Spectroscopic and molecular modeling methods to investigate the interaction between psycho-stimulant modafinil and calf thymus DNA using ethidium bromide as a fluorescence probe.

Interaction type of modafinil with calf thymus DNA (ct-DNA) was examined systematically using ethidium bromide (EB) as a fluorescence probe by fluorescence spectroscopy, UV-Vis spectroscopy, viscosity and molecular docking method. The fluorescence quenching mechanism of ct-DNA-EB by modafinil can be combination of static and dynamic quenching. Results of UV-Vis absorption, competitive binding with Hoechst 33258, ionic strength effect studies, viscosity measurements were confirmed that the interaction type of modafinil with ct-DNA was intercalation. According to docking studies R-modafinil showed better interaction with ct-DNA which is consistent with known pharmacological properties of modafinil. The calculated thermodynamic parameters, enthalpy and entropy change, suggested that the driven forces are hydrogen bonding or van der Walls forces. Results of the docking studies were compatible with the experimental results and confirmed the hydrogen bond formation between modafinil and ct-DNA.

Multispectroscopic and Computational Investigation of ct-DNA Binding Properties with Hydroxybenzylidene Containing Tetrahydrocarbazole Derivative.

Mode of interaction of a new tetrahydrocarbazole derivative with ct-DNA has been investigated systematically using fluorescence spectroscopy, UV-Vis spectroscopy and circular dichroism spectroscopy. It is concluded that TAH could intercalate into the base pairs of ct-DNA, and the fluorescence quenching by ct-DNA was static quenching type. Beside the multispectroscopic results, computational studies were done. Molecular docking results revealed that the TAH-DNAs complexes might be classified as druggable molecule in drug design. Additionally, DNA binding studies exhibited that TAH complexes have different interaction and orientation abilities to each DNA isomer. Combination of experimental and computational data showed that reported TAH is promising structure and deserves further applications.

Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti-inflammatory properties: Synthesis, biological evaluation and molecular modeling studies.

3-Substituted-1,2,4-triazole-5-thiones are versatile synthetic intermediates for the preparation of several biologically active N-bridged heterocyclic compounds, given that they have two reactive sites, thiocarbonyl and an amine nitrogen (N1/N4). For several years, our interest has focused on the synthesis of novel heterocyclic systems derived from 3-substituted-1,2,4-triazole-5-thiones having analgesic/anti-inflammatory activity. In this study, a series of novel thiazolo[3,2-b]-1,2,4-triazole-6(5H)-one derivatives bearing naproxen was synthesized and evaluated for their in vivo analgesic and anti-inflammatory properties in acute experimental pain and inflammation models. The compounds were also tested for their ulcerogenic potential. Our findings showed that all the newly synthesized derivatives attenuate nociception and inflammation compared with a control. All the synthesized compounds exhibited much lower ulcerogenic risk than the standard drugs indomethacin and naproxen. Some compounds with significant analgesic and/or anti-inflammatory activities as well as low ulcer scores were further evaluated for in vitro COX-1 and COX-2 inhibitory potential in a COX-catalyzed prostaglandin biosynthesis assay. Among the tested compounds, compound 1q showed the highest selectivity index (SI) of 4.87. The binding mode for some of the tested compounds to the cyclooxygenase (COX) enzymes was predicted using docking studies.

McbR/YncC: implications for the mechanism of ligand and DNA binding by a bacterial GntR transcriptional regulator involved in biofilm formation.

MqsR-controlled colanic acid and biofilm regulator (McbR, also known as YncC) is the protein product of a highly induced gene in early Escherichia coli biofilm development and has been regarded as an attractive target for blocking biofilm formation. This protein acts as a repressor for genes involved in exopolysaccharide production and an activator for genes involved in stress response. To better understand the role of McbR in governing the switch from exponential growth to the biofilm state, we determined the crystal structure of McbR to 2.1 Å. The structure reveals McbR to be a member of the FadR C-terminal domain (FCD) family of the GntR superfamily of transcriptional regulators (this family was named after the first identified member, GntR, a transcriptional repressor of the gluconate operon of Bacillus subtilis). Previous to this study, only six of the predicted 2800 members of this family had been structurally characterized. Here, we identify the residues that constitute the McbR effector and DNA binding sites. In addition, comparison of McbR with other members of the FCD domain family shows that this family of proteins adopts highly distinct oligomerization interfaces, which has implications for DNA binding and regulation.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance.

In an effort to establish new candidates with improved analgesic and anti-inflammatory activities and lower ulcerogenic risk, a series of thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one derivatives of ibuprofen were synthesized. All compounds were evaluated for their in vivo anti-inflammatory and analgesic activities in mice. Furthermore, the ulcerogenic risks of the compounds were determined. In general, none of the compounds represent a risk for developing stomach injury as much as observed in the reference drugs ibuprofen and indomethacin. The compounds carrying a 3-phenyl-2-propenylidene (1a), (biphenyl-4-yl)methylidene (1f) and (1-methylpyrrol-2-yl)methylidene (1n) at the 6th position of the fused ring have been evaluated as potential analgesic/anti-inflammatory agents without a gastrointestinal side effect. These new compounds, therefore, deserve further attention to develop new lead drugs.