28336-29-0Relevant articles and documents
A Minimalist Approach to the Design of Complexity-Enriched Bioactive Small Molecules: Discovery of Phenanthrenoid Mimics as Antiproliferative Agents
Alonso, Fernando,Quezada, María Josefina,Gola, Gabriel F.,Richmond, Victoria,Cabrera, Gabriela M.,Barquero, Andrea A.,Ramírez, Javier A.
, p. 1732 - 1740 (2018)
Over the last decades, much effort has been devoted to the design of the “ideal” library for screening, the most promising strategies being those which draw inspiration from biogenic compounds, as the aim is to add biological relevance to such libraries. On the other hand, there is a growing understanding of the role that molecular complexity plays in the discovery of new bioactive small molecules. Nevertheless, the introduction of molecular complexity must be balanced with synthetic accessibility. In this work, we show that both concepts can be efficiently merged—in a minimalist way—by using very simple guidelines during the design process along with the application of multicomponent reactions as key steps in the synthetic process. Natural phenanthrenoids, a class of plant aromatic metabolites, served as inspiration for the synthesis of a library in which complexity-enhancing features were introduced in few steps using multicomponent reactions. These resulting chemical entities were not only more complex than the parent natural products, but also interrogated an alternative region of the chemical space, which led to an outstanding hit rate in an antiproliferative assay: four out of twenty-six compounds showed in vitro activity, one of them being more potent than the clinically useful drug 5-fluorouracil.
Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents
Alsayari, Abdulrhman,Kopel, Lucas,Ahmed, Mahmoud Salama,Pay, Adam,Carlson, Taylor,Halaweish, Fathi T.
, p. 32 - 40 (2016/12/23)
Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-α (ER-α) and Estrogen Receptor-β (ER-β) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49 μM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-β; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-α.
Anionic Fries Rearrangements of Esters of ortho-Iodobenzyl Alcohols: Rapid Routes to Oestrone Methyl Ether and Its 9β Epimer, and Aryl Naphthalide Lignans
Horne, Stephen,Rodrigo, Russell
, p. 164 - 166 (2007/10/02)
A fast, general, low-temperature rearrangement of ortho-iodobenzyl esters, triggered by lithium-iodine exchange, leads to isobenzofurans which are intercepted in situ by inter and intramolecular Diels-Alder (IMDA) reactions to produce a variety of carbocycles including natural lignans and steroids.
