The serendipitous discovery by Rosenberg in 1965 of the anti-proliferative activity of a platinum complex, recognized as cis-diamminedichloroplatinum (cisplatin) and its subsequent success-full introduction in the therapy of testicular cancer (1978), fostered a renewed and growing interest in metal-based drugs, particularly organometallic complexes, as antitumor agents. Indeed, a very impressively high cure-rate, was observed with cisplatin. Metals and their organometallic compounds : PLATINUM(Cisplatin, Carboplatin, Oxaliplatin) RUTHENIUM(KP418, KP1019, etc) GOLD(Auranofin, Tetrahedral gold complexes, Phosphol-containing gold complexes, etc) IRON(Ferrocene, Ferrocifen) COBALT(Hexacarbonyl dicobalt) GALLIUM(Gallium 8-quinolinonate[KP46], Gallium maltolate)

1. ORGANOMETALLIC
COMPOUNDS IN ONCOLOGY
IMPLICATIONS OF NOVEL PLATINUM COMPLEX COMPOUNDS AS
ANTITUMOR AGENTS
RANA SAHA, B.Pharm.,
NSHM Knowledge Campus , Kolkata

2. CANCER
Cancer is a group of diseases involving
abnormal cell growth with the potential to
invade or spread to other parts of the
body. These contrast with benign tumors,
which do not spread.
The major types of cancer are carcinoma,
sarcoma, melanoma, lymphoma, and
leukemia.
In metastasis, cancer cells break away
from where they first formed (primary
cancer), travel through the blood or lymph
system, and form new tumors (metastatic
tumors) in other parts of the body. The
metastatic tumor is the same type of
cancer as the primary tumor.

3. THE MOST
COMMON TYPES
OF CANCER IN
INDIA :
 India ranks 3 rd in
cancer cases after
China and the US.
 The most common
cancers in India are
breast cancer,
cervical cancer and
oral.

4. ANTICANCER DRUGS
The anticancer drugs either kill
cancer cells or modify their
growth.
Anticancer drugs are classified
imto two categories –
1) Drugs acting directly on the
cells (Cytotoxic drugs)
e.g. Alkylating agents,
antimetabolites, antibiotics,
novel organotins, etc.
2) Drugs altering hormonal
milieu
e.g. Glucocorticoids, estrogens,
GnRH analogues, etc.

5. IMPLICATIONS OF NOVEL ORGANOTINS AS
ANTITUMOR AGENT
Since the introduction of
cisplatin in cancer therapy, metal
complexes and organometallic
compounds have been gaining
growing importance in oncology.
The serendipitous discovery by
Rosenberg in 1965 of the anti-
proliferative activity of a
platinum complex, recognized as
cis-diamminedichloroplatinum
(cisplatin) and its subsequent
success-full introduction in the
therapy of testicular cancer
(1978), fostered a renewed and
growing interest in metal-based
drugs, particularly
organometallic complexes, as
antitumor agents.

6. METALS USED TO PREPARE NOVEL ORGANOTINS ACT AS
ANTITUMOUR DRUG
PLATINUM(Cisplatin, Carboplatin, Oxaliplatin)
RUTHENIUM(KP418, KP1019, etc)
GOLD(Auranofin, Tetrahedral gold complexes, Phosphol-containing gold
complexes, etc)
IRON(Ferrocene, Ferrocifen)
COBALT(Hexacarbonyl dicobalt)
GALLIUM(Gallium 8-quinolinonate[KP46], Gallium maltolate)

7. CISPLATIN
 Cisplatin is
among the
most active
anticancer
agents,
producing
DNA damage
similar to
alkylating
agents.

8. CISPLATIN AND OTHER
PLATINUM COMPLEXES IN
THE THERAPY OF CANCER
At present, cisplatin, carboplatin, and
oxaliplatin are the only metal-based
anticancer agents soundly established
in clinic and are found in a large
number (>50%) of chemotherapeutic
regimens
In an attempt to overcome the issue of
capturing and inactivation of the
complex by macromolecular blood
components and/or thiol-containing
reductants that might modulate the
sensitivity of cells to the drug, thus
novel PtII(as thioplatin and picoplatin )
and PtIV(as satraplatin and
ethacraplatin ) complexes have been
developed.

9. CISPLATIN : SITES FOR
PLATINUM BINDING -
Mitochondrial DNA, which is devoid
of histone proteins or NER (one of
the DNA repair systems), was found
to be a major target of cisplatin
Cisplatin is extensively used for the
treatment of testicular and ovarian
cancers and increasingly against
other types of solid tumors
(head/neck, lung, cervical, and
bladder). The cytotoxic effect of
cisplatin is thought to be due to
attack on DNA bases and induction
of apoptosis in cancer cells

10. CISPLATIN : WHY NOT
TRANSPLATIN ?
 On the interactions of cisplatin [cis-
diamminedichloroplatinum(II)] and
transplatin [trans-
diamminedichloroplatinum(II)] with two
model proteins, ubiquitin (Ub) and horse
heart myoglobin (Mb).
 When binding ubiquitin, Met1 is the
preferred binding site of cisplatin, but not
of transplatin.
 Cisplatin binds faster than transplatin to
both ubiquitin and horse heart
myoglobin.
 Rapid deactivation.
 27% clearance