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Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling

Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well-defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecul...

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Autores principales: Gabriel, Catherine, Tsave, Olga, Yavropoulou, Maria P., Architektonidis, Theodore, Raptopoulou, Catherine P., Psycharis, Vassilis, Salifoglou, Athanasios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268141/
https://www.ncbi.nlm.nih.gov/pubmed/34201755
http://dx.doi.org/10.3390/ijms22136757
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author Gabriel, Catherine
Tsave, Olga
Yavropoulou, Maria P.
Architektonidis, Theodore
Raptopoulou, Catherine P.
Psycharis, Vassilis
Salifoglou, Athanasios
author_facet Gabriel, Catherine
Tsave, Olga
Yavropoulou, Maria P.
Architektonidis, Theodore
Raptopoulou, Catherine P.
Psycharis, Vassilis
Salifoglou, Athanasios
author_sort Gabriel, Catherine
collection PubMed
description Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well-defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecular research linked to zinc metallodrugs. To that end, meticulous efforts were launched toward the design and synthesis of materials with insulin mimetic potential. Henceforth, trigonelline and N-(2-hydroxyethyl)-iminodiacetic acid (HeidaH(2)) were selected as organic substrates seeking binding to zinc (Zn(II)), with new crystalline compounds characterized by elemental analysis, FT-IR, X-rays, thermogravimetry (TGA), luminescence, NMR, and ESI-MS spectrometry. Physicochemical characterization was followed by in vitro biochemical experiments, in which three out of the five zinc compounds emerged as atoxic, exhibiting bio-activity profiles reflecting enhanced adipogenic potential. Concurrently, well-defined qualitative–quantitative experiments provided links to genetic loci responsible for the observed effects, thereby unraveling their key involvement in signaling pathways in adipocyte tissue and insulin mimetic behavior. The collective results (a) signify the quintessential role of molecular studies in unearthing unknown facets of pathophysiological events in diabetes mellitus II, (b) reflect the close associations of properly configured molecular zincoforms to well-defined biological profiles, and (c) set the stage for further physicochemical-based development of efficient zinc antidiabetic metallodrugs.
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spelling pubmed-82681412021-07-10 Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling Gabriel, Catherine Tsave, Olga Yavropoulou, Maria P. Architektonidis, Theodore Raptopoulou, Catherine P. Psycharis, Vassilis Salifoglou, Athanasios Int J Mol Sci Article Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well-defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecular research linked to zinc metallodrugs. To that end, meticulous efforts were launched toward the design and synthesis of materials with insulin mimetic potential. Henceforth, trigonelline and N-(2-hydroxyethyl)-iminodiacetic acid (HeidaH(2)) were selected as organic substrates seeking binding to zinc (Zn(II)), with new crystalline compounds characterized by elemental analysis, FT-IR, X-rays, thermogravimetry (TGA), luminescence, NMR, and ESI-MS spectrometry. Physicochemical characterization was followed by in vitro biochemical experiments, in which three out of the five zinc compounds emerged as atoxic, exhibiting bio-activity profiles reflecting enhanced adipogenic potential. Concurrently, well-defined qualitative–quantitative experiments provided links to genetic loci responsible for the observed effects, thereby unraveling their key involvement in signaling pathways in adipocyte tissue and insulin mimetic behavior. The collective results (a) signify the quintessential role of molecular studies in unearthing unknown facets of pathophysiological events in diabetes mellitus II, (b) reflect the close associations of properly configured molecular zincoforms to well-defined biological profiles, and (c) set the stage for further physicochemical-based development of efficient zinc antidiabetic metallodrugs. MDPI 2021-06-23 /pmc/articles/PMC8268141/ /pubmed/34201755 http://dx.doi.org/10.3390/ijms22136757 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gabriel, Catherine
Tsave, Olga
Yavropoulou, Maria P.
Architektonidis, Theodore
Raptopoulou, Catherine P.
Psycharis, Vassilis
Salifoglou, Athanasios
Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling
title Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling
title_full Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling
title_fullStr Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling
title_full_unstemmed Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling
title_short Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling
title_sort evaluation of insulin-like activity of novel zinc metal–organics toward adipogenesis signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268141/
https://www.ncbi.nlm.nih.gov/pubmed/34201755
http://dx.doi.org/10.3390/ijms22136757
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