Three new platinum complexes containing fluoroquinolones and DMSO: Cytotoxicity and evaluation against drug-resistant tuberculosis

• Published in: Journal of inorganic biochemistry Vol. 183; pp. 77 - 83
• Main Authors: de Oliveira, Leticia P., Carneiro, Zumira A., Ribeiro, Camila M., Lima, Maurício F., Paixão, Drielly A., Pivatto, Marcos, de Souza, Marcus V.N., Teixeira, Letícia R., Lopes, Carla D., de Albuquerque, Sérgio, Pavan, Fernando R., Guerra, Wendell
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2018
• Subjects: Apoptosis; Cytotoxicity; Fluoroquinolone; Mycobacterium tuberculosis; Platinum complexes; Resistant strains; Resistant strains; Cytotoxicity; Fluoroquinolone; Mycobacterium tuberculosis; Platinum complexes; Apoptosis
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2018.03.010

This work describes the synthesis, characterization and biological evaluation of three platinum complexes of the type [Pt(DMSO)(L)Cl]Cl, in which L represents a fluoroquinolone, namely, ciprofloxacin (cpl), ofloxacin (ofl), or sparfloxacin (spf). The new complexes were characterized by elemental analysis, high-resolution mass spectrometry (HRESIMS) and 1H, 13C and 195Pt NMR (nuclear magnetic resonance). The spectral data suggest that the fluoroquinolones act as bidentate ligands coordinated to Pt(II) through the nitrogen atoms of the piperazine ring. Microbiological assays against wild type Mycobacterium tuberculosis (ATCC 27294) showed that all complexes have been very potent, exhibiting antitubercular potency at concentrations <2 μM, although none of the complexes presented higher potency than established anti-TB drugs. As to the resistant strains, the complex with sparfloxacin, [Pt(DMSO)(spf)Cl]Cl exhibited the best potential against most Mycobacterium tuberculosis clinical isolates. The cytotoxicity of these compounds was also evaluated in three breast cell lines: MCF-10 (a healthy cell), MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both tumor cell lines, [Pt(DMSO)(spf)Cl]Cl was more active and more selective than cisplatin. Flow cytometry analysis revealed that [Pt(DMSO)(spf)Cl]Cl induced late apoptotic cell death in MDA-MB-231 cells. Three platinum(II) complexes with fluoroquinolones have been synthesized and evaluated against resistant Mycobacterium tuberculosis strains and two tumor cell lines. Although none of the complexes showed higher potency than established anti-TB drugs, the complex with sparfloxacin exhibited good potential against most Mycobacterium tuberculosis clinical isolates, being more potent and selective than cisplatin toward tumor cell lines. [Display omitted] •Three Pt(II) complexes were evaluated against Mycobacterium tuberculosis and tumor cell lines.•The complexes presented potency against clinical strains of M. tuberculosis (TB).•However, the complexes are no more potent than established anti-TB drugs.•Pt(II) complex with sparfloxacin is more active and more selective than cisplatin.•Pt(II) complex with sparfloxacin induces apoptotic cell death in MDA-MB-231cells.