ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 1, pp. 154–160. © Pleiades Publishing, Ltd., 2016.
154
Octahedral Titanium(IV) Complexes with Five Novel Hydroximic
Acid Ligands: Synthesis, Spectroscopic Characterization,
and in vitro Activities on IMR-32 and CHO Cell Lines
and Ten Bacterial Strains
1
Sheetal
a
, K. Nehra
b
, R. Kaushal
c
, S. Arora
d
, D. Kaur
d
, and R. Kaushal
a
a
Department of Chemistry, National Institute of Technology, Hamirpur, Himachal Pradesh, 177005 India
b
Department of Biotechnology, Deenbandhu Chhotu Ram University of Science and Technology,
Murthal 131039, Sonepat (Haryana), India
c
Department of Parasitology, PGIMER, Chandigarh 160012 India
d
Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005 India
e-mail: kaushalraj384@gmail.com
Received June 25, 2015
Abstract—Complexes with the composition TiCl
4
L
2
where L = benzohydroxamic acid, 2-hydroxybenzo-
hydroxamic acid, acetohydroxamic acid, hydroxyurea, and N-hydroxy-N-phenylbenzamide have been
synthesized by reaction of titanium tetrachloride with 2 equiv of the corresponding hydroxamic acids. The
structure of these complexes has been studied by analytical and spectroscopic (FT-IR, UV-Vis, MS,
1
H and
13
C
NMR) techniques. The free ligands and the complexes have been tested in vitro to evaluate their activities
against IMR-32 (neuroblastoma) cancer cell line, CHO p-40 (Chinese hamster ovary) normal cells, and ten
pathogenic bacterial strains.
Keywords: Titanium, hydroxamic acid, spectroscopy, anticancer and antibacterial activity
1
The text was submitted by the authors in English.
After the discovery of first hydroxamic acid by
Lossen, much attention has been given to biological
application of hydroximates due to their ability to
inhibit a variety of enzymes, including ureases,
peroxidases, and matrix metalloproteinases [1–4]. In
medicinal applications, hydroxamic acid moieties are
used in the design of therapeutics targeting
cardiovascular diseases, insecticides, and antimicrobial
agents [5–8]. Hydroxamic acids are usually used as
supporting ligands in chemistry and biology because of
their tautomerism and potential chelating properties [9,
10]. Generally, tautomers of hydroxamic acid may
have different conformations or configurations [11],
but they prefer Z-hydroxamic acid structure as shown
in Scheme 1. The principal coordination mode
observed in metal–hydroxamic acid complexes
involves oxygen and nitrogen atoms, and the ligand
has either one (hydroxamic) or two hydroxy groups
(hydroximic) [12].
In the field of cancer treatment, cisplatin and many
other platinum-based drugs, namely carboplatin,
oxaliplatin, tetraplatin, and satraplatin [13], as well as
non-platinum based drugs such as budotitane,
titanocene dichloride [14], NAMI-A, KP1019 [15],
and auranofin [16], have shown remarkable results.
Among these non-platinum anticancer drugs,
budotitane and titanocene dichloride were the first
metal-based chemotherapeutics that reached Phase I
clinical trials. Although both complexes showed
promise in these preliminary studies, budotitane has
not progressed past Phase I due to formulation
problems, and titanocene dichloride has not progressed
beyond Phase II due to its low efficacy versus toxicity
ratio [17]. These difficulties have spurred the
development of titanium complexes that display higher
potency and hydrolytic stability. The structures of
some clinically used titanium and ruthenium based
anticancer drugs are shown in Scheme 2.
In this work we have systematically studied tita-
nium(IV) complexes with different hydroxamic acid
DOI: 10.1134/S1070363216010242