Probing the interaction of new and biologically active Pd(II) complex with DNA/BSA via joint experimental and computational studies along with thermodynamic, NLO, FMO and NBO analysis

Treatment with transition metal complexes is an efficient method to fight with cancer. Therefore, a new transition metal complex formulated as [Pd(1, 3-pn)(acac)]Cl (pn and acac stand for propylendiamine and acetylacetonate, respectively) was synthesized and analyzed using 1H NMR, Fourier transform infrared, electronic absorption spectroscopy techniques as well as elemental analysis and conductivity measurement. The geometry optimization, frontier molecular orbital (FMO) analysis, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis and nonlinear optical (NLO) property were accomplished by density functional theory (DFT) at B3LYP level with 6-311G(d,p)/aug-cc-pVTZ-PP basis set. Preliminary determination of antitumor activity and lipophilicity of this metal complex was performed experimentally and the promising results were obtained.
This encouraged us to study the interaction and binding mode/modes of this complex with DNA as the primary receptor for the chemotropic drugs and BSA as the transporter protein in the circulatory system. For this reason, the binding of newly made complex was assessed in-vitro under physiological state using experimental and in-silico molecular modeling studies. So, the CT-DNA binding study of this complex was explored using spectrofluorometric as well as spectrophotometric techniques, viscosity and gel electrophoresis experiments. Furthermore, fluorescence, UV-Vis, F[Formula: see text]rster resonance energy transfer and circular dichroism studies were carried out for BSA binding. The experimental and computational interaction studies showed that [Pd(1, 3-pn)(acac)]Cl complex binds to the minor groove of CT-DNA and interacts with BSA by van der Waals forces and hydrogen bond.

In vitro biological activity of copper(II) complexes with NSAIDs and nicotinamide: Characterization, DNA- and BSA-interaction study and anticancer activity

Through the reaction of copper(II) acetate with nicotinamide (pyridine-3-carboxylic acid amide, niacinamide) and some derivatives of N-phenylanthranilic acid (fenamates), seven new mixed-ligand copper(II) compounds were isolated: [Cu(tolf-O)(tolf-O,O’)nia-N)2(EtOH)] (1), [Cu(tolf-O)(tolf-O,O’)(nia-N)2(MeOH)] (2), [Cu(meclf-O)(meclf-O,O’)(nia-N)2(EtOH)] (3), [Cu(meclf-O)(meclf-O,O’)(nia-N)2(MeOH)] (4), [Cu(meclf-O)(meclf-O,O’)(nia-N)2(ACN)] (5), [Cu(mef-O)(mef-O,O’)(nia-N)2(EtOH)] (6) and [Cu(mef-O)(mef-O,O’)(nia-N)2(ACN)] (7) containing a molecule of relevant solvent as ligand in their primary crystal structure (tolf = tolfenamate, meclf = meclofenamate, mef = mefenamate, nia = nicotinamide, EtOH = ethanol, MeOH = methanol, ACN = acetonitrile). The structures of the complexes were determined by single-crystal X-ray analysis.
The intermolecular interactions were studied by Hirshfeld surface analysis. The complexes were characterized by IR, UV-vis and EPR spectroscopy and their redox properties were determined by cyclic voltammetry. The interaction of the complexes with bovine serum albumin was studied by fluorescence emission spectroscopy and the albumin-binding constants of the compounds were calculated.
The interaction of the complexes with calf-thymus DNA was monitored by diverse techniques (UV-vis spectroscopy, cyclic voltammetry, viscosity measurements) suggesting intercalation as the most possible mode of binding. DNA-competitive studies of the complexes with ethidium bromide were monitored by fluorescence emission spectroscopy. The cytotoxic effects of copper(II) complexes on lung carcinoma cells and healthy cells were determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] colorimetric technique.


Burkholderia pseudomallei pathogenesis in human skin fibroblasts: A Bsa type III secretion system is involved in the invasion, multinucleated giant cell formation, and cellular damage

Burkholderia pseudomallei-a causative agent of melioidosis that is endemic in Southeast Asia and Northern Australia-is a Gram-negative bacterium transmitted to humans via inhalation, inoculation through skin abrasions, and ingestion. Melioidosis causes a range of clinical presentations including skin infection, pneumonia, and septicemia. Despite skin infection being one of the clinical symptoms of melioidosis, the pathogenesis of B. pseudomallei in skin fibroblasts has not yet been elucidated.

In this study, we investigated B. pseudomallei pathogenesis in the HFF-1 human skin fibroblasts. On the basis of co-culture assays between different B. pseudomallei clinical strains and the HFF-1 human skin fibroblasts, we found that all B. pseudomallei strains have the ability to mediate invasion, intracellular replication, and multinucleated giant cell (MNGC) formation. Furthermore, all strains showed a significant increase in cytotoxicity in human fibroblasts, which coincides with the augmented expression of matrix metalloproteinase-2.

Using B. pseudomallei mutants, we showed that the B. pseudomallei Bsa type III secretion system (T3SS) contributes to skin fibroblast pathogenesis, but O-polysaccharide, capsular polysaccharide, and short-chain dehydrogenase metabolism do not play a role in this process. Taken together, our findings reveal a probable connection for the Bsa T3SS in B. pseudomallei infection of skin fibroblasts, and this may be linked to the pathogenesis of cutaneous melioidosis.