metal complexes presentation ruthenium based- Copy.pptx

1. • Radiophysical properties of Ru can be applied to radiodiagnostic imaging
• Immunosuppressants
• Antimicrobials (against malaria and Chaga´s disease)
• Antibiotics (against Salmonella typhi and Enterobacteria faecalis
• Nitrosyl delivery/scavenger tools
• Vasodilator/vasoconstrictor agents
• Cancer
Chemotherapy
 Ruthenium compounds are known to be less toxic and no
cross resistant than platinum counterpart.
Ruthenium has a range of oxidation state (II,III and IV)
accessible under physiological Condition, which is unique
among the platinum-group metals.
Ruthenium based complexes as Anticancer agent

2. Ru(II) and Ru(III) complexes
• Among the best studied non-platinum metal complexes with
anticancer activity.
• Ru complexes have DNA binding properties similar to
Pt complexes.
• Ru(III) are characterized by a high affinity to serum proteins –
crucial for drug accumulation into the tumor tissue.
• Besides GSH, Ru(III) complexes also interact with NO˙ known as
intracellular and intercellular messenger for diverse physiological
processes.

3. Cancer cells need considerably more energy than healthy cells. Their metabolism
runs at full speed and requires large amounts of micronutrients, particularly iron.
Cancer cells
Ruthenium
Ruthenium have the ability to bind albumin and transferrin And because cancer
cells need more Iron, transferrin receptors are over expressed, Thereby allowing
ruthenium-based drugs to be more efficiently delivered to cancer cells.

4. Clinically evaluated ruthenium-based anticancer drugs
Ruthenium complexes with anticancer properties
• NAMI-A binds strongly to serum proteins, including the iron transporter
transferrin and it induces cell arrest in the premitotic G (2)-M phase.
• KP1019 drug induce cell death and have a significant cytotoxicity in vitro
against colorectal cell lines SW480 and HT29. This drug was also found to be
highly effective in in vivo tests and it induces apoptosis in colorectal cell lines
mainly via the intrinsic mitochondria apoptosis pathway.

5. Strategy to tether Organometallic ruthenium arene anticancer
compounds to recombinant Human Serum Albumin
 The main role of Human serum albumin (HSA) is to maintain
the osmotic pressure in the blood and to scavenge free radicals as
an antioxidant.
 HSA is known to accumulate in tumors.
 The carrier conjugate of various organic anticancer drugs such
as chlorambucil, doxorubicin, and paclitaxel.
RAPTA: 1,3,5-triaza-7-
phosphatricyclo[3.3.1.1]
- decane ligand

6. Copper based complexes as Anticancer agent
1. Anticancer copper complexes can be classified into
two major groups; copper chelators and copper ionophores.
2. Copper chelators suitable copper ions from cells inside the body
and thus aim to limit cancer development by inquisitive with
increase and malignant processes.
3. On the other hand, copper ionophores carrying copper into cells
growing intracellular levels and applying cytotoxic
consequences through a numerous of passageways.

7. 4. Many copper ionophores liberate coordinated copper below the
reductive intracellular environment, allocating copper to become
bioavailable and such compounds are generally more capable at killing
cancer cells.
5. The common oxidation states of copper are +1 and +2, although
copper(I) compounds are generally unstable towards oxidation to the
copper(II) form and are less studied as anticancer compounds.
6. The ability of copper to undergo facile cycling between +1 and +2
oxidation states enables it to serve as a catalytic center in many redox
enzymes.
7. Generally, copper(II) complexes, being redox active, stimulate the
production of reactive oxygen species that cause DNA damage in cancer
cells.

8. Copper(II) complexes of Semicarbazones
• Micarbazone
• Copper(II) salicylaldehyde semicarbazone complexes that show
anti-tumor activity against the human breast cancer cell line
MCF7 (1a & 1b)
• The activity of these complexes was attributed to their ability to
generate considerable intracellular oxidative stress via the
Cu2+/Cu+ redox couple.

9. • Macrocyclic ligands offer the advantage of forming
metal complexes that are relatively stable under
physiological conditions.
• They can also be readily functionalized
with groups that confer water
solubility and/or interaction with
biomolecules such as DNA.
• Copper(II) complex of 2,2,2´,2´-S,S-
[bis(bis-N,N-2- thiobenzimidazolyloxalato
-1,2-ethane)] (as shown in Figure) binds
to DNA through partial intercalation,
and that it possesses excellent DNA cleavage activity .
Copper(II) complexes of Macrocyclic ligands

10. Copper(II) complexes of Biomolecules &
their derivatives
• The biocompatibility of biomolecules, most of
which contain donor atoms, makes them
attractive candidates as ligands for copper-based
pharmaceuticals.
• Furthermore, since biomolecules are the natural
substrates of enzymes, their structurally similar
metal complexes can potentially act as
competitive inhibitors and, hence, disrupt key
metabolic pathways in cancer cells.
• Copper complexes of l-glutamine Schiff bases
have also been reported to have significant
proteasome-inhibitory activity in human breast
cancer and leukemia cells.