Design, synthesis, structural characterization and in vitro cytotoxic activity of mononuclear Ru(II)complexes

Article abstract of DOI:10.1007/s00044-016-1625-8

The synthesis and characterization of ruthenium complexes (Ru-1–Ru-6) of the type [Ru(R)₂(K)]²⁺ (where R = 1,10-phenanthroline/2,2′-bipyridyl and K = acetyl coumarin-inh, pyrazole-tch, acetyl coumarin-tsz, are described. These ligand

Full text of DOI:10.1007/s00044-016-1625-8

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-016-1625-8
ORIGINAL RESEARCH
Design, synthesis, structural characterization and in vitro cytotoxic
activity of mononuclear Ru(II)complexes
1,2
Srujana Vallala3 Rajeshwar Yerra3
●
●
●
Sreekanth Thota
Daniel Alencar Rodrigues2 Eliezer J. Barreiro2
●
Received: 16 October 2014 / Accepted: 27 June 2016
© Springer Science+Business Media New York 2016
Abstract The synthesis and characterization of ruthenium
complexes (Ru-1–Ru-6) of the type [Ru(R)2(K)]2+ (where
R = 1,10-phenanthroline/2,2′-bipyridyl and K = acetyl
coumarin-inh, pyrazole-tch, acetyl coumarin-tsz, are
described. These ligands form bidentate octahedral ruthe-
nium complexes. The in vitro cytotoxic activities of the
complexes measurement against the human cancer T-
lymphocyte cell lines. In vitro evaluation of these title
complexes revealed cytotoxicity from 0.34 to 1.4 µg/mL
against CEM, 0.28 to 1.8 µg/mL against L1210, 0.44 to 2.5
µg/mL against Molt4/C8, 0.98 to 1.6 µg/mL against HL60,
and 0.66 to 1.4 µg/mL against BEL7402. Ruthenium com-
plexes Ru-5 & Ru-6 showed that quite significant antic-
ancer activities over standard drugs.
Introduction
Research on drugs based on ruthenium complexes is a fast
developing field in medicine, especially in development of
chemotherapeutic agents with less side effects and immu-
nity to acquisition of drug resistance. (Muggia, 2009) The
synthesis of ruthenium complexes with thiosemicarbazone
ligands has been receiving considerable attention due to the
pharmacological properties of both complexes & ligands.
(Beckford et al., 2009; Mazumder et al., 2005; Thota et al.,
2012) Thiosemicarbazone ligands exhibit a wide variety of
biological activities such as antiviral (Finkielsztein et al.,
2008), antitumor (Patel and Divatia, 2013), antibacterial
(Agarwal et al., 2006), and antifungal properties (Costa
et al., 2005). The thiosemicarbazone ligands usually coor-
dinate to ruthenium through Nitrogen & Sulfur donor
atoms in their (N, S) bidentate form. (Thota et al., 2013;
El-shazly et al., 2006) Recently, two Ru(III) compounds,
namely, KP1019 (indazolium trans-[tetrachloro bis (1H-
indazole) ruthenate(III)] (Hartinger et al., 2008) and NAMI-
A (imidazolium trans-[tetrachloro(dimethylsulfoxide)(1H-
imidazole)-ruthenate(III)] entered phase II clinical trials as
antimetastatic compounds.
