RT info:eu-repo/semantics/doctoralThesis
T1 Síntesis y evaluación biológica de nuevas moléculas moduladoras de los receptores de estrógenos
A1 López Rojas, Priscila
AB Selective Estrogen Receptors Modulators (SERMs) are chemical entities of lowmolecular weight that interact with estrogen receptors (ERs) and stimulate or inhibit them indifferent tissues. Tamoxifen and raloxifene are marketed SERMs that have achieved remarkablesuccess in the treatment of breast cancer and osteoporosis respectively, but they have severalside effects as endometrial cancer. Therefore, the discovery of new SERMs is of greatimportance in Medicinal Chemistry.Considering the structural features of most of the SERMs described so far and basedon the results obtained from in silico studies on ERs, three families of compounds were selectedas SERMs candidates: a) semisynthesized lignan derivatives from two natural dibenzylbutyrolactonesthrough different trasformations, incluiding deprotections of methoxy andmethylenedioxi groups, reductions, ring-opening reactions and oxidative cyclizations; b) highlyfunctionalized pyrrol-2-ones obtained from chalcones and isocyanides under microwaveirradiation; c) densely substituted pyrazoles prepared from acetophenones, aromatic aldehydesand phenyl hydrazines through a sequence of reactions that includes condensation,heterocyclation and oxidation.All compounds were tested for antiproliferative activity against ERs-positive MCF-7 andT47D breast cancer cell lines and the transcriptional activation activity was also determined inT47D-KBluc cells. In addition, binding studies and in silico ADME-Tox profile prediction werecarried out for the most potent compounds.From the obtained results some active compounds were identified as antagonist orpartial agonist/antagonist of ER. Lead compounds exhibited good drug-likeness, so they mightbe potential candidates for the clinical treatment of ERs related diseases and disorders.
YR 2022
FD 2022
LK http://riull.ull.es/xmlui/handle/915/31471
UL http://riull.ull.es/xmlui/handle/915/31471
LA es
DS Repositorio institucional de la Universidad de La Laguna
RD 08-jun-2024