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Adenosine Monophosphate-Activated Protein Kinase or AMPK is a highly-conserved master-regulator of numerous cellular processes, including: Maintaining cellular-energy homeostasis, modulation of cytoskeletal-dynamics, directing cell growth-rates and influencing cell-death pathways. AMPK has recently emerged as a promising molecular target in cancer therapy. In fact, AMPK deficiencies have been shown to enhance cell growth and proliferation, which is consistent with enhancement of tumorigenesis by AMPK-loss. Conversely, activation of AMPK is associated with tumor growth suppression through inhibition of the Mammalian Target of Rapamycin Complex-1 (mTORC1) or the mTOR signal pathway. The scientific communities' recognition that AMPK-activating compounds possess an anti-neoplastic effect has contributed to a rush of discoveries and developments in AMPK-activating compounds, as potential anticancer-drugs. One such example is the class of compounds known as Biguanides, which include: Metformin and Phenformin. The current review will showcase natural compounds and their derivatives that activate the AMPK-complex and signaling pathway. In addition, the biology and history of AMPK-signaling and AMPK-activating compounds will be overviewed; their anticancer-roles and mechanisms-of-actions will be discussed, and potential strategies for the development of novel, selective AMPK-activators with enhanced efficacy and reduced toxicity will be proposed.

Park S, Park CS, L. S. J. C. C. Y. A. S. Y. E. A. K. G. S. J. J. S. A. E. - A. A. M. E. - B. H. A. B. Y., "Development and validation of a high-performance liquid chromatography-tandem mass spectrometric method for simultaneous determination of bupropion, quetiapine and escitalopram in human plasma.", Biomedical chromatography, vol. 7, issue 4, pp. 369-384, 2013. Abstract

In the present study, an effective high performance liquid chromatography-tandem mass spectrometric (HPLC/MS/MS) method was developed and validated to simultaneously determine bupropion (BUP), quetiapine (QUE) and escitalopram (ESC) in human plasma using carbidopa as the internal standard. Chromatographic separation was achieved on a Waters Sun Fire C18 column using reversed-phase chromatography. The MS/MS experiment was performed in positive ion multiple reaction monitoring mode to produce product ions of m/z 240.3 → 184.2 for BUP, 384.2 → 253.1 for QUE, 325.3 → 109.3 for ESC and 227.2 → 181.2 for the internal standard. The method showed good linearity (R(2)  ≥ 0.997), precision (relative standard deviation ≤7.5%), satisfactory intra- and interday accuracy (88.4-113.0%) and acceptable extraction recovery (87.2-115.0%), matrix effect (84.5.5-108.7%) and stability (92.3-103.5%). The method was successfully applied to determine the concentrations of BUP, QUE and ESC in human plasma samples. Copyright © 2014 John Wiley & Sons, Ltd.

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