The structures and stereochemistry of cytotoxic sesquiterpene quinones from dactylospongia elegans

Rodrı́guez, Jaime; Quiñoá, Emilio; Riguera, Ricardo; Peters, Barbara M.; Abrell, Leif; Crews, Phillip

doi:10.1016/s0040-4020(01)80012-0

Cited by 97 publications

(122 citation statements)

References 43 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…(Fig. 1) Compounds 2-10 were identified as smenospongorine, 6,7) 5-epi-smenospongine, 6,8) smenospongine, 6,7,9) 5-epi-smenospongidine, 6) smenospongidine, 7) 5-epi-ilimaquinone, 6) 13 C-NMR signals due to the decalin part and the quinone part in 1 were closely similar to those of 5-epi-smenospongidine (5) 6) and smenospongorine (2), 7) respectively. Then, it is presumed that compound 1 is a hybrid of 5-epismenospongidine (5) and smenospongorine (2).…”

Section: Resultsmentioning

confidence: 90%

Sesquiterpene Aminoquinones, from a Marine Sponge, Induce Erythroid Differentiation in Human Chronic Myelogenous Leukemia, K562 Cells

Aoki

Kong

Matsui

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Despite the various cancer therapeutic methods such as chemotherapy, which are being carried out clinically, cancer remains to be a serious and, in most cases, fatal disease. Chemotherapeutic drugs affect not only tumor cells but also proliferative normal cells such as bone marrow cells and result in serious side effects. To solve this problem, several other alternative therapeutic methods are being developed. The differentiation-induction therapy, in which tumor cells are differentiated to normal cells, seems to be one promising therapy. As a good example of differentiation inducer, ATRA (all-trans-retinoic acid) has shown superior therapeutic effect on acute promyelocytic leukemia (APL), which is unresponsive to conventional chemotherapeutic drugs.1) However, several kinds of leukemia such as human chronic myelogenous leukemia (CML) are unresponsive to ATRA. So, development of new differentiation inducers has been required.As a part of our exploratory research of bioactive substances from marine organisms, we have been searching for new differentiation inducers to tumor cells and have found several inducers to ATRA-nonresponsive CML (K562 cells) or murine neuroblastoma (Neuro 2A cells) from marine sponges.2-4) Recently, we have isolated from a marine sponge 5) a sesquiterpene aminoquinone, smenospongine (4), which induces differentiation of K562 cells into erythroblasts. Study on its action mechanism showed that smenospongine induced arrest of the cell cycle at the G1 phase and increased expression of p21 protein, a Cip1/Waf1 cdk (cyclin dependent kinase) inhibitor.5) This interesting action of smenospongine led us to continue further study, and we isolated ten sesquiterpene quinones/phenol analogues from the same marine sponge, including a new compound named 5-epi-smenospongorine (1). In this paper, the structure-activity relationship of these sesquiterpene quinones is discussed. Results and DiscussionChemical Structures of 5-epi-Smenospongorine (1) and the Analogues The nine sesquiterpene quinone/phenols (2-10) together with a new compound named 5-epismenospongorine (1) were isolated from the marine sponge Dactylospongia elegans. (Fig. 1) Compounds 2-10 were identified as smenospongorine, 6,7) 5-epi-smenospongine, 6,8) smenospongine, 6,7,9) C-NMR signals due to the decalin part and the quinone part in 1 were closely similar to those of 5-epi-smenospongidine (5) 6) and smenospongorine (2), 7) respectively. Then, it is presumed that compound 1 is a hybrid of 5-epismenospongidine (5) and smenospongorine (2).8) This presumption that compound 1 is an epimer at the C-5 position of smenospongorine (2) was further confirmed by nuclear overhauser effect spectroscopy (NOESY) analysis of both compounds 1 and 2. Thus, the correlations between H-12 and H-10 for compound 1 and between H-12 and H-14 for compound 2 were found. Based on these evidences, compound 1 was determined as 5-epi-smenospongorine as shown in Fig. 1. A new sesquiterpene aminoquinone, 5-epi-smenospongorine, together with nine known sesquiterpene quino...

show abstract

Section: Resultsmentioning

confidence: 90%

Sesquiterpene Aminoquinones, from a Marine Sponge, Induce Erythroid Differentiation in Human Chronic Myelogenous Leukemia, K562 Cells

Aoki

Kong

Matsui

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…A representative example is compound 32 (Figure 8). Several of the obtained compounds showed IC 50 values under the micromolar level, and an important selectivity toward renal cancer lines, identifying these compounds as a very promising group of antineoplastics. The structure of the compound 32 could be partially superimposed on the crystal structure of avarol, which allows speculation that these molecules might interact at the same site and in a similar molecular orientation [55].…”

