Synthesis of Novel Laurenditerpenol Analogues and their Evaluation as HIF-1 Activation Inhibitors

Athinaios, Nikolaos; Kazantzis, Athanasios; Putzker, Kerstin; Lewis, Joe; Pitsinos, Emmanuel N.

doi:10.2174/157017809788489891

Cited by 6 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rearranged obtusane laurenditerpenol (613) exhibited potent inhibition of HIF-1-mediated hypoxic signaling in breast tumor cells [521]. Two analogues featuring the 7-oxabicyclo[2.2.1]heptane ring system present in the natural product were prepared and their weak inhibition of HIF-1 activation indicated the importance of the cyclohexenol part of laurenditerpenol (613) [862]. The diterpenes prevezols B-E (617-620) were tested for their cytotoxicity against five human tumor cell lines (MCF-7, PC-3, HeLa, A-431, and K-562) and prevezols B (617) and C (618) were found to be the most potent, while prevezol E (620) was inactive [528].…”

Section: Cytotoxic Activitymentioning

confidence: 99%

See 1 more Smart Citation

The Laurencia Paradox: An Endless Source of Chemodiversity

Harizani

Iοannou

Roussis

2016

Progress in the Chemistry of Organic Natural Products

View full text Add to dashboard Cite

Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth's surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.Red algae of the genus Laurencia are accepted unanimously as one of the richest sources of new secondary metabolites. Their cosmopolitan distribution, along with the chemical variation influenced to a significant degree by environmental and genetic factors, have resulted in an endless parade of metabolites, often featuring multiple halogenation sites.The present contribution, covering the literature until August 2015, offers a comprehensive view of the chemical wealth and the taxonomic problems currently impeding chemical and biological investigations of the genus Laurencia. Since mollusks feeding on Laurencia are, in many cases, bioaccumulating, and utilize algal metabolites as chemical weaponry against natural enemies, metabolites of postulated dietary origin of sea hares that feed on Laurencia species are also included in the present review. Altogether, 1047 secondary metabolites, often featuring new carbocyclic skeletons, have been included.The chapter addresses: (1) the "Laurencia complex", the botanical description and the growth and population dynamics of the genus, as well as its chemical diversity and ecological relations; (2) the secondary metabolites, which are organized according to their chemical structures and are classified into sesquiterpenes, diterpenes, triterpenes, acetogenins, indoles, aromatic compounds, steroids, and miscellaneous compounds, as well as their sources of isolation which are depicted in tabulated form, and (3) the biological activity organized according to the biological target and the ecological functions of Laurencia metabolites.

show abstract

Section: Cytotoxic Activitymentioning

confidence: 99%

“…The epoxy derivative 82 of okamurene E debromoallolaurinterol acetate (150), and allolaurinterol acetate (152) exhibited potent activity in the brine shrimp assay, 41, 424, and epilaurallene (ent-854) showed weak activity, whereas laurene (148) and desepilaurallene (862) were found inactive [152].…”

Section: Brine Shrimp Toxicitymentioning

confidence: 99%

The Laurencia Paradox: An Endless Source of Chemodiversity

Harizani

Iοannou

Roussis

2016

Progress in the Chemistry of Organic Natural Products

View full text Add to dashboard Cite

show abstract

Section: Cytotoxic Activitymentioning

confidence: 99%

Progress in the Chemistry of Organic Natural Products 102

Kinghorn¹,

Falk²,

Gibbons³

et al. 2016

Progress in the Chemistry of Organic Natural Products

View full text Add to dashboard Cite

show abstract

“…This effective compound latrunculin A is a marine-derived macrolide from the Red Sea sponge Negombata magnifica. The terpene-derived furanolipid furospongolide, isolated from an active lipid extract of a Saipan collection of the marine sponge Lendenfeldia sp., blocked Apigenin AKT (not so clear) [127] Vitexin unknown [128] Kaempferol unkown [126] Polyphenon-B unknown [175] NSC643735, NSC134754 unknown [176] Laurenditerpenol and analogues unknown [177,178] Latrunculin A unknown [179] Aplidin (plitidepsin, APLD) unknown [180] Strongylophorines HIF-1 transcriptional pathway [181] Sodwanone and yardenone triterpenes unkown [182] Bakuchiols unkown [183,184] the induction of the downstream HIF-1 target secreted VEGF and was shown to inhibit HIF-1 activation (IC 50 2.9IM, T47D breast tumor cells) primarily by suppressing tumor cell respiration via the blockade of NADH-ubiquinone oxidoreductase-mediated mitochondrial electron transfer [84]. Strongylophorine-26, which belongs to the meroditerpenoid family, was previously found to have potent anti-invasive activity in MDA-MB-231 breast cancer cells [185].…”

Section: Marine Natural Productsmentioning

confidence: 99%

Cancer Therapeutic Agents Targeting Hypoxia-Inducible Factor-1

Wang¹,

Zhou

2011

CMC

View full text Add to dashboard Cite

The discovery of hypoxia-inducible factor-1 has led to a rapidly increasing understanding of the molecular mechanism of tumor hypoxia in the past two decades. Today it is generally accepted that HIF-1 plays a pivotal role in the cellular response to tumor hypoxia which represents a major obstacle to the success of radiotherapy and chemotherapy. Meanwhile, many details involved in the expression, accumulation and transactivation of HIF-1 have been well elucidated. Targeting HIF-1 has become a novel and efficient strategy for cancer therapy and a number of agents have been developed aiming to suppress HIF-1. This review will concisely introduce the general knowledge on the molecular biology of HIF-1 and possible targets along the HIF-1 pathway. Moreover, a number of compounds reported with anti-HIF-1 activity are included and mainly classified as direct and indirect inhibitors based on their different modes of action. While direct HIF-1 inhibitors prevent HIF-1 from transactivation, DNA binding and subsequently initiating transcriptional activity, indirect HIF-1 inhibitors generally block the transcription or translation of HIF-1α or promote the degradation of HIF-1α protein. According to different structural features, direct HIF-1 inhibitors are divided into several groups: polyamides, quinols and naphthoquinone spiroketal analogues, shikonin derivatives, epidithiodiketopiperazines, and two representative drugs: echinomycin and bortezomib. In the same way, indirect inhibitors comprise the following classes: polyphenols, benzoazaheterocycles, rapamycins, camptothecins, geldanamycins, (aryloxyacetylamino)benzoic acid analogues, 2-methoxyestradiol and analogues, hydroxamic acid compounds and others. The rest with mechanism still not so clear would also be listed and introduced, with an emphasis on the marinederived natural products. The in vitro and/or in vivo activities of these compounds and their mechanisms of HIF-1 inhibition would be discussed and the SARs of unique structural types of HIF-1 inhibitors will be briefly concluded.

show abstract

Synthesis of Novel Laurenditerpenol Analogues and their Evaluation as HIF-1 Activation Inhibitors

Cited by 6 publications

References 0 publications

The Laurencia Paradox: An Endless Source of Chemodiversity

The Laurencia Paradox: An Endless Source of Chemodiversity

Progress in the Chemistry of Organic Natural Products 102

Cancer Therapeutic Agents Targeting Hypoxia-Inducible Factor-1

Contact Info

Product

Resources

About