We report [RuII(L)(η6-p-cym)Cl] (1 and 2) and
[PtII(L)(DMSO)Cl] (3 and 4) complexes,
where L is a chelate imine ligand derived from chloroethylamine and
salicylaldehyde (HL1) or o-vanillin (HL2). The complexes were characterized by single-crystal X-ray diffraction
and other analytical techniques. The 1H nuclear magnetic
resonance data show that both the Ru(II) and Pt(II) complexes start
forming the aquated complex within an hour. The aquated complexes
are stable at least up to 24 h. The complexes bind to the N7 of the model nucleobase 9-ethylguanine (9-EtG). Interaction with
calf thymus (CT) DNA shows moderate binding interactions with binding
constants, K
b (3.7 ± 1.2) ×
103 M–1 and (4.3 ± 1.9) × 103 M–1 for 1 and 3, respectively. The complexes exhibit significant antiproliferative
activity against human pancreas ductal adenocarcinoma (Mia PaCa-2),
triple negative metastatic breast adenocarcinoma (MDA-MB-231), hepatocellular
carcinoma (Hep G2), and colorectal adenocarcinoma (HT-29) cell lines.
The studies show that with the same ligand the Pt(II) complexes are
more potent than the Ru(II) complexes. The in vitro potencies of all the complexes toward pancreatic cancer cell line
MIA PaCa-2 are more than cisplatin (CDDP). The Pt(II) and Ru(II) complexes
show similar binding constants with CT-DNA, but the reactivity of
the Pt(II) complex 3 with 9-EtG is faster and their overall
cell killing pathways are different. This is evident from the arrest
of the cell cycle by the Ru(II) complex 1 in the G2/M
phase in contrast to the SubG1 phase arrest by the Pt(II) complex 3. The immunoblot study shows that 3 increases
cyclin D and Bcl-2 expression in MDA-MB-231 due to the SubG1 phase
arrest where these proteins express in greater quantities. However,
both 1 and 3 kill in the apoptotic pathway
via dose-dependent activation of caspase 3. Complex 3 depolarizes the mitochondria more efficiently than 1, suggesting its higher preference for the intrinsic pathway of apoptosis.
Our work reveals that the same bidentate ligand with a change of the
metal center, viz, Pt(II) or Ru(II), imparts significant
variation in cytotoxic dosage and pathway of action due to specific
intrinsic properties of a metal center (viz, coordination
geometry, solution stability) manifested in a complex.