3 research outputs found
Total Synthesis of Nominal Lyngbouilloside Aglycon
The first enantioselective total synthesis of the originally assigned structure of lyngbouilloside aglycon has been achieved using a particularly flexible route featuring an acylketene macrolactonization of a tertiary methyl carbinol as the key step. Comparison of the C13 chemical shifts of our synthetic aglycon with the ones pertaining to natural lyngbouilloside and lyngbyaloside C resulted in a possible stereochemical reassignment of the C11 stereogenic center
Synthesis and Biological Evaluation of Dimeric Furanoid Macroheterocycles: Discovery of New Anticancer Agents
A recently developed dimerization/macrocyclization
was employed
to synthesize a series of macroheterocycles which were biologically
evaluated, leading to the discovery of a number of potent cytotoxic
agents (e.g., <b>27</b>: GI<sub>50</sub> = 51 nM against leukemia
CCRF-CEM cell line; <b>29</b>: GI<sub>50</sub> = 99 nM against
melanoma MDA-MB-435 cell line). Further biological studies support
an apoptosis mechanism of action for these compounds involving deregulation
of the tricarboxylic acid cycle activity and suppression of mitochondrial
function in cancer cells
Synthesis and Biological Investigation of Δ<sup>12</sup>-Prostaglandin J<sub>3</sub> (Δ<sup>12</sup>-PGJ<sub>3</sub>) Analogues and Related Compounds
A series of Δ<sup>12</sup>-prostaglandin
J<sub>3</sub> (Δ<sup>12</sup>-PGJ<sub>3</sub>) analogues and
derivatives were synthesized
employing an array of synthetic strategies developed specifically
to render them readily available for biological investigations. The
synthesized compounds were evaluated for their cytotoxicity against
a number of cancer cell lines, revealing nanomolar potencies for a
number of them against certain cancer cell lines. Four analogues (<b>2</b>, <b>11</b>, <b>21</b>, and <b>27</b>)
demonstrated inhibition of nuclear export through a covalent addition
at Cys528 of the export receptor Crm1. One of these compounds (i.e., <b>11</b>) is currently under evaluation as a potential drug candidate
for the treatment of certain types of cancer. These studies culminated
in useful and path-pointing structure–activity relationships
(SARs) that provide guidance for further improvements in the biological/pharmacological
profiles of compounds within this class