●
●
Keywords Acetyl coumarin Ruthenium complexes
Cytotoxicity
* Sreekanth Thota
sthota@cdts.fiocruz.br
A series of ruthenium complexes having the general
formula [Ru(S)2(K)], where S = 2,2′-bipyridine/ 1,10-
phenanthroline and K = hfc, itsz, Meo-btsz, 4-Cl-btsz etc.,
1
National Institute for Science and Technology on Innovation on
Neglected Diseases (INCT/IDN), Center for Technological
Development in Health (CDTS), Fundação Oswaldo Cruz -
Ministério da Saúde, Av. Brazil 4036–Prédio da Expansão, 8°
Andar—Sala 814, Manguinhos, Rio de Janeiro 21040-361 RJ,
Brazil
reported (Karki et al., 2007). Complex [Ru (Phen)2
2+
(p-MOPIP)]
can effectively inhibit the proliferation of
Hep G-2 cell line with low IC50 value (7.2–1.3 µM)
(Schatzschneider et al., 2008), [Ru(Phen)2 (DBHIP)]2+ can
effectively induce apoptosis of BEL-7402 cell lines (Liu
et al., 2010). In recent year, several ruthenium-based com-
plexes have been investigated such as chiral ruthenium
complex [(1s, 2s)-DEPN]–RuCl2(PPh3)2 (Liu et al., 2010),
2
3
Programa de Desenvolvimento de Fármacos, Instituto de Ciências
Biomédicas, Universidade Federal do Rio de Janeiro, Rio de
Janeiro, RJ, Brazil
S. R. College of Pharmacy, Department of Pharmaceutical
Chemistry & Toxicology, Ananthasagar, Warangal 506371
Telangana, India
new
chiral—bridged
diamine/diphosphine
Ru(II)

Med Chem Res
complexes (Cui et al., 2010) RuCl2 (PPh3)N-b-bis(2-(di-
o-tolylphosphino)–benzyl] cyclohexane -1,2-diamine,
(1,4,7,10,13–penta thio cyclo pentadecane) chloro ruthe-
nium (II) hexa fluoro phosphate (Janzen et al., 2010),
pyridyl-based liquid supported ruthenium complex (Mei-
Ran et al., 2009), [Ru(bpy)Br)2 (acac)] (PF6) (Viala and
Bonvoisin, 2010), antiviral activity of ruthenium(II) arene
complexes (Allardyce et al., 2003). Recently we reported
Ru(II) complexes with pyrazoline ligands as anticancer
activity (Thota et al., 2012). In this report, we evaluated the
complexes type [Ru(R)2(K)]2+, (where R = 1,10-phenan-
throline/2,2′-bipyridyl and K = acetyl coumarin-inh, pyr-
azole-tch, acetyl coumarin-tsz, for anticancer activities. The
in vitro cytotoxic and activitiy of the complexes measure-
ment against the human cancer T-lymphocyte cell lines.
ruthenium trichloride with 1,10–phenanthrolene/2,2′-bipyr-
idyl. The final ruthenium complexes were synthesized by
treating [Ru(phen)2Cl2] with phenyl thiosemicarbazone
ligands to offered the corresponded complex.
Synthesis
General procedure for preparing [Ru(R)2(K)Cl2] (where
R = 2,2′-bipyridine/ 1,10-phenanthroline; K = acetyl cou-
marin-inh, pyrazole-tch, acetyl coumarin-tsz To the
black microcrystalline cis-bis(R)dichlororuthenium(II){cis-
Ru(R)2Cl2}(2 mmol) excess of ligand B (2.5 mmol) was
added and refluxed in anhydrous ethanol under nitrogen.
The initial colored solution slowly changed to brownish
orange at the end of the reaction, which was verified by thin
layer chromatography on silica plates. Then excess ethanol
was distilled off and silicagel (60–120 mesh) added to this
solution. The final complex was purified by column chro-
matography by using silica gel as stationary phase and
chloroform–methanol as mobile phase.
Experimental
Materials for synthesis
All reagents and solvents were purchased from Sigma-
Aldrich and used as received. The RuCl3.3H2O was pur-
chased from Sigma-Aldrich. All the melting points were
determined in open capillary and are uncorrected. ultra
violet–visible (UV-Vis) spectra were on a Jasco spectro-
photometer. Fourier transform infrared (FTIR) spectra were
recorded in KBr powder on a Jasco V410 FTIR spectro-
Characterization of synthesized Ru(II) complexes Ru-1:
[Ru(phen)2(ACINH)]Cl2, 52 %, black crystals; IR (KBr)
νmax: 3336 (N–H), 3014 (C–H), 2913 (C–H), 1680 (C=O)
1
cm−1. H-NMR (DMSO-d6, 400 MHz): δ = 9.26 (1H, s),
8.94 (1H, s), 8.89 (1H, s), 8.70 (2H, d), 8.58 (2H, d, J = 4.9
Hz), 8.42–8.31(2H, d, J = 5.0 Hz), 8.23 (1H, s), 8.11 (1H,
s), 7.98 (1H, s, NH), 7.83 (4H, m), 7.68–7.58 (4H, m) 7.54
(2H, dd) 7.42 (1H, s), 6.94 (2H, d), 6.52 (1H, s), 2.22 (3H,
CH3). 13C-NMR (DMSO-d6): 159.2 (s, 1C, C=O), 153.8
(s, 1C, C=O), 152.1(s, 1C), 149.4 (s, 1C), 149.0 (s, 1C),
148.8 (s, 1C), 148.4 (s, 1C), 148.0 (s, 1C), 147.4 (s, 1C),
147.2 (s, 1C), 146.8 (s, 1C), 146.4 (s, 1C), 143.6 (s, 1C),
138.4 (s, 1C), 137.8 (s, 1C), 137.6 (s, 1C), 137.2 (s, 1C),
136.4 (s, 1C), 133.8 (s, 1C), 129.8 (s, 1C), 129.4 (s, 1C),
129.2 (s, 1C), 129.0 (s, 1C), 127.8 (s, 1C), 127.6 (s, 1C),
127.2 (s, 1C), 127.0 (s, 1C), 126.4 (s, 1C), 125.8 (s, 1C),
125.2 (s, 1C), 125.0 (s, 1C), 124.6 (s, 1C), 124.2 (s, 1C),
123.8 (s, 1C), 123.2 (s, 1C), 122.4 (s, 1C), 122.0 (s, 1C),
120.8 (s, 1C), 119.4 (s, 1C), 119.0 (s, 1C) 4.9 (s, 1C, CH3).
