Rais Ahmad Khan

Chiral heterobimetallic complexes targeting human DNA-topoisomerase Iα

The chiral monometallic Cu(II) (1) and Zn(II) (2) and heterobimetallic Cu(II)-Sn(IV) and Zn(II)-Sn(IV) complexes with tridentate chiral Schiff base -ONO-ligand in the presence of nitrogen donor heterocyclic ligand imidazole; were prepared and characterized by various physico-chemical and spectroscopic methods. Preliminary complex-DNA interaction studies employing optical methods revealed that 3 displayed a higher propensity towards the drug target DNA double helix and recommended predominantly an electrostatic mode of interaction as well as a groove binding affinity of the complex with CT-DNA. This was quantified by Kb and KSV values of complexes 1-4, which demonstrated a multifold increase in complex 3 binding to CT DNA and clearly demonstrates its potency to act as a chemotherapeutic agent. Furthermore, the gel electrophoretic patterns of supercoiled pBR322 DNA with varying concentrations of complex 3 exhibits the ability to cleave DNA and follow a freely diffusible radical mechanism. The antiproliferative effects of complex 3 on human hepatoma cancer cells (Huh7) was investigated. Human Topo I inhibition assay by complex 3 was performed and results confirmed significantly good activity at lower concentrations than some of the classical Topo I inhibitors. Additionally, complex 3 was investigated for the expression of MMP-2 and TGF-β by real time PCR. The cellular uptake of complex 3 by HeLa cells was studied by confocal microscopy.

Biogenic synthesis of Zinc oxide nanostructures from Nigella sativa seed: Prospective role as food packaging material inhibiting broad-spectrum quorum sensing and biofilm

Bacterial spoilage of food products is regulated by density dependent communication system called quorum sensing (QS). QS control biofilm formation in numerous food pathogens and Biofilms formed on food surfaces act as carriers of bacterial contamination leading to spoilage of food and health hazards. Agents inhibiting or interfering with bacterial QS and biofilm are gaining importance as a novel class of next-generation food preservatives/packaging material. In the present study, Zinc nanostructures were synthesised using Nigella sativa seed extract (NS-ZnNPs). Synthesized nanostructures were characterized hexagonal wurtzite structure of size ~24 nm by UV-visible, XRD, FTIR and TEM. NS-ZnNPs demonstrated broad-spectrum QS inhibition in C. violaceum and P. aeruginosa biosensor strains. Synthesized nanostructures inhibited QS regulated functions of C. violaceum CVO26 (violacein) and elastase, protease, pyocyanin and alginate production in PAO1 significantly. NS-ZnNPs at sub-inhibitory concentrations inhibited the biofilm formation of four-food pathogens viz. C. violaceum 12472, PAO1, L. monocytogenes, E. coli. Moreover, NS-ZnNPs was found effective in inhibiting pre-formed mature biofilms of the four pathogens. Therefore, the broad-spectrum inhibition of QS and biofilm by biogenic Zinc oxide nanoparticles and it is envisaged that these nontoxic bioactive nanostructures can be used as food packaging material and/or as food preservative.

Light-stable bis(norharmane)silver(I) compounds: Synthesis, characterization and antiproliferative effects in cancer cells

Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) and having the general formula [Ag(Hnor)2](anion) (anion=ClO4(-), NO3(-) and BF4(-)) [Ag(Hnor)2(MeCN)](PF6) are reported, and studied in detail regarding their coordination mode and in vitro antiproliferative effects. X-ray structural analysis revealed that the complex with the PF6(-) anion has a MeCN solvent molecule weakly coordinated to Ag(I), making the metal coordination T-shaped, while the other compounds present the classical linear Ag(I) coordination. The compounds showed certain cell growth inhibitory effects in two different cancer cell lines, with the perchlorate containing complex being the most toxic and in fact comparable to cisplatin. Notably, the compounds are stable in visible light; and the luminescence in the solid state was found to be extremely weak, whereas in MeOH solution all compounds show a moderate to weak emission band at 375 nm, when excited at 290 nm.

Insights into the strong in-vitro anticancer effects for bis(triphenylphosphane)iminium compounds having perchlorate, tetrafluoridoborate and bis(chlorido)argentate anions

Three new compounds containing the bis(triphenylphosphane)iminium cation (PPN(+)) with ClO4(-), BF4(-) and [AgCl2](-) as counter anions have been synthesized and structurally characterized. The two derivatives with ClO4(-) and BF4(-) were found to be isostructural by single crystal X-ray diffraction. Interestingly, the three compounds show extremely potent antiproliferative effects against the human cancer cell line SKOV3. To gain insights into the possible mechanisms of biological action, several intracellular targets have been considered. Thus, DNA binding has been evaluated, as well as the effects of the compounds on the mitochondrial function. Furthermore, the compounds have been tested as possible inhibitors of the seleno-enzyme thioredoxin reductase.

Heteroleptic Copper(I) Complexes of “Scorpionate” Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode

New copper(I) complexes [CuCl(PPh3)(L)] (1: L = LA = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane; (2: L = LB = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV–Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials.

