Concise synthesis and structure–activity relationship of furospinosulin-1, a hypoxia-selective growth inhibitor from marine sponge

Kotoku, Naoyuki; Fujioka, Shinichi; Nakata, Chiaki; Yamada, Masaki; Sumii, Yuji; Kawachi, Takashi; Arai, Masayoshi; Kobayashi, Mariko

doi:10.1016/j.tet.2011.05.009

Cited by 24 publications

(31 citation statements)

References 13 publications

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“…It was also shown to suppress the transcription of the insulin-like growth factor-2 (IGF-2) gene [59]. Its C4-desmethyl analogue also showed significant selective activity under hypoxic conditions and antitumor activity in vivo after an oral administration [60]. …”

Section: Introductionmentioning

confidence: 99%

Sesterterpenoids with Anticancer Activity

Evidente¹,

Kornienko²,

Lefranc³

et al. 2015

CMC

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Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review.

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Section: Introductionmentioning

confidence: 99%

Sesterterpenoids with Anticancer Activity

Evidente¹,

Kornienko²,

Lefranc³

et al. 2015

CMC

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“…Further studies revealed that 1 abolished complex formation between an oligonucleotide probe containing the consensus sequence of the Sp1 transcription factor and nuclear proteins, under hypoxic conditions . In addition, we achieved a concise and practical synthesis of 1 and its analogues . The structure–activity relationship of the analogues revealed that the entire chemical structure was important for hypoxia‐selective growth inhibition, and that the binding protein(s) through which it produces this effect might require its entire structure.…”

Section: Introductionmentioning

confidence: 93%

Furospinosulin‐1, Marine Spongean Furanosesterterpene, Suppresses the Growth of Hypoxia‐Adapted Cancer Cells by Binding to Transcriptional Regulators p54^nrb and LEDGF/p75

et al. 2015

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Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. Cancer research has therefore focused on the identification of molecules responsible for hypoxia adaptation in cancer cells, as well as the development of new compounds with action against hypoxia-adapted cancer cells. The marine natural product furospinosulin-1 (1) has displayed hypoxia-selective growth inhibition against cultured cancer cells, and has shown in vivo anti-tumor activity, although its precise mode of action and molecular targets remain unclear. In this study, we found that 1 is selectively effective against hypoxic regions of tumors, and that it directly binds to the transcriptional regulators p54(nrb) and LEDGF/p75, which have not been previously identified as mediators of hypoxia adaptation in cancer cells.

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“…• In vivo anti-tumor effect with oral administration desmethyl analogue (14) heterocyclic part side chain part SAR Fig. 2 Chemical structures of furospinosulin-1 ( 13 ), desmethyl analogue ( 14 ), and synthetic strategy for structure-activity relationship study protein expression of IGF-2 induced under hypoxic conditions, and the hypoxiainduced autophosphorylations of IGF-1 receptor and insulin receptor proteins, which correspond to the receptors of IGF-2 protein, were also suppressed by treatment with compound 13 [ 13 ] .…”

Section: Action Mechanism Of Furospinosulin-1mentioning

confidence: 99%

“…As there was no information about the structural requirement for the hypoxia-selective growth inhibitory activity of compound 13 , we decided to examine its structure-activity relationship through synthesis and biological evaluation of some structurally modi fi ed analogues [ 14 ] . First, we studied total synthesis of furospinosulin-1 ( 13 ) to supply a suf fi cient amount of compound 13 and to establish a practical method to prepare various analogues.…”

Section: Syntheses Of Furospinosulin-1 Analoguesmentioning

confidence: 99%