FAB-MS (mNBA): 768 [Ru(phen)2 (ACINH)]2+, 461
[Ru(phen)2], 307 [ACINH]. Anal. Calcd. for C41H29Cl2
N7O3Ru1: C, 58.64; H, 3.45; N, 11.68. Found: C, 58.52;
1
meter by diffuse reflectance technique. H NMR spectra
were measured in CDCl3 and DMSO-d6 on a Bruker
Ultraspec AMX 400 MHz/300 MHz spectrometer. The
reported chemical shifts were against that of tetra-
methylsilane. FAB-mass spectra were recorded on a JEOL
JMS600 spectrometer with 3-nitro benzyl alcohol as matrix.
Microanalyses were carried out on an Elementar Vario
elemental analyzer.
The ruthenium compounds Ru-1–Ru-6 were prepared
using the synthetic strategy describes (Schemes 4 and 5).
The synthesis began by preparation of thiosemicabzone,
isonicotinyl hydrazones, and pyrazole thiocarbohydrazide
ligands (Schemes 1–3). The ligands were prepared accord-
ing to the published procedures. (de Oliveira et al., 2008).
The next step was performed by commercially available
Scheme 1 Synthesis of acetyl coumarin isonicotinyl hydrazone (ACINH)

Med Chem Res
Scheme 2 Synthesis of pyrazole thicarbohydrazides (PTCH)
Scheme 3 Synthesis of acetyl coumarin thiosemicarbazone (ACTSZ)
H, 3.44; N, 11.56. Ru-2: [Ru(bpy)2(ACINH)]Cl2, 48 %,
black crystals; IR (KBr) νmax: 3298 (N–H), 3094 (C–H)
2936 (C–H), 1680 (C=O) cm−1. 1H-NMR (DMSO-d6, 400
MHz): δ ppm: 9.18 (1H, s), 9.12 (1H, s), 9.08 (1H, s), 8.98
(1H, s), 8.86 (1H, s), 8.68 (2H, d), 8.54 (2H, d), 8.38–8.32
(2H, d, J = 5.0 Hz), 8.24–8.22 (2H, dd), 8.02 (1H, s, NH),
7.92 (3H, t), 7.66 (2H, d, J = 14.2 Hz), 7.54–7.48 (3H, m)
7.36 (2H, dd) 7.14 (2H, d), 2.24 (3H, CH3). 13C-NMR
(DMSO-d6): 159.2 (s, 1C, C=O), 153.8 (s, 1C, C=O),
152.1(s, 1C), 149.4 (s, 1C), 149.0 (s, 1C), 148.8 (s, 1C),
148.4 (s, 1C), 148.0 (s, 1C), 147.4 (s, 1C), 147.2 (s, 1C),
146.8 (s, 1C), 146.4 (s, 1C), 143.6 (s, 1C), 138.4 (s, 1C),
137.8 (s, 1C), 137.6 (s, 1C), 137.2 (s, 1C), 136.4 (s, 1C),
133.8 (s, 1C), 129.8 (s, 1C), 129.4 (s, 1C), 129.2 (s, 1C),
129.0 (s, 1C), 127.8 (s, 1C), 126.6 (s, 1C), 125.8 (s, 1C),
125.2 (s, 1C), 124.0 (s, 1C), 123.6 (s, 1C), 123.4 (s, 1C),
123.0 (s, 1C), 121.6 (s, 1C), 121.4 (s, 1C), 120.2 (s, 1C),
118.8 (s, 1C), 118.6 (s, 1C) 4.9 (s, 1C, CH3). FAB-MS
(mNBA): 791 [Ru(bpy)2 (ACINH)]2+(Cl2)−; 720 [Ru(bpy)2
(ACINH)]2+; 413 [Ru(bpy)2]; 307 [ACINH]. Anal. Calcd.
for C37H29Cl2N7O3Ru1: C, 56.14; H, 3.67; N, 12.39.
