Interaction of acridinedione dye with a globular protein in the presence of site selective and site specific binding drugs: Photophysical techniques assisted by molecular docking methods.

Photophysical investigations and molecular docking studies of photoinduced electron transfer (PET) based fluorophores of acridine family with a globular protein, Bovine Serum Albumin (BSA) bound to non-narcotic drugs like phenylbutazone (PB) and flufenamic acid (FA) were carried out in aqueous solution. PB and FA are site specific and site selective drugs, wherein PB predominantly binds at the site (I) whereas FA selectively orients towards site (II) of BSA. Acridinedione (AD) dyes, both resorcinol and dimedone based are hydrophobic in nature and exhibits a combination of both hydrophobic and hydrogen-bonding interactions that are based on the binding sites in BSA. The extent of displacement of AD from the binding sites of BSA by PB and FA are elucidated and established from variation in the fluorescence lifetime and relative amplitude distribution of free and dye bound in site (I) and site (II). The extent of binding affinity of PB-BSA and FA-BSA in the presence of AD is minimal when compared to other site I and II drugs. This is attributed to AD dye bound to several amino acid residues present in BSA such that the dye prefers multiple binding sites in BSA even in the presence of FA and PB. Further, the dye bound to several amino acid residues of BSA ascertains the combination of hydrogen-bonding, hydrophobic interactions, pi-pi and pi-alkyl interaction apart from the binding through sites (I) and (II) from molecular docking methods. The combination of fluorescence tools with molecular modelling techniques provides an excellent approach in determining the stability of these complexes containing competitive guest molecules in the presence of a fluorescence probe and the binding characteristics of dye in a micro heterogeneous environment.

Seven membered chelate Pt(ii) complexes with 2,3-di(2-pyridyl)quinoxaline ligands: studies of substitution kinetics by sulfur donor nucleophiles, interactions with CT-DNA, BSA and in vitro cytotoxicity activities.

Dichloro platinum(ii) complexes coordinated with 2,3-di(2-pyridyl)quinoxaline ligands which form seven-membered chelates namely, bpqPtCl2, dmbpqPtCl2 and bbqPtCl2 (where bpq, dmbpq and bbq are 2,3-di(2-pyridyl)quinoxaline, 6,7-dimethyl-2,3-di(2-pyridyl)quinoxaline and 2,3-bis(2'pyriyl)benzo[g]quinoxaline, respectively) were synthesized, characterised and their respective hydrated product complexes namely, bpqPt(OH2)2 2+, dmbpqPt(OH2)2 2+ and bbqPt(OH2)2 2+ were prepared by chloride metathesis. The substitution kinetics of the aquated cations by thiourea nucleophiles indicated that the two aqua ligands are substituted simultaneously according to the rate law: k obs = k 2[Nu]. This is followed by a forced dechelation of the ligands from the Pt (II) to form Pt(Nu)4 2+ species. The dechelation step is considerably slow to be monitored reliably. The rate of substitution is marginally enhanced by introducing two methyl groups and by extending the π-conjugation on the bpq core ligand. The reactivity order increased as bpqPt(OH2)2 2+ < dmbpqPt(OH2)2 2+ < bbqPt(OH2)2 2+. Reactivity trends were well supported by theoretical computed DFT electronic descriptors. The interactions of the Pt(ii) complexes with CT-DNA and BSA were also examined spectroscopically in tris buffers at pH 7.2. Spectroscopic and viscosity measurements suggested strong associative interactions between the Pt(ii) complexes and CT-DNA, most likely through groove binding. In silico theoretical binding studies showed energetically stable poses through associative non-covalent interactions. In vitro MTT cytotoxicity IC50 values of the Pt(ii) complexes on human liver carcinoma cells (HepG2) cancer cell lines revealed bbqPtCl2 as the least active. The fluorescence staining assays revealed the morphological changes suggested early apoptotic induction as well as non-specific necrosis.

Phytosynthesized gold nanoparticles from C. roxburghii DC. leaf and their toxic effects on normal and cancer cell lines.

Gold nanoparticles are considered of great importance compared to other noble metal nanoparticles and its wide range of applications like pharmaceutics, therapeutics and diagnostics etc. During the past decade, phytosynthesized gold nanoparticles (AuNPs) are more focused in in vitro and in vivo study. The present study was focused on the gold chloride and phytosynthesized gold nanoparticles from aqueous leaf extract of Cassia roxburghii and their toxic effects on African green monkey normal kidney Vero cell line and three different cancer cell lines such as HepG2, MCF7 and HeLa. Phytosynthesized AuNPs were characterized by HRTEM, EDX, XRD and FTIR analysis. The particles size range of 25-35nm was confirmed by HRTEM. The elemental gold and the crystalline nature of AuNPs were confirmed by EDX and XRD, respectively. The reduction of functional groups was confirmed by FTIR. In in vitro study, the IC50 of HepG2 cells was found to be 30µg/ml compared to other cell lines, HeLa and MCF7 cell line showing IC50 of 50µg/ml and normal Vero cell line also nontoxic up to 75µg/ml confirmed by MTT assay. Further, apoptosis in HepG2 was analyzed by fluorescence microscope and DNA fragmentation was observed in HepG2 treated cells. These results suggested that phytosynthesized AuNPs of C. roxburghii extract clearly limited toxic on normal cells but toxic in cancer cells.

Structural characterization, antioxidant and in vitro cytotoxic properties of seagrass, Cymodocea serrulata (R.Br.) Asch. & Magnus mediated silver nanoparticles.

The present study pertains to the synthesis, structural elucidation, antioxidant and in vitro cytotoxic properties of silver nanoparticles (AgNPs) from marine angiosperm, Cymodocea serrulata aqueous extract (CSAE). The characterization was made through UV-Visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), zeta potential and dynamic light scanning (DLS) analyses. The UV-Vis spectrum resulted in a strong surface plasmon resonance (SPR) at 430 nm. The average crystalline size of the AgNPs was predicted through XRD peaks that indicated the 2 theta values of 37.84°, 44.06°, 64.42° and 77.74° for Bragg's refraction index. The functional groups responsible for the bio-reduction of Ag(+) into Ag(0) were focused through FTIR spectrum. The FESEM images showed that the C. serrulata mediated AgNPs (CS-AgNPs) were spherical in shape. DPPH assay revealed the higher free radical scavenging activity in CS-AgNPs, when compared to CSAE. The cytotoxicity assay on the cervical cancer (HeLa) and African green monkey kidney (Vero) cells upon treatment with CSAE: 107.7 & 124.3 µgml(-1) and CS-AgNPs: 34.5 & 61.24 µgml(-1), respectively showed good inhibition rate. These findings highlight the fact that C. serrulata could be a potential source for developing potent drugs and further studies are needed.