Departamento Ciencias del Ambiente, Universidad de Santiago de Chile, Chile. Electronic address:
Published: August 2023
AI Article Synopsis
Article Abstract
In the search for new 5-LOX inhibitors, two ferrocenyl Schiff base complexes functionalized with catechol ((ƞ-(E)-CH-NCH-3,4-benzodiol)Fe(ƞ-CH) (3a)) and vanillin ((ƞ-(E)-CH-NCH-3-methoxy-4-phenol)Fe(ƞ-CH) (3b)) were obtained. Complexes 3a and 3b were biologically evaluated as 5-LOX inhibitors showed potent inhibition compared to their organic analogs (2a and 2b) and known commercial inhibitors, with IC = 0.17 ± 0.05 μM for (3a) and 0.73 ± 0.06 μM for (3b) demonstrated a highly inhibitory and potent effect against 5-LOX due to the incorporation of the ferrocenyl fragment. Molecular dynamic studies showed a preferential orientation of the ferrocenyl fragment toward the non-heme iron of 5-LOX, which, together with electrochemical and in-vitro studies, allowed us to propose a competitive redox deactivation mechanism mediated by water, where Fe(III)-enzyme can be reduced by the ferrocenyl fragment. An E/IC relationship was observed, and the stability of the Schiff bases was evaluated by SWV in the biological medium, observing that the hydrolysis does not affect the high potency of the complexes, making them interesting alternatives for pharmacological applications.
Alkynylallenes offer the varied reactivity patterns of two different multiple bond linkages either separately or in concert. Initially, a short overview of their syntheses, structures, rearrangement mechanisms and synthetic utility, especially when treated with transition metal reagents such as gold(I), silver(I), platinum metals or metal carbonyls, is presented. Subsequently, we focus on the particular case of 1,2-dien-5-ynes (propargylallenes), whereby the shortness of the single atom bridge, and the consequent proximity of the allenyl and alkynyl moieties, facilitates metal-mediated interactions between them.
Homotrinuclear complexes of the -symmetric tris(ferrocenyl)arene-based tris-phosphanes 1a-d with ruthenium(ii) ([1a-d(Ru)]) and rhodium(i) ([1a-d(Rh)]) were prepared and fully characterised. Complexes [1a-d(Ru)] and [1a-d(Rh)] are electrochemically active. The nature of the arene core in 1a-d ranging from benzene, 1,3,5-trifluorobenzene and mesitylene to -triazine allows to fine-tune the exact oxidation potentials for tailoring the electrochemical response.
The mol-ecular structure of 2-ferrocenyl-2-[(2-ferrocenylethen-yl)(morpholin-4-yl)meth-yl]-1,3-di-thiol-ane, [Fe(CH)(CHNOS)] or CHFeNOS, has the ferrocenyl fragments in a disposition with respect to the vinyl group. One of the methyl-ene groups is disordered over two sites with occupancies of 0.782 (13):0.
Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias y Tecnologías Químicas, IRICA, Universidad de Castilla-La Mancha, Avda. C. J Cela, 10, 13071, Ciudad Real, Spain.
Aromatase inhibitors (AIs) like Letrozole are gaining attention for treating hormone-dependent cancers, but they can cause side effects like hot flashes and fibromyalgia while posing risks such as endometrial cancer.
New AI derivatives inspired by Letrozole have been developed, particularly one with a benzimidazole ring (compound 6), which shows better aromatase inhibitory activity and reduces cancer cell growth compared to established AIs.
Compound 6 enhances binding to the aromatase enzyme due to its ferrocene structure, leading to improved interaction and increased effectiveness in inhibiting cancer cell proliferation.
In the search for new 5-LOX inhibitors, two ferrocenyl Schiff base complexes functionalized with catechol ((ƞ-(E)-CH-NCH-3,4-benzodiol)Fe(ƞ-CH) (3a)) and vanillin ((ƞ-(E)-CH-NCH-3-methoxy-4-phenol)Fe(ƞ-CH) (3b)) were obtained. Complexes 3a and 3b were biologically evaluated as 5-LOX inhibitors showed potent inhibition compared to their organic analogs (2a and 2b) and known commercial inhibitors, with IC = 0.17 ± 0.
