scholarly journals New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889)

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 97
Author(s):  
Shamsunnahar Khushi ◽  
Angela A. Salim ◽  
Ahmed H. Elbanna ◽  
Laizuman Nahar ◽  
Robert J. Capon

Thorectandra choanoides (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (1), with the GNPS cluster revealing a halo of related alkaloids 1a–1n. In considering biosynthetic origins, we propose that Thorectandrachoanoides (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (2), 6-bromoaplysinopsin (3), aplysinopsin (4), and 1′,8-dihydroaplysinopsin (10), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-like (IDO) enzyme to 1a–1n. Where the 1′,8-dihydroalkaloids 2 and 10 are fully transformed to stable ring-opened thorectandrins 1 and 1a–1b, and 1h–1j, respectively, the conjugated precursors 3 and 4 are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts 1c–1g, and 1k–1n, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme.

2010 ◽  
Vol 63 (6) ◽  
pp. 873 ◽  
Author(s):  
Chongsheng Peng ◽  
G. M. Kamal B. Gunaherath ◽  
Andrew M. Piggott ◽  
Zeinab Khalil ◽  
Melissa Conte ◽  
...  

Chemical fractionation of a southern Australian marine sponge, Trachycladus laevispirulifer, yielded 9-(5′-deoxy-5′-thio-β-d-xylofuranosyl)adenine disulfide as the first recorded natural occurrence of a nucleoside disulfide, and only the second of a xylo-nucleoside. Structure elucidation of the disulfide was achieved by detailed spectroscopic analysis and comparison to synthetic model compounds. The antibacterial, antifungal, and anticancer properties of the disulfide are documented and the literature surrounding natural and synthetic thionucleosides is reviewed.


2014 ◽  
pp. 15-20
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Trung Nghia Van ◽  
Viet Nhan Nguyen ◽  
Phan Tuong Quynh Le ◽  
...  

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.


Wear ◽  
2008 ◽  
Vol 265 (9-10) ◽  
pp. 1396-1401 ◽  
Author(s):  
Yasutomo Sone ◽  
Junichi Suzumura ◽  
Takumi Ban ◽  
Fusayoshi Aoki ◽  
Makoto Ishida

2016 ◽  
Vol 88 (5) ◽  
pp. 2792-2798 ◽  
Author(s):  
Christopher B. Raub ◽  
Chen-Chung Lee ◽  
Darryl Shibata ◽  
Clive Taylor ◽  
Emil Kartalov

Author(s):  
Alex E. Roher ◽  
Kenneth C. Palmer ◽  
John Capodilupo ◽  
Arun R. Wakade ◽  
Melvyn J. Ball

ABSTRACT:Purification of amyloid plaque core proteins (APCP) from Alzheimer's disease brains to complete homogeneity and in high yield permitted its chemical fractionation and characterization of its components. APCP is mainly made of β-amyloid (βA) and an assortment of glycoproteins (accounting for 20%) rich in carbohydrates compatible with N-and O-linked saccharides. When added to tissue culture of sympathetic and sensory neurons APCP and βA inhibited neuritic sprouting, a reversible phenomenon at low doses. Higher concentrations of both substances kill the neurons in culture. APCP is significantly more toxic than βA, suggesting the minor components may play an important role in increasing the toxicity of βA. If the observed toxic effects of APCP in situ are occurring in vivo during the course of AD, then the accumulation of these extracellular proteins could be largely responsible for some of the neuronal death observed in this neuropathology.


2017 ◽  
Vol 983 ◽  
pp. 54-66 ◽  
Author(s):  
Amauri Antonio Menegário ◽  
Lauren N. Marques Yabuki ◽  
Karen S. Luko ◽  
Paul N. Williams ◽  
Daniel M. Blackburn

2014 ◽  
Vol 9 (4) ◽  
pp. 1934578X1400900
Author(s):  
Bin Wang ◽  
Yaocai Lin ◽  
Yinning Chen ◽  
Riming Huang

Investigation of the marine sponge Haliclona sp. led to the isolation of two new thyminenol derivatives, named cis-thyminenol (1) and trans-thyminenol (2). The structures of the new isolates were elucidated on the basis of extensive spectroscopic analysis.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Gedmante Radziuviene ◽  
Allan Rasmusson ◽  
Renaldas Augulis ◽  
Daiva Lesciute-Krilaviciene ◽  
Aida Laurinaviciene ◽  
...  

Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases. We investigated statistically derived indicators of HER2 heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio; however, it collected more amplified cells in some cases below the lower limit of GH definition by manual procedure. Indicators for amplification, polysomy, and bimodality were extracted by factor analysis and allowed clustering of the tumors into amplified, nonamplified, and equivocal/polysomy categories. The bimodality indicator provided independent cell diversity characteristics for all clusters. Tumors classified as bimodal only partially coincided with the conventional GH heterogeneity category. We conclude that automated high-capacity nonselective tumor cell assay can generate evidence-based HER2 intratumor heterogeneity indicators to refine GH definitions.


2016 ◽  
Vol 3 ◽  
Author(s):  
Adi Lavy ◽  
Ray Keren ◽  
Gitai Yahel ◽  
Micha Ilan

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