Found: C, 56.08; H, 3.62; N, 12.28. Ru-3: [Ru
(phen)2(PTCH)]Cl2, 44 %, black crystals; IR (KBr) νmax:
3462 (NH2), 3268 (N–H) 2982 (C–H), 1328 (C=S) cm−1.
1H NMR (DMSO-d6, 400 MHz): δ = 9.28 (1H, s), 8.96 (1H,
s), 8.88 (1H, s), 8.80 (1H, s, J = 4.9 Hz), 8.62 (2H, d, J =
8.4 Hz), 8.48 (2H, d), 8.36 (2H, d), 7.94 (2H, d, J = 5.0 Hz),
7.86 (3H, m), 7.58 (2H, d), 7.32 (1H, s), 7.28 (2H, d, J =
14.6 Hz), 7.15 (1H, s), 6.95 (1H, s), 6.51–6.44 (2H, d) 6.25
(1H, s). FAB-MS (mNBA): 715 [Ru(phen)2 (PTCH)]2+
(Cl2)−; 644 [Ru(phen)2 (PTCH)]2+; 461 [Ru(phen)2]; 183
[PTCH]. Anal. Calcd. for C30H25Cl2N9Ru1S1: C, 50.35; H,
3.49; N, 17.62. Found: C, 50.26; H, 3.42; N, 17.64. Ru-4:
[Ru(bpy)2(PTCH)]Cl2, 54 %, black crystals; IR (KBr)
νmax: 3480 (NH2), 3294 (N–H) 2976 (C–H), 1332 (C=S)
8.64–8.44 (2H, d, J = 8.4 Hz), 8.40–8.28 (2H, d), 8.12 (3H,
d), 7.82 (2H, d, J = 4.9 Hz), 7.82–7.64 (4H, m), 7.46 (1H,
s), 7.34 (2H, d, J = 14.8 Hz), 7.08 (1H, s), 6.98 (1H, s),
6.76–6.52 (2H, d) 6.18 (1H, s). FAB-MS (mNBA): 667
[Ru(bpy)2 (PTCH)]2+(Cl2)−; 596 [Ru(bpy)2 (PTCH)]2+;
413 [Ru(bpy)2]; 183 [PTCH]. Anal. Calcd. for
C26H25Cl2N9Ru1S1: C, 46.77; H, 3.75; N, 18.89. Found: C,
46.68; H, 3.66; N, 18.78. Ru-5: [Ru(phen)2(ACTSZ)]Cl2,
46 %, black crystals; IR (KBr) νmax: 3421 (NH2), 3255
1
(N–H) 2986 (C–H), 1678 (C=O), 1334 (C=S) cm−1. H
NMR (DMSO-d6, 400 MHz): δ ppm = 9.32 (1H, s), 9.18
(1H, s), 9.02 (1H, s), 8.94 (1H, s, J = 4.9 Hz), 8.72 (2H, d, J
= 8.4 Hz), 8.64 (2H, d), 8.44 (2H, d), 8.32 (2H, d, J = 5.0
Hz), 8.16 (2H, d), 8.04 (2H, d), 7.98-7.68 (4H, m), 7.36
(2H, d), 7.22 (2H, d, J = 14.6 Hz) 2.24 (3H, s). 13C-NMR
(DMSO-d6): 179.6 (s, 1C, C=S), 165.42 (s, 1C, C=O),
149.8 (s, 1C), 149.6 (s, 1C), 149.2 (s, 1C), 149.0 (s, 1C),
148.6 (s, 1C), 148.4 (s, 1C), 147.8 (s, 1C), 147.2 (s, 1C),
142.4 (s, 1C), 137.2 (s, 1C), 136.8 (s, 1C), 136.6 (s, 1C),
136.2 (s, 1C), 135.6 (s, 1C), 134.8 (s, 1C), 129.4 (s, 1C),
128.8 (s, 1C), 128.2 (s, 1C), 128.0 (s, 1C), 127.4 (s, 1C),
127.0 (s, 1C), 126.8 (s, 1C), 126.4 (s, 1C), 125.2 (s, 1C),
125.0 (s, 1C), 124.8 (s, 1C), 124.4 (s, 1C), 124.2 (s, 1C),
123.0 (s, 1C), 122.8 (s, 1C), 122.6 (s, 1C), 121.6 (s, 1C),
119.8 (s, 1C) 4.9 (s, 1C, CH3). FAB-MS (mNBA): 793 [Ru
(phen)2 (ACTSZ)]2+(Cl2)−; 722 [Ru(phen)2 (ACTSZ)]2+;
461 [Ru(phen)2]; 261 [ACTSZ]. Anal. Calcd. for
