A monomeric complex of ZnII with ornidazole [Zn(Onz)2Cl2] decreases formation of the nitro-radical anion (R–NO2˙−), and this is realized by recording it in an enzyme assay using xanthine oxidase, which is a model nitro-reductase.
The current-voltage characteristics of bilayer lipid membranes of oxidized cholesterol separating two bathing solutions have already been extensively studied under a DC electric field. The observed deviation from linearity at high field has been explained by field-induced pore formation, which then act as ion channels in the membrane. Using thin films of oxidized cholesterol and of dipalmitoyl phosphatidylcholine, we have reported for the first time similar deviation from nonlinearity in the DC I-V characteristics when the applied field is above 40 V/cm. Upon application of an AC field, the conductivity increases as square of frequency, while the nonlinear nature of the I-V characteristic curve is still retained at all frequencies up to 5,000 Hz. Our results indicate that besides pore formation, the intrinsic electrical properties of the constituent lipid molecules are also responsible for the observed nonlinearity.
A family of three
water-soluble half-sandwich arene–ruthenium
complexes, depicted as C
1
–C
3
, having the general formula [Ru(p-cymene)(L)Cl]Cl has been synthesized, where L represents
(1H-benzo[d]imidazol-2-yl)guanidine
(L
1
) or (benzo[d]oxazol-2-yl)guanidine (L
2
)
or (benzo[d]thiazol-2-yl)guanidine (L
3
). The crystal structure of complex C
3
has been determined. The complexes
show several absorption bands in the visible and ultraviolet regions,
and they also show prominent emission in the visible region while
excited near 400 nm. Studies on the interaction of ligands L
1
–L
3
and complexes C
1
–C
3
with calf thymus DNA reveal that
the complexes are better DNA binders than the ligands, which is attributable
to the imposed planarity of the ruthenium-bound guanidine-based ligand,
enabling it to serve as a better intercalator. Molecular docking studies
show that the complexes effectively bind with DNA through electrostatic
and H-bonding interactions and partial intercalation of the guanidine-based
ligands. Cytotoxicity studies carried out on two carcinoma cell lines
(PC3 and A549) and on two non-cancer cell lines (BPH1 and WI-38) show
a marked improvement in antitumor activity owing to complex formation,
which is attributed to improvement in cellular uptake on complex formation.
The C
1
complex is found to exhibit
the most prominent activity against the PC3 cell line. Inclusion of
the guanidine-based ligands in the half-sandwich ruthenium–arene
complexes is found to be effective for displaying selective cytotoxicity
to cancer cells and also for convenient tracing of the complexes in
cells due to their prominent emissive nature.
Formation of nitro radical anion (−NO 2 •− ) and other reduction products of 5-nitroimidazoles, although important for antimicrobial activity, makes the drugs neurotoxic. Hence, an appropriate generation and their role in the free radical pathway needs proper realization. This was attempted by studying the action of tinidazole and its Cu II complexes on model targets (nucleic acid bases and calf thymus DNA). Results obtained were correlated with studies on biological species where prevention of biofilm formation on Staphylococcus aureus and Pseudomonas aeruginosa was followed. Tinidazole and its Cu II complexes subjected to electrochemical reduction in aqueous solution, under de-aerated conditions, interact with model nucleic acid bases and calf thymus DNA. These model targets were followed to realize what happens when such compounds undergo enzymatic reduction within cells of microorganisms that they eventually kill. Studies reveal that Cu II complexes were better in modifying nucleic acid bases and calf thymus DNA than tinidazole; damage caused to nucleic acid bases was correlated with that caused to DNA, indicating that compounds affect DNA rich in thymine and adenine. Minimum bactericidal concentrations on sessile S. aureus and P. aeruginosa for the monomeric Cu II complex were 12.5 and 20.25 μM respectively, while those for the dimeric complex were 40.0 and 45.0 μM, respectively. Biofilm formation by P. aeruginosa and S. aureus and viability count of sessile cells were also determined. Cu II complexes of tinidazole brought about substantial reduction in carbohydrate and protein content in S. aureus and P. aeruginosa. Downregulation of quorum sensing signaling mechanism viz. reduced production of pyocyanin and elastase during biofilm formation was also detected. Cu II complexes showed much higher tendency to prevent biofilm formation than tinidazole, almost comparable to amoxicillin, an established drug in this regard.
The
treatment of malignant cells that are deficient in oxygen due
to the insufficient flow of blood is often seen as a major hindrance
in radiotherapy. Such cells become radio-resistant because molecular
oxygen, the natural and best radio-sensitizer, is depleted. Hence,
to compensate this deficiency in oxygen, there is a need for agents
that enhance radiation-induced damage of cells (radio-sensitizers)
in a manner that normal cells are least affected. Simultaneously,
agents capable of showing activity under hypoxic conditions are known
as hypoxic cytotoxins that selectively and preferably destroy cells
under hypoxic environments. 5-Nitroimidazoles fit both definitions.
Their efficiency is based on their ability to generate the nitro radical
anion that interacts with the strands of DNA within cells, either
damaging or modifying them, leading to cell death. 5-Nitroimidazoles
are important radio-pharmaceuticals (radio-sensitizers) in cancer-related
treatments where the nitro radical anion has an important role. Since
its generation leads to neurotoxic side effects that may be controlled
through metal complex formation, this study looks at the possibility
of two monomeric complexes of Ornidazole [1-chloro-3-(2-methyl-5-nitro-1
H
-imidazole-1-yl)propan-2-ol] with Cu
II
and Zn
II
to be better radio-sensitizers and/or hypoxic cytotoxins
than Ornidazole. The study reveals that although there is a decrease
in nitro radical anion formation by complexes, such a decrease does
not hamper their radio-sensitizing ability. Nucleic acid bases (thymine,
cytosine, and adenine) or calf thymus DNA used as targets were irradiated
with
60
Co γ rays either in the absence or presence
of Ornidazole and its monomeric complexes. Radiation-induced damage
of nucleic acid bases was followed by high-performance liquid chromatography
(HPLC), and modification of calf thymus DNA was followed by ethidium
bromide fluorescence. Studies indicate that the complexes were better
in performance than Ornidazole. Cu
II
-ornidazole was significantly
better than either Ornidazole or Zn
II
-ornidazole, which
is attributed to certain special features of the Cu
II
complex;
aspects like having a stable lower oxidation state enable it to participate
in Fenton reactions that actively influence radio-sensitization and
the ability of the complex to bind effectively to DNA.
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