Stimulation of Sulfonamides Antibacterial Drugs Activity as a Result of Complexation with Ru(III): Physicochemical and Biological Study

Antibiotic resistance is a global problem, and one promising solution to overcome this issue is using metallodrugs, which are drugs containing metal ions and ligands. These complexes are superior to free ligands in various characteristics including anticancer properties and mechanism of action. The pharmacological potential of metallodrugs can be modulated by the appropriate selection of ligands and metal ions. A good example of proper coordination is the combination of sulfonamides (sulfamerazine, sulfathiazole) with a ruthenium(III) ion. This work aimed to confirm that the activity of sulfonamides antibacterial drugs is initiated and/or stimulated by their coordination to an Ru(III) ion. The study determined the structure, electrochemical profile, CT-DNA affinity, and antimicrobial as well as anticancer properties of the synthesized complexes. The results proved that Ru(III) complexes exhibited better biological properties than the free ligands.

Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis, DNA/Protein Binding and In Vitro Cytotoxicity Studies

Zn(II) complexes bearing tris[3-(2-pyridyl)-pyrazolyl] borate (Tppy) ligand (1–3) was synthesized and examined by spectroscopic and analytical tools. Mononuclear [TppyZnCl] (1) has a Zn(II) centre with one arm (pyrazolyl-pyridyl) dangling outside the coordination sphere which is a novel finding in TppyZn(II) chemistry. In complex [TppyZn(H2O)][BF4] (2) hydrogen bonding interaction of aqua moiety stabilizes the dangling arm. In addition, solution state behaviour of complex 1 confirms the tridentate binding mode and reactivity studies show the exogenous axial substituents used to form the [TppyZnN3] (3). The complexes (1–3) were tested for their ability to bind with Calf thymus (CT) DNA and Bovine serum albumin (BSA) wherein they revealed to exhibit good binding constant values with both the biomolecules in the order of 104–105 M−1. The intercalative binding mode with CT DNA was confirmed from the UV-Visible absorption, viscosity, and ethidium bromide (EB) DNA displacement studies. Further, the complexes were tested for in vitro cytotoxic ability on four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, HCC1937, and Hs 578T). All three complexes (1–3) exhibited good IC50 values (6.81 to 16.87 μM for 24 h as seen from the MTS assay) results which indicated that these complexes were found to be potential anticancer agents against the TNBC cells.

Chitin conduits modified with DNA-peptide coating promote the peripheral nerve regeneration

Peripheral nerve injury (PNI) is one of the common clinical injuries which needs to be addressed. Previous studies demonstrated the effectiveness of using biodegradable chitin (CT) conduits small gap tubulization technology as a substitute for traditional epineurial neurorrhaphy. Aiming to improve the effectiveness of CT conduits in repairing PNI, we modified their surface with a DNA-peptide coating. The coating consisted of single strand DNA (ssDNA) and its complementary DNA’-peptide mimics. First, we immobilize ssDNA (DNA1+2) on CT conduits by EDC/NHS method to construct CT/DNA conduits. EDC/NHS was used to activate carboxyl groups of modified ssDNA for direct reaction with primary amines on the chitin via amide bond formation. Then, DNA1’-BDNF+DNA2’-VEGF mimic peptide （RGI+KLT）were bonded to CT/DNA conduits by complementary base pairing principle at room temperature to form CT/RGI+KLT conduits. When the surrounding environment rose to a certain point (37℃), the CT/RGI+KLT conduits achieved sustainable release of DNA’-peptide. In vitro, the CT conduits modified with the DNA-peptide coating promoted the proliferation and secretion of Schwann cells by maintaining their repair state. It also promoted the proliferation of HUVECs and axon outgrowth of DRG explants. In vivo, CT/RGI+KLT conduits promoted regeneration of injured nerves and functional recovery of target muscles, which was facilitated by the synergistic contribution of angiogenesis and neurogenesis. Our research brings DNA and DNA-peptide hybrids into the realm of tissue engineering to repair peripheral nerve injury.