C36H27Cl2N7 O2Ru1S1: C, 54.47; H, 3.41; N, 12.36. Found:
C, 54.42; H, 3.29; N, 12.24. Ru-6: [Ru(bpy)2(ACTSZ)]
Cl2, 61 %, black crystals; IR (KBr) νmax: 3442 (NH2), 3288
1
(N–H) 2924 (C–H), 1678 (C=O), 1334 (C=S) cm−1.. H
NMR (DMSO-d6, 400 MHz ): δ ppm: 9.14 (1H, s), 9.06
(1H, s), 8.92 (1H, s), 8.88 (1H, s, J = 5.0 Hz), 8.82 (2H, d, J
= 8.4 Hz), 8.58 (2H, d), 8.46 (2H, d), 8.28 (2H, d, J = 5.0
Hz), 8.12 (2H, d), 8.01–7.98 (3H, m), 7.90–7.66 (4H, m),
7.24 (1H, s), 7.18 (2H, d, J = 14.6 Hz) 2.16 (3H, s). 13C-
NMR (DMSO-d6): 180.2 (s, 1C, C=S), 164.8 (s, 1C, C=O),
1
cm−1. H NMR (DMSO-d6, 400 MHz): δ = 9.04 (1H, s),
8.92 (1H, s), 8.82 (1H, s), 8.76 (1H, s, J = 4.9 Hz,),

Med Chem Res
150.6 (s, 1C), 150.4 (s, 1C), 149.8 (s, 1C), 149.6 (s, 1C),
149.4 (s, 1C), 148.8 (s, 1C), 148.6 (s, 1C), 148.4 (s,
1C), 142.6 (s, 1C), 137.4 (s, 1C), 137.2 (s, 1C), 136.6
(s, 1C), 136.0 (s, 1C), 129.8 (s, 1C), 129.4 (s, 1C), 128.8 (s,
1C), 128.6 (s, 1C), 127.0 (s, 1C), 126.6 (s, 1C), 126.2
(s, 1C), 125.4 (s, 1C), 124.6 (s, 1C), 124.0 (s, 1C), 123.8 (s,
1C), 122.4 (s, 1C), 121.8 (s, 1C), 119.0 (s, 1C) 5.2 (s, 1C,
CH3). FAB-MS (mNBA): 745 [Ru(bpy)2 (ACTSZ)]2+(Cl2)−
the synthesis of complexes. The product cis-bis(1,10-phe-
nanthroline/2,2′-bipyridine)dichlororuthenate(II) was then
refluxed in ethanol in presence of nitrogen with various
ligands to yield the final octahedral ruthenium complexes.
In this homoleptic chelate the first two ligands to enter the
complex in a stepwise assembly were 1,10-phenanthroline/
2,2′-bipyridine molecule, respectively. Since both the
ligands are same, so a single step method was adopted
for its synthesis. Ruthenium trichloride was refluxed in
DMF in the presence of 1,10-phenanthroline/2,2′-bipyr-
idine, in excess of the stoichiometric amount, which
afforded the final product cis-bis (1,10-phenanthroline)
;
674 [Ru(bpy)2 (ACTSZ)]2+; 413 [Ru(bpy)2]; 261
[ACTSZ]. Anal. Calcd. for C32H27Cl2N7Ru1S1: C, 51.54;
H, 3.63; N, 13.15. Found: C, 51.48; H, 3.57; N, 13.08.
dichlororuthenium(II)/cis-bis(2,2′-bipyridine)
dichloror-
uthenium(II) (Scheme 4). The introduction of the third
ligand was carried out in the presence of alcohol in the
presence of nitrogen atmosphere (Scheme 5). The final
chelate formed had ionic chloride in the molecule.
