New organometallic drug candidates
[Ph2Sn(HL)], 1, and [Ru(η6--p-cymene)(HL)Cl], 2, were designed
and synthesized by in situ reaction of a
Schiff base ligand (HL) and diphenyltin dichloride and [RuCl2(p-cymene)]2, respectively. The drug
candidates 1 and 2 have been characterized
by spectroscopic methods (Fourier-transform infrared spectroscopy,
UV–vis, and 1H/13C NMR), elemental analysis,
and single X-ray crystallographic studies (in case of 1). The ground-state geometry optimization of 1 and 2 was performed by density functional theory calculations.
The interaction of 1 and 2 with tRNA was
assessed by absorption spectroscopy, cyclic voltammetry, circular
dichroism, and ethidium bromide displacement assay using fluorescence
emission spectroscopy to determine their potential to act as antitumor
agents. The cytotoxicity of 1 and 2 was
screened against human liver carcinoma (Huh7), prostate cancer (Du145),
and the normal prostate cell line (PNT 2). The results implicated
a dose-dependent growth inhibition of the two cancer cells at concentrations
(2.5–15 μM) of 1 and 2 with
the treatment after 48 h. Interestingly, 1 revealed good
selective activity toward the liver cancer cell line (Huh7). Furthermore,
both the drug candidates 1 and 2 were found
to be nontoxic toward the PNT 2 normal cell line. These studies lay
a paradigm for rational efficacious drug design for chemotherapeutic
intervention in cancers using new tailored organometallic drug entities;
organotin(IV) and organoruthenium(II) have been demonstrated to be
viable for the safe administration and specific targeted drug uptake
by the resistant cancerous cell lines at low intracellular concentrations.
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