Eight new copper(II) complexes with halo-aspirinate anions have been synthesized: Cu
2
(Fasp)
4
(MeCN)
2
· 2MeCN (1), Cu
2
(Clasp)
4
(MeCN)
2
· 2MeCN (2), Cu
2
(Brasp)
4
(MeCN)
2
· 2MeCN (3), {Cu
...2
(Fasp)
4
(Pyrz) · 2MeCN}
n
(4), {Cu
2
(Clasp)
4
(Pyrz) · 2MeCN}
n
(5), Cu
2
(Brasp)
4
(Pyrz)
n
(6), Cu
2
(Clasp)
4
(4,4′-Bipy)
n
(7), and Cu
2
(Brasp)
4
(4,4′-Bipy)
n
(8) (Fasp: fluor-aspirinate; Clasp: chloro-aspirinate; Brasp: bromo-aspirinate; MeCN: acetonitrile; Pyrz: pyrazine; 4,4′-Bipy: 4,4′-bipyridine). The crystal structure of two 2 and 4 have been determined by X-ray diffraction methods. All compounds have been studied employing elemental analysis, IR, and UV-Visible spectroscopic techniques. The results have been compared with previous data reported for complexes with similar structures.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human ...epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-Ru(PPh
)
(N,N-dibutyl-N'-benzoylthioureato-k
O,S)(2,2'-bipyridine (bipy))PF
(1), trans-Ru(PPh
)
(N,N-dimethyl-N'-thiophenylthioureato-k
O,S)(bipy)PF
(2) and trans-Ru(PPh
)
(N,N-dimethyl-N'-benzoylthioureato-k
O,S)(bipy)PF
(3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Herein, new palladium(II) complexes with Schiff bases derived from salicylaldehyde and N,N-dialkyl-p-phenylenediamines were obtained. The ligands 2-((4-(N,N-dimethylamino)aniline)formimidoyl)phenol ...(N,N-metph-sOH - L1) and 2-((4-(N,N-diethylamino)aniline)formimidoyl)phenol (N,N-etph-sOH - L2) and complexes Pd(N,N-metph-sO)2 (C1) and Pd(N,N-etph-sO)2 (C2) were characterized by elemental analysis, infrared (IR) and UV–Vis spectroscopy, 1H and 13C nuclear magnetic resonance (NMR), thermogravimetry (TG) and differential thermal analysis (DTA), and the results agree with the proposed structures. The crystal structures data showed the formation of N,O-chelate with the pairs of phenolate O and imine N occupying the trans positions. Hirshfeld surface analysis was employed to elucidate the intermolecular contacts which drive the different supramolecular assemblies of C1 and C2. In addition, Density Functional Theory (DFT) calculations were also performed to better understand the electronic properties. Additional DFT calculations were also devoted to elucidate the stereochemistry of these palladium complexes toward the cis-trans isomerism among these square-planar Pd(II) N,O-Schiff base complexes. Time-dependent DFT (TD-DFT) analysis was applied to shed light on the nature of the electronic transitions determined in the UV–Vis spectra.
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•Two new Schiff base Pd(II) N,O-chelate complexes were synthetized.•Used ligands were derived from N,N-dialkyl-p-phenylenediamines and salicylaldehyde.•Spectroscopic, thermal and elemental analyzes agree with the proposed structures.•The crystal structures and Hirshfeld surface analysis of the new complexes were determined by X-ray diffraction.•Pd(II) complexes stereochemistry and UV–Vis spectra were elucidated by DFT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human ...epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-Ru(PPh3)2(N,N-dibutyl-N′-benzoylthioureato-k2O,S)(2,2′-bipyridine (bipy))PF6(1), trans-Ru(PPh3)2(N,N-dimethyl-N′-thiophenylthioureato-k2O,S)(bipy)PF6(2) and trans-Ru(PPh3)2(N,N-dimethyl-N′-benzoylthioureato-k2O,S)(bipy)PF6(3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice.
Complex 2 induces DNA damage and apoptosis, inhibits cell proliferation, colony formation, adhesion, invasion and migration of MDA-MB-231 triple negative breast tumor cancer (TNBC) cells. In addition, complex 2 induces intense morphological changes and arrests cell cycle at sub-G1 phase in TNBC cells, with low toxicity and genotoxicity in vivo. Display omitted
•New trans-Ru(PPh3)2(acylthioureato-k2O,S)(2,2′-bipyridine)PF6 complexes are presented.•Complex (2) had effective action for triple negative breast cancer (TNBC) cells.•Complex (2) inhibited several cellular processes in TNBC cells.•In vivo complex (2) did not induce toxicity and induce low DNA damage.•Complex (2) has potential to be used cancer therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this study, novel ruthenium(
iii
) complexes with hydroxybenzophenones with the general formula
cis
-RuCl
2
(HB)(dppb) were obtained, where
HB
= 2-hydroxy-4-(octyloxy)benzophenone (
C1
), ...2-hydroxy-4-methoxybenzophenone (
C2
), 2,2′-dihydroxy-4,4′-dimethoxybenzophenone (
C3
), 2,2′-dihydroxy-4-methoxybenzophenone (
C4
), 2,4-dihydroxybenzophenone (
C5
), and 2,4,4′-trihydroxybenzophenone (
C6
), and
dppb
= 1,4-bis(diphenylphosphine)butane. These compounds were characterized by elemental analysis, molar conductivity, cyclic voltammetry, infrared and UV-vis spectroscopy, and powder X-ray diffraction. The crystal structures of
C2
,
C3
,
C4
, and
C5
were determined by single-crystal X-ray diffraction analysis which confirmed the bidentate coordination of the carbonyl and phenolate oxygens of
HB
with ruthenium(
iii
). Additionally, the
cis
geometry and electronic transitions of
C1-C6
were investigated using DFT calculations. Finally, the comparative activity against promastigote forms of
L. amazonensis
was made available for the ligands
HB1-HB6
and
C1-C6
. The ligands significantly inhibited the proliferation of promastigote forms, confirming the results previously published by some of us. Unfortunately, their respective complexes showed no activity. It is important to emphasize that the leishmanicidal activity of 2,2′-dihydroxy-4,4′-dimethoxybenzophenone (
HB3
), 2,2′-dihydroxy-4-methoxybenzophenone (
HB4
), and 2,4,4′-trihydroxybenzophenone (
HB6
) ligands is reported here for the first time. Despite the fact that they were less active against promastigote forms when compared to amphotericin B, two of them (
HB4
and
HB6
) were less cytotoxic to J774 macrophages.
