibition rates of cell proliferation after compound treatment were determined by MTT assay, as described previously (Niu et al, 2002;Monks et al, 1991), and IC 50 calculated with Reed and Muench method (Reed and Muench, 1938).…”