Replace length at the imidazole moiety to promote

Replace the aliphatic
amine ligand with azathrioclides or aromatic amines, is another procedure to
enhance the cellular accumulation of cisplatin-related compounds. This approach
product Pt-compounds with good results specially when introduction of 7-azaindole halogen derivatives.

Ligands were synthesized under this
procedure by Muchova et al111. The ligands were investigated against ovarian
cancer and cisplatin sensitive cell line A2780, the results revealed that these
ligands were toxic to ovarian cancer and showed better IC50 values than
cisplatin-sensitive cell line A2780. Potential factors
that can be involved in the mechanism underlying the cytotoxic effects of these
compounds originate primarily from the cellular active accumulation. Other
examples of cisplatin N-heterocycle complexes have been reported by Steara et
al. 112 and ?akomska et al. 113 with the use of 1,2,4-triazole-1,5a
-pyrimidine and 7-azindol, respectively. The application and fate of these
complexes in biological systems are characterized by their water stability, the
thermodynamic aspects of their interactions with cysteine, and the reduction of
glutathione and human protein in the blood.

A series of Pt(II)
complexes with imidazole ligands prepared by Ferri et al 114. The complexes
were investigated against cancer cell line partially resistant to cisplatin but
sensitive to oxaliplatin. Containing of
these compounds on a heterocycle and an amine N-donor, maintain the aliphatic
amino function in order to display the best trans effect and display a chain of
appropriate length at the imidazole moiety to promote the lipophilicity.

A series of cisplatin-like
compounds with amino
phosphonate ester as the carrier ligand and chloride as the leaving group were prepared by Huang et al. 115,116, in order to increase the selectivity of the complexes as
anticancer drugs. To increase the solubility and to enhance transport through
the cell membrane introduction of a phosphate group for targeted delivery is
good strategy because alkaline phosphatase is overexpressed in the
extra-cellular space of specific tumor cells such as ovarian and carcinoma
cells. Moreover some phosphate groups have high affinity for calcium
ions and have been used to design targeted drugs for testament of bone cancer.

A cisplatin-like complex in which the two ammonia ligands are replaced by the
cyclindependent kinase inhibitor bohemine was prepared
by Novakova et al. 117. The complex
investigated against different cancer cell lines and showed a unique anticancer
profile which attributed to the mechanism of interaction with DNA which was
different from that of cisplatin.

The same group 118
synthesized Pt(II) complexes with disubstituted
and trisubstituted derivatives of the plant hormone kinetin as carrier
ligands. The complexes were investigated as
potential anticancer drugs against A2780cisR and A2780 cells, the experimental
results showed that the complexes were able to circumvent cisplatin resistance
in A2780cisR cells and more cytotoxic to A2780cells than cisplatin. This is
mainly due to stable degradation and interactions with glutathione and
guanosine monophosphates.

A series of dichloridoplatinum(II) complexes of podophyllotoxin were prepared
by Hui, Zhang and Chen 119. The complexes were investigated as anticancer
agents and the results revealed that the most potent cytotoxicity was appeared
by the complex in which
cis-4-O-(2-2-diaminopropanoyl)podophyllotoxindichloride-platin(II). This compound leads to the arrest of the cell cycle in the
G2 / M phase and prevents the formation of microtubes in the HeLa cells. In
addition, it has strong DNA division capabilities.

A series of chloride Pt(II) complexes of 2-hydroxy-3-(aminom
ethyl)-1,4-naphthoquinone were investigated by Neves
et al. 120. The complexes were tested as anticancer
agents against different cancer cells. All complexes showed high cytotoxicity
against cancer cell lines, the capability of quinone derivatives to form
reactive oxygen species enable them to have anticancer properties and extensively
studied in vivo as anticancer agents. The chemical and biophysical
properties of quinone ligands effected by PtCl2
complexes, this effected led to improvement of interaction of these complexes
with DNA and catalytically inhibit topoisomerase I.

Pages et al. 121 and
Garbutcheon-Singh et al. 122 synthesized numerous active complexes with the
general formula Pt(IL)AL)2+,where IL is an aromatic intercalating ligand and
AL is an ancillary ligand. The intercalating ligands included
1,10-phenanthrolinederivatives and dipyridoquinoxaline variants, whereas the
ancillary ligands were the R,R or S,S isomers of 1,2-diaminocyclohexaneor




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