Isolation, biological activity, biosynthesis and synthetic studies towards the rubromycin family of natural products

Atkinson, Darcy J.; Brimble, Margaret A.

doi:10.1039/c4np00153b

Cited by 56 publications

(35 citation statements)

References 70 publications

(159 reference statements)

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“…The isolated enantiomers did not evidently epimerize under the acidic separation conditions (Supporting Information) nor was any significant change in EC 50 value observed for either 1 ‐ ent1 or 1 ‐ ent2 in the same FP assay over a 24 h period (Supporting Information) as evidence of the stability of these compounds under the aqueous assay conditions. Our findings are consistent with those from studies on similar benzannulated spiroketals and the fact that analogous natural products are isolated as single enantiomers …”

Section: Figuresupporting

confidence: 92%

Designed Spiroketal Protein Modulation

et al. 2017

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Spiroketals are structural motifs found in many biologically active natural products,w hich has stimulated considerable efforts towardtheir synthesis and interest in their use as drug lead compounds.D espite this,t he use of spiroketals,a nd especially bisbenzanulated spiroketals,i n astructure-based drug discovery setting has not been convincingly demonstrated. Herein, we report the rational design of ab isbenzannulated spiroketal that potently binds to the retinoid Xr eceptor (RXR) therebyi nducing partial coactivator recruitment. We solved the crystal structure of the spiroketal-hRXRa-TIF2 ternary complex, and identified ac anonical allosteric mechanism as ap ossible explanation for the partial agonist behavior of our spiroketal. Our cocrystal structure,t he first of ad esigned spiroketal-protein complex, suggests that spiroketals can be designed to selectively target other nuclear receptor subtypes.

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Section: Figuresupporting

confidence: 92%

Designed Spiroketal Protein Modulation

et al. 2017

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“…They possess a naphthoquinone ring and an isocoumarin ring connected through a 5,6-spiroketal system. 1 …”

Section: Introductionmentioning

confidence: 99%

Absolute configurations of griseorhodins A and C

Ortega

Batista

Melo

et al. 2017

Tetrahedron Letters

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The known antibiotic and cytotoxic compounds griseorhodin A (1) and griseorhodin C (2) were produced in solid culture by Streptomyces puniceus AB10, which was isolated from the leaf-cutter ant Acromyrmex rugosus rugosus. Their absolute configurations were unambiguously established as 6S,6aR,7S,8S and 6R,6aR,7S,8R, respectively, using vibrational circular dichroism (VCD) and density functional theory (DFT) calculations.

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“…Examples include compounds from microbial sources such as TLM, a macrocyclic alkaloid isolated from the bacteria Streptomyces anulatus, chrolactomycin, a compound found in Streptomyces sp. 569N-3 and rubromycins, a group of molecules with an uncommon 5,6-spiroketal core, extracted from various catinomycete species [58][59][60]. TLM has been demonstrated to be a very potent and selective telomerase inhibitor due to its remarkable selectivity for the G-quadruplex telomeric structures [61].…”

Section: Telomerase Inhibitionmentioning

confidence: 99%

Targeting Multiple Myeloma Cancer Stem Cells with Natural Products – Lessons from Other Hematological Malignancies

2017

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Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. Multiple myeloma is the second most frequently diagnosed hematological malignancy, predominantly affecting the elderly. Despite recent advances in the development of novel therapies, multiple myeloma remains an incurable malignancy where the majority of patients relapse, develop resistance, and eventually die from the disease. This has been attributed to the fact that conventional therapy currently in use targets mainly the bulk of tumor cells, but not the tumor-initiating cancer stem cells. Cancer stem cells are a highly resistant subpopulation of cells believed to be responsible for the initiation, progression, metastasis, and relapse of cancer. Enormous efforts have been invested in the characterization of cancer stem cells. These efforts led to the characterization of key cellular signaling pathways responsible for conferring stem cell characteristics including self-renewal, differentiation, migratory, survival, and intracellular detoxification capabilities. Targeting these protective mechanisms offers a valuable strategy that may help combat a major driving force behind cancers. The use of natural products offers a promising therapeutic approach for targeting cancer stem cells. In this review, recent advances achieved in the characterization of cancer stem cells derived from hematological malignancies, with a particular focus on multiple myeloma, are discussed and major natural products that target cancer stem cells are presented. As natural products remain an essential source of novel chemical structures and medicinal leads, the exploitation of this immense reservoir is used to draw lessons in targeting multiple myeloma-cancer stem cells.

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Isolation, biological activity, biosynthesis and synthetic studies towards the rubromycin family of natural products

Cited by 56 publications

References 70 publications

Designed Spiroketal Protein Modulation

Designed Spiroketal Protein Modulation

Absolute configurations of griseorhodins A and C

Targeting Multiple Myeloma Cancer Stem Cells with Natural Products – Lessons from Other Hematological Malignancies

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