Coumarin centered copper(II) complex with appended-imidazole as cancer chemotherapeutic agents against lung cancer: molecular insight via DFT-based vibrational analysis

Coumarins are well known for the design of target-specific therapeutics for cancer oncology. In lieu of their potential applications as antitumor chemotherapeutics, a new coumarin-based copper(II) complex 1 was synthesized employing 6-methyl-3-((quinolin-8-ylimino)methyl)-3H-chromene-2,4-dione (L). The structure elucidation of 1 was done by various spectroscopic techniques (viz., IR, Raman, UV-vis, and EPR), elemental analysis and single crystal X-ray diffraction. Raman and IR combined with B3LYP/DFT frequency calculations were used to characterize the lattice dynamics with an emphasis on the doming mode vibrations of the copper site. Prominent features in the Raman and far-IR spectrum, indicative of doming modes, appeared in the 35–150 cm−1, other out-of-plane and in-plane mode of vibrations in the range of 160–250 cm−1 and 260–700 cm−1, respectively. Furthermore, preliminary in vitro binding studies of L and complex 1 with CT-DNA were carried out by various biophysical techniques. The results demonstrated that 1 avidly binds to CT DNA as compared to L and cisplatin (marketed drug in use for treating solid cancers) via a partial intercalative mode. Furthermore, pBR322 cleavage studies of 1 revealed the hydrolytically double-stranded cleavage pattern verified by T4 ligase religation. The cytotoxicity activity of L and complex 1 was carried out to evaluate cell growth inhibition in a human alveolar epithelial A549 cancer cells (human lung carcinoma) by the MTT assay. Interestingly, the IC50 value of complex 1 was found to be 4.6 ± 0.3 μM which is significantly lower as compared to the IC50 values of previously reported Cu(II) complexes. Furthermore, in the presence of 1, the level of reactive oxygen species (ROS) and thiobarbituric acid reactive substance (TBARS) displayed significant increase, coupled with reduced glutathione (GSH) levels on the A549 cancer cell. Thus, the results confirm the important role of ROS generation and discover Cu(II) complex 1 induced cell apoptosis and validate its potential to act as a robust anticancer drug entity.

Biological evaluation of dinuclear copper complex/dichloroacetic acid cocrystal against human breast cancer: design, synthesis, characterization, DFT studies and cytotoxicity assays

Binuclear copper(II) cocrystal “[Cu2(valdien)2⋯2Cl2CHCOOH],” 1 was synthesized from H2valdien scaffold and anticancer drug pharmacophore “dichloroacetic acid” embedded with two Cu(II) connected via a hydrogen bonded network. [Cu2(valdien)2⋯2Cl2CHCOOH] 1 was thoroughly characterized by single-crystal XRD and by other spectroscopic techniques. The non-covalent interaction (NCI) index and Hirshfeld surface analysis were used to study the various kinds of interactions (O⋯H, N⋯H, H⋯Cl, Cu⋯H, C⋯O, N⋯O, C⋯Cl, and O⋯Cl, etc.) responsible for the stabilization of crystal lattice. [Cu2(valdien)2⋯2Cl2CHCOOH] 1 was validated as potential antitumor drug entity by studying its DNA binding profile, cleavage mechanism with pBR322 by gel electrophoretic assay and in vitro cytotoxicity on MCF-7 cancer cell lines. The mechanistic pathways were also deduced via dual staining AO/EB of cancer cells which confirmed the potential of the cocrystal [Cu2(valdien)2⋯2Cl2CHCOOH] 1 to act as effective anticancer agent towards breast cancers.

Synthesis, characterization of α-amino acid Schiff base derived Ru/Pt complexes: Induces cytotoxicity in HepG2 cell via protein binding and ROS generation

We have synthesized two new complexes of platinum (1) and ruthenium (2) with α-amino acid, l-alanine, and 2,3-dihydroxybenzaldehyde derived Schiff base (L). The ligand and both complexes were characterized by using elemental analysis and several other spectroscopic techniques viz; IR, (1)H, (13)C NMR, EPR, and ESI-MS. Furthermore, the protein-binding ability of synthesized complexes was monitored by UV-visible, fluorescence and circular dichroism techniques with a model protein, human serum albumin (HSA). Both the PtL2 and RuL2 complexes displayed significant binding towards HSA. Also, in vitro cytotoxicity assay for both complexes was carried out on human hepatocellular carcinoma cancer (HepG2) cell line. The results showed concentration-dependent inhibition of cell viability. Moreover, the generation of reactive oxygen species was also evaluated, and results exhibited substantial role in cytotoxicity.

In vivo assessment of newly synthesized achiral copper(II) and zinc(II) complexes of a benzimidazole derived scaffold as a potential analgesic, antipyretic and anti-inflammatory

Two new complexes of copper(II), [CuL2], and zinc(II), [ZnL2], with a tridentate –ONN′– Schiff base ligand (L), a bioactive scaffold derived from 2-aminobenzimidazole and 2-hydroxy-3-methoxybenzaldehyde, were synthesized and characterized using various spectroscopic techniques, viz, IR, 1H and 13C NMR, EPR, HRMS, and elemental analysis and purity analysis using UPLC studies. Both the complexes are non-electrolytic by nature. The newly synthesized compounds were screened for acetic acid-induced analgesic and yeast-induced antipyretic activities in mice and carrageenan-induced paw edema in rats (anti-inflammatory). The results showed that the [CuL2] compound (at 100 mg kg−1 b.w) possessed potent anti-inflammatory activity whereas [ZnL2] (at 50 mg kg−1 and 100 mg kg−1 b.w) exhibited significant analgesic activity when compared with standard drugs. Both the complexes have apparently moderate and nearly akin antipyretic activity.

Polarographic Study of trans-Dioxotetracyanotungstate(IV) Ion

The Polarographie behaviour of tetrapotassium dioxotetracyanotungstate (IV), Ki [W1V 0% (CN)i] · 6H2O at dropping mercury electrode (dme) has been investigated in aqueous medium in the presence of 0.1 M KNO3 and 0.01 °/o gelatin. The complex was found to be oxidized step-by-step to the tungstate (VI) state. The resulting tungstate (VI) complex is presumed to be hexa-coordinated trans[WVIO2 ( ) ]*~ like the original tungstate (IV) complex, and the electrode process can be given as: lW^02(CN)t]*-j—> [Wv02(CN)4]3-