P. Kalaivani

Biological evaluation of new nickel(II) metallates: Synthesis, DNA/protein binding and mitochondrial mediated apoptosis in human lung cancer cells (A549) via ROS hypergeneration and depletion of cellular antioxidant pool

A series of novel nickel(II) thiosemicarbazone complexes(1-4) have been prepared and characterized by various spectral, analytical techniques and X-ray crystallography. Further, their efficacy to interact with CT-DNA/BSA has been explored. From the binding studies, it is inferred that complex 4 found to be more active than other complexes. The complexes bound with CT-DNA by intercalation mode. Moreover, static quenching was observed for their interaction with BSA. The new complexes were tested for their in vitro cytotoxicity against human lung adenocarcinoma (A549) cell line. The results showed that the new complexes exhibited significant degree of cytotoxicity at given experimental condition. Further, the results of LDH and NO release supported the cytotoxic nature of the complexes. The observed cytotoxicity of the complexes may be routed through ROS-hypergeneration and lipid-peroxidation with subsequent depletion of cellular antioxidant pool (GSH, SOD, CAT, GPx and GST) resulted in the reduction of mitochondrial-membrane potential, caspase-3 activation and DNA fragmentation. Thus, the data from the present study disclose that the complexes could induce apoptosis in A549 cells through mitochondrial mediated fashion and inhibited the migration of lung cancer cells and by metastasis.

Synthesis, structure, DNA/protein binding and in vitro cytotoxicity of new ruthenium metallates

The reaction of [RuHCl(CO)(PPh3)3] with an equimolar amount of salicylaldehyde-4(N)-methylthiosemicarbazone [H2-(Sal-mtsc)] resulted in two entities, namely [Ru(H-Sal-mtsc)Cl(CO) (PPh3)2] (1) and [Ru(Sal-mtsc)(CO)(PPh3)2] (2) from a single tub. The new complexes were characterized by various spectro (IR, absorption and NMR), analytical and single crystal X-ray diffraction studies. From the crystallographic studies, it is confirmed that in complex 1, the ligand coordinated through the thiolate sulfur and the deprotonated hydrazinic nitrogen N(2), resulting in the formation of an unusual strained four membered chelate ring. The third potential donor, phenolic oxygen, remained uncoordinated. In complex 2, the ligand coordinated as an ONS chelate with the formation of more common five and six membered chelate rings. Complexes 1 and 2 have been tested for their DNA/protein binding properties by taking CT-DNA/lysozyme as models. From the protein binding studies, the alterations in the secondary structure of lysozyme by the ruthenium(II) complexes (1 and 2) were confirmed with synchronous and three-dimensional fluorescence spectroscopic studies. The in vitro cytotoxicity of the newly-synthesized complexes was carried out in two different human tumour cell lines, A549 and HepG2. The cytotoxicity studies showed that complex 2 exhibited higher activity than 1.

Synthesis, DNA/protein binding and in vitro cytotoxic studies of new palladium metallothiosemicarbazones

A series of four new thiosemicarbazone complexes of palladium have been synthesized, characterized and evaluated for their DNA/protein binding with CT-DNA and BSA, respectively. The new complexes bound to CT-DNA by intercalation mode and in protein binding studies, the complexes bound to BSA binding mechanism was found as static quenching. Among them the complex 4 had a strong binding affinity with BSA. In addition, in vitro cytotoxic studies were carried out on lung cancer (A549) and liver cancer (HepG2) cell lines and found that the complexes exhibited better activity than their parent thiosemicarbazone analogues. The complex 3 exhibited better activity than other complexes and this fact supported by the increased accumulation of the complexes in to the cancer cells which are evident from inter cellular uptake studies.

Copper ion mediated selective cleavage of C-S bond in ferrocenylthiosemicarbazone forming mixed geometrical [(PPh3)Cu(μ-S)2Cu(PPh3)2] having Cu2S2 core: toward a new avenue in copper-sulfur chemistry.

Unprecedented selective cleavage of the carbon-sulfur bond of the ferrocenylthiosemicarbazone moiety has been observed for the first time, resulting in the formation of mixed geometrical binuclear copper complex [(PPh(3))Cu(μ-S)(2)Cu(PPh(3))(2)]. Upon trying direct synthesis of the title complex, an unusual tetranuclear [Cu(4)(μ(3)-Cl)(4)(PPh(3))(4)] cubane resulted.

