Sodwanones G, H, and I, New Cytotoxic Triterpenes from a Marine Sponge

Abstract

Three cytotoxic triterpenes, sodwanones G [5], H [6], and I [7], have been isolated from a marine sponge. The three structures were determined by interpretation of nmr spectra, and in the case of 5, also on the basis of the X-ray diffraction analysis. The X-ray diffraction analysis of two other earlier reported sodwanones, E [3] and F [4] is also discussed. The cytotoxic activity against several cancer cell lines, has been tested. IC50 values between 20 and 0.02 microM were obtained. Compounds 5 and 6 were 10- and 500-fold, respectively, more cytotoxic to A-549 cells than to any of the other cell lines tested (HT-29, MEL-28, P-388).

Sodwanone and Yardenone Triterpenes from a South African Species of the Marine Sponge Axinella Inhibit Hypoxia-Inducible Factor-1 (HIF-1) Activation in Both Breast and Prostate Tumor Cells

“…Comparison of the 1 H and 13 C NMR spectra of 9 (Table 1 and 2) with those of known sodwanones suggested that 9 had the same tricyclic C-2 -C-11 system as in sodwanone S 20 and the C14-C18 epoxide-bridged C14-C19 cyclohexane ring and C-19 substituted side chain (C20 -C31) that were previously reported for the structure of sodwanone I. 21 Analysis of the COSY and HMQC spectra of 9 confirmed these partial structures and facilitated the deduction of the six partial structures:…”

“…Comparison of the 1 H and 13 C NMR spectra of 9 (Table 1 and 2) with those of known sodwanones suggested that 9 had the same tricyclic C-2 -C-11 system as in sodwanone S 20 and the C14-C18 epoxide-bridged C14-C19 cyclohexane ring and C-19 substituted side chain (C20 -C31) that were previously reported for the structure of sodwanone I. 21 Analysis of the COSY and HMQC spectra of 9 confirmed these partial structures and facilitated the deduction of the six partial structures: [-CH(3)-CH 2 (4)-CH (5) (Table 2) showed carbon resonances for two keto-carbonyls (δ C 217.9 and 216.0) and seven other oxygen-substituted carbon resonances, three of which were quaternary carbons (δ C 92.5, 82.6, 81.6) and four were methines (δ C 82.8, 81.9, 77.5, 74.4). The 1 H NMR spectrum of 10 (Table 1) showed the presence of seven tertiary methyl groups and one methyl resonance at δ H 1.08 (d, J = 6.5 Hz).…”

“…Certain sodwanones have been proposed to be generated via cyclization of unstable epoxide intermediates. 20 It remains possible that a such structurally related unstable analog(s) is responsible for the potent HIF-1 inhibitory activity and that, many if not most, of the sodwanone triterpenes isolated from various collections of Axinella species actually represent degradation artifacts.DaiCell line-dependent cytotoxicity has been reported for sodwanones A, G, H, and S. 15,[20][21][22] The effect of 1-11 on tumor cell proliferation/viability was examined in T47D and MDA-MB-231 breast tumor cells and in PC-3 and DU145 prostate tumor cells. Following 48 hr incubation under normoxic conditions (95% Air:5% CO 2 ), 2 inhibited T47D cell proliferation/viability with an IC 50 of 22 μM and 8 inhibited MDA-MB-231 cells with an IC 50 of 23 μM.…”

Unusually cyclized triterpenes: occurrence, biosynthesis and chemical synthesis

“…Structurally related to sipholanes and siphonellines, neviotine B (138) and dahabinone A (139) are, respectively, pentacyclic and tetracyclic triterpenes isolated from S. siphonella. 100 A number of sodwanones have been found to possess cytotoxic activity against different cell lines. Six new sodwanones (140-145) were isolated from the marine sponge Axinella weltneri and seven from an unnamed species of Axinella collected in the Indo-Pacific (146-152).…”

Triterpenoids as Anticancer Drugs from Marine Sponges

“…The compounds have shown cytotoxicityactivity against cell cultures of P-388 murine leukemia, A-549 human lung carcinoma, HT-29 human colon carcinoma, and MEL-28 human melanoma. Sodwanones G (46), H (47), I (48) showed high specificity towards human lung carcinoma cell line A-549, where the specificity of sodwanone G was prominent (46) [28]. The cytotoxic triterpenes, sodwanones K(49), L (50), and M (51) were found to be cytotoxic to P-388 murine leukemiacells [29].…”