Carmona-Negrón, José A.

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2013 - 20192
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    Síntesis y estudios estructurales de algunos derivados de perhidroindol
    (2013) Carmona-Negrón, José A.; Vieta, René S.; College of Arts and Sciences - Sciences; Robledo, Cynthia; Aponte, María A.; Santana, Alberto; Department of Chemistry; Sánchez, Héctor
    The biological activity of a series of alkaloids where perhydroindole is the main structural component is directly related to the geometrical isomerism of the hydrogens bound to the chiral centers. Previously, the synthesis of perhydroindole derivatives was carried out, using indoline as starting material, in one step through the reductive amination of ketones using catalytic hydrogenation as the reducing environment. Also, a series of perhydroindole derivatives has been synthesized by the Paal-Knorr reaction followed by catalytic hydrogenation of the pyrrole ring to obtain the corresponding derivative of perhydroindole. However, this method is limited to derivatives with cis configuration. In most of the mass spectra for the derivatives studied was identified, as base peak, a cation corresponding to the loss of forty-three units (M-43). The proposed fragmentation pattern suggests the abstraction of the hydrogen in position 3a as crucial step for this fragmentation. In this work, a process was developed for a diastereoselective synthesis of trans configuration perhydroindole from nonaromatic precursors. The structural studies of these derivatives were conducted by GC-MS and NMR. In addition, a derivative obtained with a phenyl substituent in position 3a of perhydroindole show evidence for the mechanism proposed above, without showing the presence of the cation M-43.
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    Synthesis, structural and cytotoxic studies of Metallocene-estrogen hormones conjugates for hormone dependent breast cancer application
    (2019) Carmona-Negrón, José A.; Meléndez, Enrique; College of Arts and Sciences - Sciences; Santana, Alberto; Pastrana, Belinda; Cortés Figueroa, José E.; Department of Chemistry; Bellido Rodríguez, Carmen M.
    In this work we present the synthesis, characterization and application of a series of ferrocene-hormone conjugates at position 16 of the estrogen hormone moiety in order to develop a new class of metal-based therapeutic drugs with high selective index for hormone dependent breast cancer application. The synthesized ferrocene-estrogen conjugates showed micromolar antiproliferative activity on hormone dependent MCF-7, T-47D, and hormone-independent MDA-MB-231 breast cancer cell lines comparable to conventional therapeutic drugs activity such as tamoxifen and cisplatin. Computational studies of the interaction of the ferrocene conjugates with estrogen receptor protein suggest the possibility of interactions of these ferrocene-hormone conjugates in the protein’s ligand binding pocket. All the functionalized ferrocene-hormone conjugates presented in this work have been characterized successfully, for the first time, by X-ray diffraction technique in order achieve precise drug structure characterization and its spatial arrangement as an important factor to understand mode of action and interaction with the estrogen receptor protein as a prerequisite for the drug development. In addition, some important inter-molecular interaction were studied in the solid state for the ferrocene-hormone conjugates. For example, an important OH-π intermolecular interaction was found in the solid state. Its description and energetic parameter was estimated by DFT methods. The interaction with Human serum albumin (HSA) protein is also presented in order to understand the biological molecular recognition between protein-ligand by fluorescence quenching iii spectroscopy. This study was aimed to determine the thermodynamics parameters involved in the molecular recognition of protein-ligand complexes. The interaction of HSA and the ferrocene-hormone conjugate is spontaneous with ΔG ~ -7.0 kcal/mol.