New organometallic ruthenium(II) complexes containing chelidonic acid (4-oxo-4H-pyran-2,6-dicarboxylic acid): synthesis, structure and in vitro biological activity

Two new bivalent organometallic ruthenium complexes [Ru(HL)(CH3CN)(CO)(PPh3)2] (3) and [Ru(HL)(CH3CN)(CO)(AsPh3)2] (4), (HL = 4-oxo-4H-pyran-2,6-dicarboxylic acid) were synthesized, structurally characterized and their biological activities (anti-microbial, DNA–protein interactions, antioxidant and cytotoxic activity studies (MTT, LDH release and NO release)) have been investigated and compared with that of appropriate precursor complexes [RuHCl(CO)(PPh3)3] (1), [RuHCl(CO)(AsPh3)3] (2) and the ligand H2L. The crystal structure of the complex 3 was solved by a single crystal X-ray diffraction technique, which revealed that it is a distorted octahedral with HL as a dibasic bidentate donor and the chelator was observed to undergo C–H activation at one of the ortho positions, leading to the formation of a five membered metallacycle. The in vitro antimicrobial activity was carried out using the well diffusion method against different species of pathogenic bacteria and fungi and complex 4 exhibited a better activity in inhibiting the growth of the tested organisms. DNA–protein interactions of the complexes have been examined by photophysical studies, which revealed that the complexes can bind with DNA through non-intercalation and the complexes strongly quench the intrinsic fluorescence of bovine serum albumin, through a static quenching process. The free radical scavenging ability, assessed by a series of in vitro antioxidant assays involving the DPPH radical, hydroxyl radical, nitric oxide radical, superoxide anion radical, hydrogen peroxide and a metal chelating assay showed that the new complexes 3 and 4 possess excellent radical scavenging properties over 1, 2, H2L, and the standard drugs, vitamin C and BHT. The in vitro cytotoxic activities of the compounds have been validated against A549 cells via an MTT assay, LDH release, NO release and the values were compared with that of the standard drug cisplatin. The results indicated that the new complexes, specifically the complex 3, displayed a higher cytotoxic activity in inhibiting the growth of A549 cells, outperforming by five fold, the standard drug cisplatin.

Synthesis and structural characterization of new ruthenium(II) complexes and investigation of their antiproliferative and metastatic effect against human lung cancer (A549) cells

Reaction of 2-hydroxy-1-naphthaldehyde-4(N)-ethylthiosemicarbazone [H2-(Nap-etsc)] with [RuHCl(CO)(PPh3)3] conferred two entities, namely [Ru(H-Nap-etsc)Cl(CO)(PPh3)2] (1) and [Ru(Nap-etsc)(CO)(PPh3)2]·Cl (2). The new complexes were characterized using various spectroanalytical and X-ray crystallographic techniques. In this reaction the dual coordination behaviour (thiolate/thione) of the ligand was observed. It acted as NS bidentate monobasic and ONS tridentate monobasic in entities 1 and 2 respectively. The binding ability of complexes (1 and 2) to calf thymus DNA (CT DNA)/BSA has been explored by absorption and emission titration methods. The cytotoxic nature of the complexes was evaluated on human lung cancer cells, A549. Complexes induced apoptotic cell death via ROS hypergeneration and mitochondrial membrane damage. In addition these newly synthesized ruthenium complexes inhibited A549 cell migration, as evidenced by wound healing assay. The activity of the complexes was found to be very high by comparing with cisplatin, a conventional standard. The time dependent release of the complexes from porous system was investigated by taking mesoporous silica as the host material. It was shown that the main portion of the embedded complexes was released after 20 h and reached a maximum after 96 h.

Photophysical properties and in vitro cytotoxicity studies of new Ru(II) carbonyl complexes and mixed geometrical Ru(II)–Ni(II) complex in HS-DNA/BSA protein and human lung (A549) and liver (HepG2) cells

Two new ruthenium(II) carbonyl complexes have been synthesized from [RuHCl(CO)(PPh3)3] and 2-hydroxy-1-naphthaldehydethiosemicarbazone [H2-(Nap-tsc)]. The stoichiometric reaction afforded two different complexes (1 and 2) exhibiting different structural motifs. In complex 1, the ligand coordinated through the N(2) nitrogen and thiolate sulphur by forming a strained four member chelate ring by leaving three donor sites (phenolic oxygen, N1 nitrogen and terminal nitrogen) uncoordinated. However, in complex 2, it coordinated as an ONS tridentate with the formation of a six member and a five member ring. In order to utilize the three unutilized donor sites in complex 1, it was reacted further with [NiCl2(PPh3)2], which resulted in the formation of a new hetero bimetallic complex 3 wherein all the donor atoms of the ligand were utilized. The complexes have been characterized analytically and spectroscopically and X-ray diffraction (1, 3) and have also been evaluated for their binding affinity with HS-DNA. The electrostatic binding of the complexes with DNA was evident from absorption and fluorescence titration experiments. The binding interaction between the complexes 1–3 and bovine serum albumin (BSA) was studied by absorption, fluorescence and synchronous spectra at room temperature. From the results, it is inferred that complex 2 had a better binding ability with the tryptophan residues of BSA. The mechanism of complex interaction was found as static quenching. The in vitro cytotoxicity of metal complexes (1–3) has been evaluated by colorimetric assay (MTT assay).