Covering: 2009 to 2022The Stemona alkaloids, which are found in plant species from the family Stemonaceae, represent a tremendously large and structurally-diverse family of natural products. This review presents and discusses a selection of case studies, grouped by alkaloid class, that showcase the key strategies and overall progress that has been made in the synthesis of Stemona alkaloids and related compounds since 2009. Structural reassignments that have been reported over this period are also identified where necessary.

10.1039/d2np00058j

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Citations (8)

Heterocyclic cyclohexanone monocarbonyl analogs of curcumin can inhibit the activity of ATP-binding cassette transporters in cancer multidrug resistance

Biochemical Pharmacology (2014)

Jezrael L. Revalde Yan Li Bill C. Hawkins Rhonda J. Rosengren James W. Paxton

Abcg2

Efflux

P-glycoprotein

Multidrug Resistance-Associated Proteins

10.1016/j.bcp.2014.12.012

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Citations (33)

CCDC 2100345: Experimental Crystal Structure Determination

The Cambridge Structural Database (2021)

Jackson S. Henneveld Selena C. L. Gilmer Nigel T. Lucas Bill C. Hawkins

10.5517/ccdc.csd.cc28hl2g

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Sprioleucettadine Ashton

Zenodo (CERN European Organization for Nuclear Research) (2022)

John C. Ashton Ben Watts Abigail R. Bland Ben Watts Michael Bardart

10.5281/zenodo.7178632

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Synthetic Strategies to Access Heteroatomic Spirocentres Embedded in Natural Products

Synthesis (2021)

Michael P. Badart Bill C. Hawkins

Abstract The spirocyclic motif is abundant in natural products and provides an ideal three-dimensional template to interact with biological targets. With significant attention historically expended on the synthesis of flat-heterocyclic compound libraries, methods to access the less-explored three-dimensional medicinal-chemical space will continue to increase in demand. Herein, we highlight by reaction class the common strategies used to construct the spirocyclic centres embedded in a series of well-studied natural products. 1 Introduction 2 Cycloadditions 3 Palladium-Catalysed Coupling Reactions 4 Conjugate Additions 5 Imines, Aminals, and Hemiaminal Ethers 6 Mannich-Type Reactions 7 Oxidative Dearomatisation 8 Alkylation 9 Organometallic Additions 10 Conclusions

Hemiaminal

Conjugate

Chemical space

10.1055/a-1379-2312

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Citations (17)

Bioinstrumentation

Biomedical engineering (2018)

Bill C. Hawkins

The second edition of this popular introductory undergraduate textbook uses examples, applications, and profiles of biomedical engineers to show students the relevance of the theory and how it can be used to solve real problems in human medicine. The essential molecular biology, cellular biology, and human physiology background is included for students to understand the context in which biomedical engineers work. Updates throughout highlight important advances made over recent years, including iPS cells, microRNA, nanomedicine, imaging technology, biosensors, and drug delivery systems, giving students a modern description of the various subfields of biomedical engineering. Over two hundred quantitative and qualitative exercises, many new to this edition, help consolidate learning, whilst a solutions manual, password-protected for instructors, is available online. Finally, students can enjoy an expanded set of leader profiles in biomedical engineering within the book, showcasing the broad range of career paths open to students who make biomedical engineering their calling.

Relevance

10.1017/cbo9781139583831.012

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Anticancer potential of novel curcumin analogs towards castrate-resistant prostate cancer

International Journal of Oncology (2017)

Shuli Chen Mhairi Nimick Andrew G. Cridge Bill C. Hawkins Rhonda J. Rosengren

Prostate cancer is initially sensitive to hormone therapy; however, over time the majority of patients progress to a hormone-insensitive form classified as castration-resistant prostate cancer (CRPC). CRPC is highly metastatic and patients have a poor prognosis. Thus, new drugs for the treatment of this disease are required. In this study, we therefore examined the cytotoxic effects and anticancer mechanism(s) of action of second generation curcumin analogs towards CRPC cells. For this purpose, PC3 and DU145 cells were treated with a series of curcumin analogs at 0-10 µM for 72 h and cytotoxicity was determined by the sulforhodamine B (SRB) assay. Two compounds, 1-isopropyl-3,5-bis(pyridin-3-ylmethylene)-4-piperidone (RL118) and 1-methyl-3,5-[(6-methoxynaphthalen-2-yl)methylene]-4-piperidone (RL121), were found to have the most potent cytotoxic effect with EC50 values of 0.50 and 0.58 µM in the PC3 cells and EC50 values of 0.76 and 0.69 µM in the DU145 cells, respectively. Thus, further experiments were performed focusing on these two compounds. Flow cytometry was performed to determine their effects on the cell cycle and apoptosis. Both analogs increased the number of cells in the G2/M phase of the cell cycle and induced apoptosis. Specifically, in the PC3 cells, RL121 increased the number of cells in the G2/M phase by 86% compared to the control, while RL118 increased the number of cells in the G2/M phase by 42% compared to the control after 24 h. Moreover, both RL118 and RL121 induced the apoptosis of both cell lines. In the DU145 cells, a 38-fold increase in the number of apoptotic cells was elicited by RL118 and a 78-fold increase by RL121 compared to the control. Furthermore, the effects of both analogs on the expression of key proteins involved in cell proliferation were also determined by western blot analysis. The results revealed that both analogs inhibited the expression of nuclear factor (NF)-κB (p65/RelA), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), p-4E-BP1, mammalian target of rapamycin (mTOR), p-mTOR, AKT and p-AKT. Thus, the findings of this study provide evidence that RL118 and RL121 have potent anticancer activity against CPRC cells, and both analogs warrant further investigation in vivo.

DU145

10.3892/ijo.2017.4207

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Citations (25)