Section: Figurementioning

confidence: 98%

“…[46,47], which also shows a potent antituberculosis activity [48]). Among those are also the ones with a 4,9-friedo-rearranged skeleton, such as ilimaquinone (3) [49], and a related amino derivative 15 from the sponge Dactylospongia elegans [50], the nakijiquinones 5 [11] and especially avarone (2) and avarol (1), with strong ED 50 activities of 0.62 µM and 0.93 µM, respectively, for mouse lymphoma cells [51,52]. Also, strong activity was evidenced for several hydroxy and acetoxy derivatives 16-18 of avarol and avarone, isolated from the marine sponge Dysidea cinerea [53] (Figure 4).…”

Section: Biological Effects I) Antitumor Activitymentioning

confidence: 99%

“…Metachromins A (22), and B (23), hypochromin A diacetate (24) and metachromin B monoacetate (25) ( Figure 5) exhibit potent cytotoxicities against human colon and nasopharyngeal tumor cells with IC 50 values of less than 1 µM [59]. Another example is the moderately cytotoxic naphthoquinone sesquiterpene neomarinone (26) produced by a marine actinomycete [60].…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Reactivity and Biological Activity of the Marine Sesquiterpene Hydroquinone Avarol and Related Compounds from Sponges of the Order Dictyoceratida

Sladić

Gašić

2006

Molecules

View full text Add to dashboard Cite

A review of results of bioactivity and reactivity examinations of marine sesquiterpene (hydro)quinones is presented. The article is focused mostly on friedorearranged drimane structural types, isolated from sponges of the order Dictyoceratida. Examples of structural correlations are outlined. Available results on the mechanism of redox processes and examinations of chemo-and regioselectivity in addition reactions are presented and, where possible, analyzed in relation to established bioactivities. Most of the bioactivity examinations are concerned with antitumor activities and the mechanism thereof, such as DNA damage, arylation of nucleophiles, tubulin assembly inhibition, protein kinase inhibition, inhibition of the arachidonic cascade, etc. Perspectives on marine drug development are discussed with respect to biotechnological methods and synthesis. Examples of the recognition of validated core structures and synthesis of structurally simplified compounds retaining modes of activity are analyzed.

show abstract

“…However, absolute configurations of all compounds 3-6, particularly absolute configuration of chiral centers at the cyclopentenone moiety (C-16, C-17), have not been confirmed. 12,14) Therefore, absolute configurations at C-16 and C-17 of the compounds 3-6 were attempted to determine by combination of experimental and theoretical calculation circular dichroism (CD) spectra (Supplementary materials). Four possible enantiomers (16R,17S), (16S,17R), (16R,17R) and (16S,17S) were subjected to time dependent density functional theory (TDDFT) calculations at the B3LYP/6-31G(d,p) basic set with acetonitril as a polarizable continuum model (PCM).…”

Section: Resultsmentioning

confidence: 99%

Naphtoquinones and Sesquiterpene Cyclopentenones from the Sponge <i>Smenospongia cerebriformis</i> with Their Cytotoxic Activity

Huyen

Hằng

Nhiệm

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Two new naphtoquinones (smenoceronesMarine sponges have produced a huge variety of secondary metabolites in which approximate 300 new structures were reported annually in the past decade.1-3) Sponge derived compounds are not only displayed unique chemical structures but also interesting biological properties and made sponges become a potent source of lead compounds for new drug discovery.1,4) Sponge genus Smenospongia (order Dictyoceratida, family Thorectidae) has been found comprising 19 species. Especially, 12 new species were described in recent three years. 5)Smenospongia sponges were mentioned to produce large number of brominated indole alkaloids, 6) popyketides, 7) sesterterpenes, 8) and unique structure of merosesquiterpenes 9,10) such as sesquiterpene quinone, sesquiterpene phenol, and sesquiterpene cyclopentenone. In this paper, we report the isolation, structure determination, and cytotoxic effect towards lung carcinoma (LU-1), hepatocellular carcinoma (HepG-2), promyelocytic leukemia (HL-60), breast carcinoma (MCF-7), and melanoma (SK-Mel-2) human cancer cells of two new naphtoquinones and four known sesquiterpene cyclopentenones from the sponge S. cerebriformis living at the Eastern Sea of Vietnam.

show abstract

The structures and stereochemistry of cytotoxic sesquiterpene quinones from dactylospongia elegans

Cited by 97 publications

References 43 publications

Sesquiterpene Aminoquinones, from a Marine Sponge, Induce Erythroid Differentiation in Human Chronic Myelogenous Leukemia, K562 Cells

Sesquiterpene Aminoquinones, from a Marine Sponge, Induce Erythroid Differentiation in Human Chronic Myelogenous Leukemia, K562 Cells

Reactivity and Biological Activity of the Marine Sesquiterpene Hydroquinone Avarol and Related Compounds from Sponges of the Order Dictyoceratida

Naphtoquinones and Sesquiterpene Cyclopentenones from the Sponge <i>Smenospongia cerebriformis</i> with Their Cytotoxic Activity

Contact Info

Product

Resources

About