Organometallic anticancer complexes of lapachol: metal centre-dependent formation of reactive oxygen species and correlation with cytotoxicity

Abstract

Organometallic Ru(II), Os(II) and Rh(III) complexes of lapachol induce apoptosis in human tumour cell lines in the low μM range by a mode of action involving oxidative stress, especially in the case of the ruthenium compound.

Crystal structure of bromido(η6-1-isopropyl-4-methylbenzene)(7-oxocyclohepta-1,3,5-trien-1-olato-κ2O,O′)osmium

“…The isobidentate nature of the OsO 2 C 2 moiety is evidence of delocalization of the C O bonds of the tropolone ligand upon coordination [C11-O1 = 1.303 (11), C17-O2 = 1.299 (11)Å ]. The aromatic ring of the p-cymene ligand appears almost planar, with the displacement of the arene ring centroid from the Os II center [1.676 Å ] being comparable with other similar complexes (Peacock et al, 2007;Kandioller et al 2013).…”

“…Only one orientation of the disordered benzene ring is shown. Kandioller et al, 2013) have been reported.…”

Antiparasitic activities of novel ruthenium/lapachol complexes

“…The aromatic C\H hydrogen atoms were positioned stereochemically and were refined with fixed individual displacement parameters [U iso (H) = 1.2 U eq (Csp 2 )] using a riding model with an aromatic, C\H bond length fixed at 0.93 Å. Methylene groups of the dppb ligand in the complex (5), and methine group of the lapachol were set as isotropic with a thermal parameter 20% greater than the equivalent isotropic displacement parameter of the atom to which each one was bonded, whereas methyl groups were set with U iso (H) values of 1.5U eq (C methyl ). Tables were generated by WinGX [25] and the structure representations by ORTEP-3 [18] and MERCURY [21]. The main crystal data collections and structure refinement parameters for (1) and (5) are summarized in Table 1.…”

“…In fact, there are some findings showing that lapachol-metal complexes are biologically more active than the free molecule [15][16][17][18]. Ruthenium complexes are considered to be one of the most promising types of metal compounds for cancer treating, due its interesting chemical properties, such as: versatility in ligand exchange, octahedral geometry and variability of oxidation states [19,20].…”

“…Ruthenium complexes are considered to be one of the most promising types of metal compounds for cancer treating, due its interesting chemical properties, such as: versatility in ligand exchange, octahedral geometry and variability of oxidation states [19,20]. Recently it was observed that the lapachol-Ru(II) complex is a more potent anticancer agent than lapachol-Os(II) and Rh(III) complexes [18], suggesting that the use of ruthenium is promising to improve the biological activity of lapachol.…”