Six ruthenium-benzophenone complexes were synthesized in order to combine the chemistry of two interesting compound classes aiming at medicinal chemistry innovation.
The nitrososulfonate ion (N(O)SO3−) has been proposed to be formed in stomach by the reaction of nitrite and sulfite ions. Nevertheless, very little is known about the chemistry of N(O)SO3−, which is ...unstable and generates reactive species. Aiming to provide a better knowledge on the chemistry and biological relevance of the N(O)SO3−, we synthesized a nitrosylsulphito complex trans-Ru(NH3)4(isn)(N(O)SO3)+ (isn=isonicotinamide) as a stable and delivery agent of N(O)SO3− via photoactivation. This complex was characterized by spectroscopic means, single-crystal X-ray diffraction, and supported by DFT calculations. Electronic and NMR spectroscopy revealed that trans-Ru(NH3)4(isn)(N(O)SO3)+ is stable in phosphate buffer with a k = 3.0×10-5s-1 (t1/2~385 min, at 25 °C) for isn labilization. At acidic conditions (1.0 M HTFA) trans-Ru(NH3)4(isn)(N(O)SO3)+ is found to be converted back to the synthetic precursor trans-Ru(NH3)4(isn)(NO)3+. This process is proposed to be related to the protonation of the SO3 fragment in the coordinated N(O)SO3 ligand (pKa~5) favoring the S–N bond cleavage. An intense absorption band at 363 nm (ε=6.0×103M−1cm−1) observed for trans-Ru(NH3)4(isn)(N(O)SO3)+ was assigned by DFT as a metal-to-ligand charge transfer (Ru→N(O)SO3) transition. Upon photolysis at 355 nm in phosphate buffer, trans-Ru(NH3)4(isn)(N(O)SO3)+ releases NO and SO3●−, by a probable mechanism in which N(O)SO3− ligand is photoreleased and further dissociates into NO• and SO3●− species. SO3●– is one of the few sulfur radical species found in cells, which despite its relative low reduction potential (Eº~0.63 V) may promote oxidative damage by acting as a prooxidant and precursor of sulfate radical (SO4●–), a strong oxidant (Eº ~ 2.5 V vs. NHE). Thus, the newly synthesized nitrosylsulphito complex seems to be a valuable source of N(O)SO3−, nitric oxide and sulfite radical (SO3●–).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PAMAM dendrimer functionalized with ruthenium nitrosyl complexes (NO-donors), which can release nitric oxide on a controlled way when triggered either by light irradiation or by chemical reduction. ...Display omitted
•PAMAM were functionalized with ruthenium nitrosyl complexes in one-step synthesis.•Functionalization did not alter the ruthenium nitrosyl properties.•Nitric oxide can be released when triggered by light or by one-electron reduction.•PAMAM can storage high concentrations of NO on a single framework.
The functionalization of three generations of polyamidoamine (PAMAM G0, G2 and G3) dendrimers with the NO-donor trans-Ru(NO)(NH3)4(ina)(BF4)3 (ina=isonicotinic acid) is reported. PAMAMs were modified through a peptide-type bond between the carboxyl group of the ina ligand and the dendrimer superficial amines. Compounds were characterized by FT-IR, UV–Vis, CV, DPV, 1H NMR, ICP-OES, and the structure of the complextrans-Ru(NO)(NH3)4(ina)(BF4)(SiF6)·H2O was determined by single crystal X-Ray analysis. The experimental data indicated the immobilization of 4, ∼8 and ∼27 nitrosyl complexes on the G0, G2 and G3 dendrimer’s surface, respectively, which corresponds to ∼1.0–1.43μmol NO per mg of dendrimer. FT-IR, UV–Vis and electrochemical assays suggest that the functionalization of PAMAM did not alter the coordination sphere of the ruthenium nitrosyl complex neither the formal reduction potential of RuIINO+/RuIINO0 couple regarding to the complex not attached to PAMAM. The NO release in these compounds, through light irradiation (λ=355nm) and one-electron reduction (Eu2+), was investigated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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