Krempfielins N–P, New Anti-Inflammatory Eunicellins from a Taiwanese Soft Coral Cladiella krempfi

Abstract

Three new eunicellin-type diterpenoids, krempfielins N–P (1–3), were isolated from a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compound 3 exhibited activity to inhibit superoxide anion generation. Both 1 and3, in particular 1, were shown to display significant anti-inflammatory activity by inhibiting the elastase release in FMLP/CB-induced human neutrophils.

Marine natural products

“…(cladieunicellin J, 1191), 732 Klyxum molle (klymollins T-X, 1192-1196), 733 Cladiella sp. (cladieunicellin M-Q, 1197-1201), 734 Cladiella kremp (krempelins N-R, 1202-1206), 735,736 and Cladiella hirsuta (hirsutalin N-R, 1207-1211). 737 Readers should note that cladieunicellin N 1198 is a structural duplicate of the previously reported Klyxum molle metabolite klymollin Q, 738 exhibiting identical spectroscopic, spectrometric and chiroptical properties and that the structure elucidation of cladieunicellin M-Q also led to revision of conguration at C-7 of the structure of litophynin I diacetate to that shown in 1212.…”

Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…[185][186][187]; two new briarane diterpenoids briaviolides E and I (170,171), isolated from the Taiwanese soft coral Briareum violacea [188]; a new pigmented phenazine compound dermacozine H (172), isolated from the actinomycete Dermacoccus abyssi sp. nov. strain MT1.1, isolated from a Mariana Trench sediment at a depth of 10,898 m [189]; a novel sesquiterpene dysifragilone A (173), isolated from the South China Sea sponge Dysidea fragilis [190]; a new xenicane 4α-hydroxypachylactone (174), isolated from a Chinese brown alga Dictyota plectens [191]; a polyketide comaparvin (175), isolated from the Taiwanese marine crinoid Comanthus bennetti [192]; two novel eunicellin-type diterpenoids hirsutalins N and S (176, 177) and a new tocopherol-derived metabolite hirsutocospiro A (178), isolated from the Taiwanese soft coral Cladiella hirsuta [193][194][195]; a new cembranoid isosinulaflexiolide K (179), isolated from cultured Taiwanese soft corals Sinularia sandensis and Sinularia flexibilis [196]; a novel 9,11-secogorgosteroid klyflaccisteroid F (180), isolated from the Taiwaneses soft coral Klyxum flaccidum [197]; new eunicellin-type diterpenoids krempfielins N (181), Q (182), and R (183), isolated from a Taiwanese soft coral Cladiella krempfi [198,199]; a methylfarnesylquinone (184), isolated from the Taiwanese marine brown alga Homeostrichus formosana [200]; a novel steroid monanchosterol B (185), isolated from the Korean sponge Monanchora sp. [201]; a oxygenated steroid derivative (186), isolated from the Vietnamese starfish Protoreaster nodosus [202]; a new spirobisnaphthalene rhytidenone C (187), isolated from an extract of a cultured fungal endophyte Rhytidhysteron sp.…”

“…As shown in Table 2 and Figure 2, in 2014-2015, the preclinical marine nervous system pharmacology of compounds (196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207)(208)(209)(210)(211) described several mechanism of action: at the nicotinic acetylcholine receptor and potassium channels, with conopeptides, and in models of antinociception and neuroprotection.…”

“…Two studies reported marine compounds (198,200) that contributed to nociceptive pharmacology. Cavalcante-Silva and colleagues assessed the mechanism involved in in vivo antinociception produced by the bisindole alkaloid caulerpine (198), isolated from the marine alga Caulerpa, demonstrating that, in the in vivo murine writhing test, the effect was likely mediated by "pathways involving α2-adrenoceptors and 5-HT3 receptors", thus proposing cualerpine as a possible "dual-action analgesic drug(s)" [214].…”

“…Two studies reported marine compounds (198,200) that contributed to nociceptive pharmacology. Cavalcante-Silva and colleagues assessed the mechanism involved in in vivo antinociception produced by the bisindole alkaloid caulerpine (198), isolated from the marine alga Caulerpa, demonstrating that, in the in vivo murine writhing test, the effect was likely mediated by "pathways involving α2-adrenoceptors and 5-HT3 receptors", thus proposing cualerpine as a possible "dual-action analgesic drug(s)" [214]. Chen and colleagues investigated the anti-neuropathic properties of the antimicrobial peptide piscidin (200) and observed that the compound demonstrated in vivo anti-nociceptive effects in a rat model of neuropathy by a signaling mechanism that suppressed up-regulation of interleukin-1 in microglia and phosphorylated mammalian target of rapamycin in astrocytes, concluding it "may have potential for development as an alternative pain-alleviating agent" [216].…”