Synthesis, Spectroscopic, Antibacterial, Antioxidant, DNA Binding and Cleavage, Molecular Docking Studies of Ni(II) and Cu(II) Complexes of S and N Donor Schiff Base Ligands

Binary metal complexes of the ligands (L), H3FPT and H3FP4MT with Ni(II) and Cu(II) metal ions (M) were synthesized and characterized by different spectral and analytical techniques. Among these complexes, Ni(II)- H3FPT complex was found to be polymeric. The ligands and their complexes inhibited the growth of gram positive and gram negative bacterial strains to a moderate extent. The antioxidant nature of ligands and complexes was also established. Intercalative mode of binding of the complexes with calf thymus (CT) DNA was proposed from electronic absorption titrations, fluorescence quenching studies and viscosity measurements. The complexes showed hydrolytic cleavage of plasmid pBR322. Docking studies of metal complexes with DNA revealed that the complexes of H3FP4MT are more active than H3FPT.

8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis, Anticancer Activities, Solution Chemistry and Interaction with Biomolecules

Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η5-C5Me5)(H2O)3]2+ and [Ru(η6-p-cymene)(H2O)3]2+ ions by pH-potentiometry, UV-visible spectrophotometry and 1H NMR spectroscopy. Due to the zwitterionic structure of the ligands, they possess excellent water solubility as well as their complexes. The complexes exhibit high solution stability in a wide pH range; no significant dissociation occurs at physiological pH. The hybrids and their Rh(η5-C5Me5) complexes displayed enhanced cytotoxicity in human colon adenocarcinoma cell lines and exhibited multidrug resistance selectivity. In addition, the Rh(η5-C5Me5) complexes showed increased selectivity to the chemosensitive cancer cells over the normal cells; meanwhile, the Ru(η6-p-cymene) complexes were inactive, most likely due to arene loss. Interaction of the complexes with human serum albumin (HSA) and calf-thymus DNA (ct-DNA) was investigated by capillary electrophoresis, fluorometry and circular dichroism. The complexes are able to bind strongly to HSA and ct-DNA, but DNA cleavage was not observed. Changing the five-membered proline ring to the six-membered homoproline resulted in increased lipophilicity and cytotoxicity of the Rh(η5-C5Me5) complexes while changing the configuration (L vs. D) rather has an impact on HSA or ct-DNA binding.

Synthesis and Spectroscopic Investigations of Schiff Base Ligand and Its Bimetallic Ag(I) Complex as DNA and BSA Binders

Generation of well-defined potential metallotherapeutics for cancer treatment, one of the most population-threatening diseases, is challenging and an active area of modern research in view of their unique properties and thus multiple possible pathways of action in cells. Specifically, Schiff base ligands were recognized as very promising building blocks for the construction of stable and active complexes of numerous geometries and topologies. Incorporation of Ag(I) ions allows for the formation of flat complexes with potential unoccupied coordination sites, thus giving rise to specific interactions between the metallotherapeutic and biomolecule of interest. Herein, we present the design, synthesis and characterization of new Schiff base ligand L and its Ag(I) bimetallic complex [Ag2L2]2+ with two planar moieties formed around the metal ions and connected through cyclohexane rings, confirmed by X-ray measurements. The compounds were described in context of their potential use as anticancer drugs through DNA and BSA binding pathways by several spectroscopic methods (CD, UV-Vis, fluorescence). We revealed that both, L and [Ag2L2]2+, interact with similar affinity with CT-DNA (Kb~106 M−1), while they differ in the type and strength of interactions with the model albumin–BSA. [Ag2L2]2+ binds BSA in both a dynamic and static manner with the Ksv = 8.8 × 104 M−1 in the Trp-134 and Trp-213 sites, whereas L interacts with BSA only dynamically (KSV = 2.4 × 104 M−1). This found further confirmation in the CD studies which revealed a reduction in α-helix content in the albumin of 16% in presence of [Ag2L2]2+.