Results and discussion
Chemistry
The compounds of the newly synthesized ruthenium
compounds were confirmed by UV-Vis, FTIR, H-NMR,
Ruthenium trichloride undergoes reduction when refluxed
in dimethyl formamide (DMF). So when refluxed along
with two-fold molar ratios of the bidentate ligand (1,
10-phenanthroline/2,2′-bipyridine), a homoleptic complex
is formed. The product cis-bis(1,10-phenanthroline/2,2′-
bipyridine)dichlororuthenate(II) is the starting material for
1
13C-NMR, mass spectroscopy and elemental analysis. In the
UV-Vis spectra, all the ruthenium compounds showed
broad and intense visible bands between 320 and 520 nm
due to metal to ligand charge transfer transition. In the UV
region, the bands at 280 and 320 nm were assigned to 1,10-
phenanthroline ligand π–π*charge transfer transitions. The
IR spectras contained the absorption bands revealing the
1
existence of the NH2, NH, C=S, and C=O gps. The H-
NMR spectra of the complex, [Ru(phen)2(ACINH]Cl2
shown 29 resonance peaks (δ 9.34–2.12). The mass spectra
of the Complex Ru-1 gave the anticipated molecular ion
peak and main fragmentation peaks, which were in accor-
dance with the title complexes. The in vitro antineoplastic
Scheme 4 Synthesis of cis-[Ru(R)2Cl2] where R = 1, 10-Phenan-
throline/ 2,2′-bipyridyl
Scheme 5 Synthesis of tris
chelates from cis-[Ru(R)2Cl2]

Med Chem Res
Table 1 Cytotoxic studies of ruthenium complexes
a
Comp. code
IC50 (µmol/L)
CEM
L1210
Molt 4/C8
HL60
BEL7402
ACINH
PTCH
ACTSZ
Ru-1
110
8
224 28
140 65
148 52
230 72
158 46
126 24
192 48
116 25
228 14
154 46
98 40
96 34
108 12
116 12
0.98 0.04
1.2 0.4
0.92 0.6
1.6 0.02
0.92 0.8
Ru-2
1.4 0.6
1.8 0.2
2.5 0.25
0.96 0.04
1.2 0.02
0.44 0.04
0.64 0.6
0.87 0.06
0.98 0.04
0.68 0.04
0.76 0.08
0.84 0.6
1.26 0.4
0.92 0.06
1.4 0.6
Ru-3
0.64 0.06
0.76 0.08
0.34 0.04
0.48 0.06
0.51 0.1
0.82 0.02
0.49 0.25
0.28 0.2
0.45 0.25
1.2 0.02
Ru-4
Ru-5
0.66 0.24
0.84 0.06
0.78 0.04
Ru-6
0.92 0.04
0.98 0.02
Cisplatin
a
50 % inhibitory concentration, required to inhibit tumor cell proliferation by 50 %
Compliance with ethical standards
activities of the synthesized complexes against the human
cancer T-lymphocyte cell lines molt 4/C8 and CEM and the
murine tumor leukemia cell lines L1210, human oral epi-
dermoid carcinoma KB cells, human promyelocytic leuke-
mia cells (HL60), and Bel-7402 liver cancer cells were
evaluated by the standard MTT assay. (Thota et al., 2009).
As described in Table 1, complexes Ru-3, Ru-4, Ru-5 &
Ru-6 exhibit very potent antineoplastic activity against all
the cell lines, especially Ru-5 & Ru-6 shown very potent
antitumor activity than cisplatin and shows good selectivity.
On comparison to ruthenium compounds, the ligands dis-
played the cytotoxicity at higher concentration. Thus, the
ruthenium compounds proved inhibitory to tumor growth at
submicromolar concentration.
Conflict of interest The authors declare that they have no conflict of
interests.
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Conclusion
In summary, we described the synthesis of novel Ru(II)
complexes bearing ACINH, PTCH, and ACTSZ deriva-
tives. From the results presented in Table 1, it is clear that
several ruthenium compounds exhibited a marked inhibi-
tory effect on the proliferation of tumor cells. Thus, the
ruthenium compounds proved inhibitory to tumor growth at
submicromolar concentration. Their ligands, however, were
not antitumorally active. Nevertheless, further translational
development of low molecular weight bifunctional Ru(II)
−arene complexes are worthwhile as their low toxicity is
attractive for development of future anticancer therapies.
Acknowledgments This work was supported by National Council
for Scientific and Technological Development (CNPq), Coordenação
de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Oswaldo
Cruz Foundation (Fiocruz), and Department of Science and Technol-
ogy, New Delhi, India (No. SR/WOS-A/LS-562/2011, dated 27 March
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