Antitumor and anti-Mycobacterium tuberculosis agents based on cationic ruthenium complexes with amino acids

Abstract

Six new complexes of Ru(II)/phenanthroline/1,4-bis(diphenylphosphino)butane containing amino acids (Glycine, L-Alanine, L-Valine, L-Tyrosine, L-Methionine or L-Tryptophan) were synthesized and characterized by IR, 31 P{ 1 H}, 13 C and 1 H NMR spectroscopies and cyclic voltammetry experiments. These data suggest the presence of diastereoisomers, except for the complex with glycine, amino acid that does not exhibit chiral carbon. The compounds are active against the MDA-MB-231 tumor cells and against Mycobacterium tuberculosis. The cationic ruthenium complexes with amino acids, reported here, show similar cytotoxicity against the MDA-MB-231 tumor cells. When compared with analogs complexes containing 2,2 0 -bipyridine as ligands, instead of 1,10-phenatroline, the new complexes studied here are, in general, roughly twice more active than the 2,2 0 -bipyridine ones and their IC 50 values comparable with the cisplatin. In addition, low MICs values were obtained against Mycobacterium tuberculosis compared with the reference drugs, cycloserine and ethambutol.

Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct‐[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine], by in vitro and in vivo assays

“…Our research group found that phosphinic ligands and other ligands with properties of biological interest, such as diimines, nitric oxide, carbon monoxide (CO) and amino acids coordinated to the ruthenium metal center, exhibited relevant characteristics in different biological assays (Barbosa et al, ; Lima et al, ; Mondelli et al, ; Oliveira et al, ; Porto et al, ; Santos et al, ). We have recently published a study demonstrating the antitumor activity of the ruthenium(II) compound, ct‐ [RuCl(CO)(dppb)(bipy)]PF 6 (where dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine), in in vitro and in vivo assays, as well as its interactions with ctDNA and bovine serum albumin.…”

Development of Natural Product-Conjugated Metal Complexes as Cancer Therapies

“…These conjugates demonstrated a better activity against breast cancer cells compared to the reference drug cisplatin and the non-amino acid conjugate ruthenium(II) complex, with an IC 50 ranging from 3.04 to 7.44 µM. Among all of the developed compounds, complex 5c bearing the Tyr residue exhibited the best activity [66].…”

“…The binding affinity towards targeted active sites is of great importance for cancer therapy development based on the similar hydrophilic–lipophilic ability of the treatment molecule and the corresponding targeting receptors [66]. Ruiz and coworkers recently developed a lipophilic levonorgestrel-conjugated ruthenium(II) complex 7a (Figure 8) against breast cancer [67].…”

New Heteroleptic RuII/Diphosphine Complexes with Cytotoxicity against Human Breast and Murine Ascitic Sarcoma 180 Tumor Cells

“…3 Recently, a great number of ruthenium complexes containing different ligands, have been tested as antitumor agents against different kinds of tumor cell lines, showing to be very active. [4][5][6][7][8][9] Thus, picolinate containing complex [Ru(η 6 -p-cymene)Cl(picolinate)] is active against HeLa (drug concentration at which 50% of the cells are viable relative to the control (IC 50 ) = 82.0 μM) and human melanoma cells (FemX, IC 50 = 36.2 μM). 10 The possible reason for this behavior is that the [Ru(η 6 -p-cymene) Cl(picolinate)] accumulates in the deoxyribonucleic acid (DNA) molecule, since it has high affinity for DNA-binding.…”