A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity.

A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity. J Inorg Biochem. 2020 Jun 20;210:111133 Authors: Carvalho EM, Ridnour LA, Júnior FSG, Cabral PHB, do Nascimento NRF, Wink DA, Franco DW, de Medeiros MJC, de Lima Pontes D, Longhinotti E, de Freitas Paulo T, Bernardes-Génisson V, Chauvin R, Sousa EHS, Lopes LGF Abstract Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors. However, in both cases there is an expressive lack of iron-based compounds. Herein, we explored the novel chemical reactivity and stability of the trans-[Fe(cyclam)(NO)Cl]Cl2 (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex. Interestingly, the half-life (t1/2) for NO release was 1.8 min upon light irradiation, vs 5.4 h upon thermal activation at 37 °C. Importantly, spectroscopic evidence supported the generation of HNO rather than NO induced by glutathione. Moreover, we observed significant inhibition of NO donor- or hypoxia-induced HIF-1α (hypoxia-inducible factor 1α) accumulation in breast cancer cells, as well as reduced vascular tube fo...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research