Osmium(IV) complexes with 1H- and 2H-indazoles: Tautomer identity versus spectroscopic properties and antiproliferative activity

Abstract

A one-pot synthesis of osmium(IV) complexes with two different tautomers of indazole, 1H-indazole and 2H-indazole, namely (H2ind)[OsIVCl5(2H-ind)] (1) and (H2ind)[OsIVCl5(1H-ind)] (2) is reported. Both compounds have been comprehensively characterized by NMR spectroscopy, ESI (electrospray ionization) mass spectrometry, electronic absorption spectroscopy, IR spectroscopy, cyclic voltammetry and tested for antiproliferative activity in vitro in three human cancer cell lines, CH1 (ovarian carcinoma), A549 (non-small cell lung cancer) and SW480 (colon carcinoma), as well as in vivo in a Hep3B SCID mouse xeno-transplantation model. 2H-Indazole tautomer stabilization in 1 has been confirmed by X-ray diffraction.

Anticancer Organometallic Osmium(II)‐p‐cymene Complexes

“…[2] For compounds with chloridec o-ligands, aquation is usually considered to take place following uptake into ac ell,a ctivating the complex, allowingt he compound to undergo reactionw ith biomolecular targets. [18-20, 30, 31] Notably,anumber of osmium complexes have been evaluatedi nv ivoi ncluding osmium(IV)indazolec omplexes, [32] an itridoosmium(VI) complex, [33] osmium(II)-arene complexes, [24][25][26] and an osmium-carbonyl cluster ( Figure 2). [18-20, 30, 31] Notably,anumber of osmium complexes have been evaluatedi nv ivoi ncluding osmium(IV)indazolec omplexes, [32] an itridoosmium(VI) complex, [33] osmium(II)-arene complexes, [24][25][26] and an osmium-carbonyl cluster ( Figure 2).…”

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

“…These complexes were studied for their antiproliferative activity in vitro and in vivo (Scheme 2). 16, 57 …”

“…The 1 H -indazole is the dominant tautomer in the gas phase and aqueous solution, 11, 12 as well as in metal complexes, however, some substituted organic 2 H -indazoles are known 13 as well as rare, inorganic examples such as an organoruthenium(II) complex with 2-methyl-indazole, 14 and the osmium(IV) complexes trans -[Os IV Cl 4 (κN1-2 H -ind) 2 ], 15 and (H 2 ind)[Os IV Cl 5 (κN1-2 H -ind)]. 16 The synthesis of the latter complex along with (H 2 ind)[Os IV Cl 5 (κN2-1 H -ind)] made an estimation of the effect of indazole tautomer identity on the antiproliferative activity of osmium(IV) complexes in different human cancer cell lines possible.…”

Elements toward novel therapeutic targeting of the adrenergic system

“…Moreover, it has been shown that in neonates, activators of both β1-ARs and β2-ARs represent potential neuro-protective agents (Markus et al, 2010), whereas others have indicated that co-treatment combining both β2-ARs agonists and β1-ARs antagonists may increase the cerebroprotective properties of β2-ARs agonists in vivo (Junker et al, 2002). In addition to previous studies that have highlighted noradrenergic system's neuroprotective properties (Chen et al, 2007;Heneka et al, 2002;Madrigal et al, 2007;Traver et al, 2005;Troadec et al, 2001), β1-ARs stimulation results in the translation of striatal enriched protein tyrosine phosphatase (Buchel et al, 2012), which exists in several brain structures. This has been linked to the learning process (Hu et al, 2007) again expanding the neuropharmacological area of targeting the adrenergic system.…”