New Steroids and a New Alkaloid from the Gorgonian Isis minorbrachyblasta: Structures, Cytotoxicity, and Antilarval Activity

Abstract

Two new polyoxygenated steroids, (1a,3b,7a,11a,12b)-gorgost-5-ene-1,3,7,11,12-pentol 12-acetate (1) and 11-O-acetyl-22-epihippuristanol (2), and a new alkaloid, 2,3,5,6,11,11b-hexahydro-2-hydroxy-1H-indolizino [8,7-b]indole-2-carboxylic acid (3), together with three known compounds, 22-epihippuristanol (4), hippuristanol (5), and tryptamine (6), were isolated from the EtOH/CH 2 Cl 2 extracts of the South China Sea gorgonian Isis minorbrachyblasta. The structures of the new compounds were determined by spectroscopic methods. Compound 1 showed weak cytotoxicity against A549, HONE1, and HeLa cancer cell lines and strong antilarval activity towards Bugula neritina larvae with an EC 50 value of 5.8 mg/ml. Compound 5 showed moderate cytotoxicity against A549, HONE1, and HeLa cell lines, and the epimer mixture 4/5 (weight ratio 3 : 2) exhibited potent cytotoxicity against A549 and HONE1 cell lines with IC 50 values of 4.2 and 4.8 mg/ml, which indicated that epimers 4 and 5 might have a synergistic effect on their cytotoxicity against A549 and HONE1 cell lines.Introduction. -Both Isis minorbrachyblasta and I. hippuris belong to the Isis genus, Isididae family of gorgonian corals. There are reports that I. hippuris is unique concerning its steroidal constituents that can be characterized as of the hippurin or hippuristanol type having a spiroketal [1 -4], of the gorgosterol type possessing a cyclopropane [5 -7], and of the hippuristerone type containing a 3-keto function [4] [8]. These types also differ in the side-chain alkylation pattern. Some of these compounds have been reported to have significant biological activities, e.g., hippuristanol and (2a)-2-hydroxyhippuristanol showed 50% inhibition (in vitro) of DBA/MC fibrosarcoma at 0.8 and 0.1 mg/ml [2], several hippuristanol-type steroids showed potent cytotoxicity against P-388, A549, HT29, and MEL28 cancer cell lines [4], and several gorgosterol-type steroids showed moderate activity against drug-resistant cells (KBC2) expressing P-glycoprotein [7]. However, there were no reports about the chemical constituents of Isis minorbrachyblasta. In our present investigation on the chemical constituents of the South China Sea gorgonian I. minorbrachyblasta Zou 1991, two new steroids, (1a,3b,7a,11a,12b)-gorgost-5-ene-1,3,7,11,12-pentol 12-acetate (1) and 11-O-acetyl-22-epihippuristanol (2), and a new alkaloid, 2,3,5,6,11,11b-hexahydro-2-hydroxy-1H-indolizino [8,7-b]indole-2-carboxylic acid (3), were obtained, together with the three known compounds 22-epihippuristanol (4) [4], hippuristanol (5) [2] [4], and tryptamine (6) [9]. The cytotoxicity of 1, 5, and the

Marine Indole Alkaloids

“…and showed antibacterial activity against Bacillus subtilis , Staphylococcus aureus , Escherichia coli and Vibrio alginolyticus ( Figure 144 ) [ 334 ]. 2,3,5,6,11,11 b -Hexahydro-2-hydroxy-1 H -indolizino[8,7- b ]indole-2-carboxylic acid ( 786 ) was isolated from extracts of the South China Sea gorgonian Isis minorbrachyblasta [ 335 ]. Examination of the Australian marine sponge Ancorina sp.…”

Antifouling Compounds from Marine Invertebrates

“…Compound 120 was a 5a-hydroxylated analog of 115 , having similar AF activity against B. neritina larvae and B. amphitrite larvae [ 51 ]. 1α,3β,7α,11α,12β)-Gorgost-5-ene-1,3,7,11,12-pentol 12-acetate ( 121 ) from the gorgonian Isis minorgrachyblasta inhibited the settlement of B. neritina larvae with EC 50 value of 4.8 μg/mL and LC 50 >100 μg/mL [ 54 ]. Four 24-ketal steroids ( 122 – 125 ) from the gorgonian S. mollis showed AF activity against B. amphitrite larvae at nontoxic concentrations with EC 50 values of 0.81–7.91 μg/mL [ 39 ].…”

Chemical Review of Gorgostane-Type Steroids Isolated from Marine Organisms and Their 13C-NMR Spectroscopic Data Characteristics

“…5β,6β-Epoxygorgosterol (23) [26] is the parent compound of this group, which has only one hydroxyl group at C-3. 5β,6β-Epoxygorgostane-1α,3β,11α,12β-tetrol (24) [23] has a trihydroxy substitution at C-1, C-11, and C-12 with chemical shifts 73.8, 73.8, and 83.6 ppm, respectively. 5β,6β-Epoxygorgostane-3β,11α,12β-triol 12-acetate (25) [22] has a hydroxyl group at C-11, in addition to an acetoxy group at C-12, and the chemical shifts of C-11 and C-12 is 73.2 and 85.1 ppm, respectively.…”

“…5β,6β-Epoxygorgostane-3β,11α,12β-triol 12-acetate (25) [22] has a hydroxyl group at C-11, in addition to an acetoxy group at C-12, and the chemical shifts of C-11 and C-12 is 73.2 and 85.1 ppm, respectively. Isihippurol B (26) [27] is the same as compound (24) except for the presence of an acetoxy group at C-12. The chemical shift is more downfield from 83.6 to 86.2 ppm.…”