DNA/Protein Binding, Molecular Docking, and in Vitro Anticancer Activity of Some Thioether-Dipyrrinato Complexes

Syntheses and characterizations of
the arene ruthenium [(η6-C6H6)­RuCl­(4-mtdpm)] (1), [(η6-p-MeC6H4Pri)­RuCl­(4-mtdpm)] (2), and structurally
analogous rhodium/iridium complexes [(η5-C5Me5)­RhCl­(4-mtdpm)] (3) and [(η5-C5Me5)­IrCl­(4-mtdpm)] (4) [4-mtdpm = 5-(4-methylthiophenyl)­dipyrromethene] have been reported.
Their identities have been established by satisfactory elemental analyses,
electrospray ionization-mass spectrometry (ESI-MS), FT-IR, NMR (1H, 13C), UV/vis, emission spectral, and electrochemical
studies. Structure of the representative complex 3 has
been authenticated by X-ray single crystal analyses. The complexes 1–4 effectively bind with calf thymus
DNA (CT DNA) through intercalative/electrostatic interactions. In
addition, these exhibit significant cytotoxicity toward Dalton lymphoma
(DL) cell line and cause static quenching of the bovine serum albumin
(BSA) fluorophore. The antiproliferative activity, morphological changes,
and apoptosis have been evaluated by MTT assay, acridine orange/ethidium
bromide (AO/EtBr) fluorescence staining, and DNA ladder assay. Mode
of interaction of the complexes with DNA/protein has also been supported
by molecular docking. Various studies revealed remarkable decrease
in the in vitro DL cell proliferation and induction of the apoptosis
by 1–4, which lies in the order 2 > 1 > 4 > 3.