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Full-Text Articles in Physical Sciences and Mathematics

Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady Aug 2020

Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady

Physiology Faculty Publications

Techniques available for micro- and nano-scale mechanical characterization have exploded in the last few decades. From further development of the scanning and transmission electron microscope, to the invention of atomic force microscopy, and advances in fluorescent imaging, there have been substantial gains in technologies that enable the study of small materials. Conpokal is a portmanteau that combines confocal microscopy with atomic force microscopy (AFM), where a probe "pokes" the surface. Although each technique is extremely effective for the qualitative and/or quantitative image collection on their own, Conpokal provides the capability to test with blended fluorescence imaging and mechanical characterization. Designed …


Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova Feb 2018

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …


Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams From An Eastern Kentucky Abandoned Coal Mine Microbe, Xiachang Wang, Yinan Zhang, Larissa V. Ponomareva, Qingchao Qiu, Ryan M. Woodcock, Sherif I. Elshahawi, Xiabin Chen, Ziyuan Zhou, Bruce E. Hatcher, James C. Hower, Chang-Guo Zhan, Sean Parkin, Madan K. Kharel, S. Randal Voss, Khaled A. Shaaban, Jon S. Thorson Mar 2017

Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams From An Eastern Kentucky Abandoned Coal Mine Microbe, Xiachang Wang, Yinan Zhang, Larissa V. Ponomareva, Qingchao Qiu, Ryan M. Woodcock, Sherif I. Elshahawi, Xiabin Chen, Ziyuan Zhou, Bruce E. Hatcher, James C. Hower, Chang-Guo Zhan, Sean Parkin, Madan K. Kharel, S. Randal Voss, Khaled A. Shaaban, Jon S. Thorson

Center for Pharmaceutical Research and Innovation Faculty Publications

Four cyclopentenone‐containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD‐23‐14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19‐hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α …