Lapachol in the Design of a New Ruthenium(II)-Diphosphine Complex as a Promising Anticancer Metallodrug

Oliveira, Katia M.; Honorato, João; Demidoff, Felipe C.; Schultz, Mário Sérgio; Netto, Chaquip D.; Cominetti, Márcia Regina; Corrêa, Rodrigo S.; Batista, Alzir A.

doi:10.1016/j.jinorgbio.2020.111289

Cited by 26 publications

(7 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar pattern was observed for the ruthenium complexes [Ru(Lap)(dppm) 2 ]PF 6 and [Ru(Law)(dppm) 2 ]PF 6 , where dppm = 1,1 0 -bis(diphenylphosphino)methane, and Lap and Law are naphthoquinones, lapachol and lawsone, respectively. 34 It is also worth pointing out that the lengths of the Fe-O bonds (see Table 2) are very close for both oxygen atoms, confirming the suggestion of resonance in the 1,4-dihydroxyantraquinone coordinated ligand.…”

Section: Resultssupporting

confidence: 68%

A binuclear Fe(iii)/quinizarin complex as a structural model for anthracycline drugs binding to iron

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Resultssupporting

confidence: 68%

A binuclear Fe(iii)/quinizarin complex as a structural model for anthracycline drugs binding to iron

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Over a 12 h kinetic study in MDA-MB-231 cells with nontreated cells as a negative control and 1 mM hydrogen peroxide (H 2 O 2 ) as a positive control, 1 showed significant ( p < 0.001) ROS generation upon treatment using an IC 50 value of the complex. This generation of ROS is comparable to that of other ROS-producing ruthenium complexes, such as ruthenium(II) cationic compounds like [Ru-ATZ] + containing cyclopentadienyl, [Ru(Lap)(dppm) 2 ]PF 6 containing lapachol, and [RuNO(bpy) 2 (4-pic)](PF 6 ) 3 encapsulated in liposomes, or that of anionic ruthenium(III) derivative BOLD-100 (currently in clinical trials) . For most anticancer drugs that generate ROS and provoke apoptosis, there is an activation of intrinsic pathways that involves an increase of the mitochondrial permeability, the release of activator factors, and the activation of caspases .…”

Section: Resultsmentioning

confidence: 71%

Intracellular Localization Studies of the Luminescent Analogue of an Anticancer Ruthenium Iminophosphorane with High Efficacy in a Triple-Negative Breast Cancer Mouse Model

et al. 2021

View full text Add to dashboard Cite

The potential of ruthenium(II) compounds as an alternative to platinum-based clinical anticancer agents has been unveiled after extensive research for over 2 decades. As opposed to cisplatin, ruthenium(II) compounds have distinct mechanisms of action that do not rely solely on interactions with DNA. In a previous report from our group, we described the synthesis, characterization, and biological evaluation of a cationic, water-soluble, organometallic ruthenium(II) iminophosphorane (IM) complex of p-cymene, ([(η6-p-cymene)Ru{(Ph3PN-CO-2N-C5H4)-κ-N,O}Cl]Cl (1 or Ru-IM), that was found to be highly cytotoxic against a panel of cell lines resistant to cisplatin, including triple-negative breast cancer (TNBC) MDA-MB-231, through canonical or caspase-dependent apoptosis. Studies on a MDA-MB-231 xenograft mice model (after 28 days of treatment) afforded an excellent tumor reduction of 56%, with almost negligible systemic toxicity, and a favored ruthenium tumor accumulation compared to other organs. 1 is known to only interact weakly with DNA, but its intracellular distribution and ultimate targets remain unknown. To gain insight on potential mechanisms for this highly efficacious ruthenium compound, we have developed two luminescent analogues containing the BOPIPY fluorophore (or a modification) in the IM scaffold with the general structure of [(η6-p-cymene)Ru{(BODIPY-Ph2PN-CO-2-NC5H4)-κ-N,O}Cl]Cl {BODIPY-Ph2P = 8-[(4-diphenylphosphino)phenyl]-4,4-dimethyl-1,3,5,7-tetramethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene (3a) and 4,4-difluoro-8-[4-[[2-[4-(diphenylphosphino)benzamido]ethyl]carbamoyl]phenyl]-1,3,5,7-tetramethyl,2,6-diethyl-4-bora-3a,4a-diaza-s-indacene (3b)}. We report on the synthesis, characterization, lipophilicity, stability, luminescence properties, and cell viability studies in the TNBC cell line MDA-MB-231, nonmalignant breast cells (MCF10a), and lung fibroblasts (IMR-90) of the new compounds. The ruthenium derivative 3b was studied by fluorescence confocal microscopy. These studies point to a preferential accumulation of the compound in the endoplasmic reticulum, mitochondria, and lysosomes. Inductively coupled plasma optical emission spectrometry (ICP-OES) analysis also confirms a greater ruthenium accumulation in the cytoplasmic fraction, including endoplasmic reticulum and lysosomes, and a smaller percentage of accumulation in mitochondria and the nucleus. ICP-OES analysis of the parent compound 1 indicates that it accumulates preferentially in the mitochondria and cytoplasm. Subsequent experiments in 1-treated MDA-MB-231 cells demonstrate significant reactive oxygen species generation.

show abstract

“…Oliveira et al prepared two Ru(II)-diphosphine complexes, containing lapachol and lawsone as ligands [ 74 ]. Both complexes were highly cytotoxic against the MDA-MB-231, MCF-7, A549 and DU-145 (prostate) cancer cell lines with IC 50 values in the low micromolar range (IC 50 = 0.03–2.70 μM).…”

Section: Novel Metal Complexes In Cancer Therapymentioning

confidence: 99%

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

Todorov

Kostova

2023

Molecules

View full text Add to dashboard Cite

Since the accidental discovery of the anticancer properties of cisplatin more than half a century ago, significant efforts by the broad scientific community have been and are currently being invested into the search for metal complexes with antitumor activity. Coordination compounds of transition metals such as platinum (Pt), ruthenium (Ru) and gold (Au) have proven their effectiveness as diagnostic and/or antiproliferative agents. In recent years, experimental work on the potential applications of elements including lanthanum (La) and the post-transition metal gallium (Ga) in the field of oncology has been gaining traction. The authors of the present review article aim to help the reader “catch up” with some of the latest developments in the vast subject of coordination compounds in oncology. Herewith is offered a review of the published scientific literature on anticancer coordination compounds of Pt, Ru, Au, Ga and La that has been released over the past three years with the hope readers find the following article informative and helpful.

show abstract

Lapachol in the Design of a New Ruthenium(II)-Diphosphine Complex as a Promising Anticancer Metallodrug

Cited by 26 publications

References 58 publications

A binuclear Fe(iii)/quinizarin complex as a structural model for anthracycline drugs binding to iron

A binuclear Fe(iii)/quinizarin complex as a structural model for anthracycline drugs binding to iron

Intracellular Localization Studies of the Luminescent Analogue of an Anticancer Ruthenium Iminophosphorane with High Efficacy in a Triple-Negative Breast Cancer Mouse Model

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

Contact Info

Product

Resources

About