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Authors: Kostrzewa, Tomasz
Jończyk, Jakub
Drzeżdżon, Joanna
Jacewicz, Dagmara
Górska-Ponikowska, Magdalena
Kołaczkowski, Marcin
Kuban-Jankowska, Alicja
Title: Synthesis, in vitro, and computational studies of PTP1B phosphatase inhibitors based on oxovanadium(IV) and dioxovanadium(V) complexes
Issue Date: 2022 Zeitschriftenartikel 19 International journal of molecular sciences 23 (2022), No. 7034
ISSN: 1422-0067
Abstract: One of the main goals of recent bioinorganic chemistry studies has been to design and synthesize novel substances to treat human diseases. The promising compounds are metal-based and metal ion binding components such as vanadium-based compounds. The potential anticancer action of vanadium-based compounds is one of area of investigation in this field. In this study, we present five oxovanadium(IV) and dioxovanadium(V) complexes as potential PTP1B inhibitors with anticancer activity against the MCF-7 breast cancer cell line, the triple negative MDA-MB-231 breast cancer cell line, and the human keratinocyte HaCaT cell line. We observed that all tested compounds were effective inhibitors of PTP1B, which correlates with anticancer activity. [VO(dipic)(dmbipy)]·2 H2O (Compound 4) and [VOO(dipic)](2-phepyH)·H2O (Compound 5) possessed the greatest inhibitory effect, with IC50 185.4 ± 9.8 and 167.2 ± 8.0 nM, respectively. To obtain a better understanding of the relationship between the structure of the examined compounds and their activity, we performed a computer simulation of their binding inside the active site of PTP1B. We observed a stronger binding of complexes containing dipicolinic acid with PTP1B. Based on our simulations, we suggested that the studied complexes exert their activity by stabilizing the WPD-loop in an open position and limiting access to the P-loop.
Appears in Collections:04 Fakultät Energie-, Verfahrens- und Biotechnik

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