Macrocyclic bis-quinolizidine alkaloids from Xestospongia muta

Abstract

A new stereoisomer Meso-araguspongine C together with nine reported macrocyclic bis-quinolizidine alkaloids araguspongines A, C, E, L, N-P, petrosin, and petrosin A were isolated from marine sponge Xestospongia muta. Stereochemistry of meso-araguspongine C (2) and araguspongines N-P (3-5) were established by their NMR data and conformational analyses. Both araguspongine C (1) and meso-araguspongine C (2) exhibited great cytotoxic activity towards HepG-2, HL-60, LU-1, MCF-7, and SK-Mel-2 human cancer cells (IC in the range of 0.43-1.02 μM). At a concentration of 20 μM, isolated compounds (1-10) also showed modest inhibitory effects (from 7.6 to 40.8%) on the NO production in LPS activated RAW264.7 macrophages.

Marine-Derived Macrocyclic Alkaloids (MDMAs): Chemical and Biological Diversity

“…Xestosin A (16), another bis-quinolizidine-containing macrocycle, was isolated from the Papua New Guinean sponge Xestospongia exigua [22]. Compounds 12 and 13, isolated from Xestospongia muta, did not show growth inhibition against LU-1 (lung), HepG-2 (liver), HL-60 (leukemia), MCF-7 (breast), and SK-Mel-2 (melanoma) human cancer cells [20]. However, compounds 12, 13, and 15 exhibited vasodilative activity, and 12 and 13 were two-fold more active than papaverine [19].…”

“…Xestospongins/Araguspongines Araguspongines (xestospongins) are a class of macrocyclic alkaloids consisting of a 20-membered ring and two 1-oxaquinolizidine moieties. Xestospongins A (araguspongine D) (17), B (18), C (araguspongine E) (19), and D (araguspongine A) (20) were isolated from the Australian sponge Xestospongia exigua and from Xestospongia sp. [17,23], whereas xestospongins E-J (21-26) ( Figure 5) were isolated from the sponge Oceanapia sp.…”

“…Three compounds, identified as LT-9 (41), LT-10 (42), and LT-6 (43) ( Figure 5), were isolated from the Thai water sponge Xestospongia sp. ; however, their structures were clarified and renamed as araguspongines N−P (41)(42)(43) [20,35]. Araguspongines A, B, C, F, G, H, and J (20, 31, 32, 33, 34, 35, and 36) and M-P (40-43) possess bis-1-oxaquinolizidine moiety, whereas 38 and 39 have a bis-1-oxaquinolizidine N-oxide moiety [17,33].…”

“…Dung et al reported the isolation of meso -araguspongine C ( 44 ) from the sponge Xestospongia muta . Compounds 32 and 44 showed significant cytotoxic activity against LU-1, HepG-2, HL-60, MCF-7, and SK-Mel-2 human cancer cells, with IC 50 values ranging from 0.43 to 1.02 μM; however, 44 is more potent than 32 [ 20 ]. Compounds 20 , 32 , 38 , and 39 exhibited cytotoxicity against breast cancer BT-474 cells, with IC 50 values of 9.3, 15.2, 29.5, and 35.6 μM, respectively [ 37 ].…”

The chemical constituents and biological activity of some sponges in Northern Vietnam: A review

“…From the sponge X. muta, eleven alkaloid compounds of bisquinolizidine form with a large ring structure have been isolated quinolizidine with large ring structure has been isolated (91-101). [38,39] These compounds are formed by a large closed loop connection between either quinolizidine or 1-oxaquinolizidine units via two linear carbon sequences 5C or 6C. Among them, compound 92 is a novel compound, and its chemical structure is defined as the meso isomer of compound 91.…”