Lanthanides (Lns) have recently been recognized as essential cofactors for certain bacterial enzymes, such as methanol dehydrogenase (MDH), yet their poor bioavailability under physiological conditions has long suggested the existence of Ln-binding metallophores termed lanthanophores. In this context methylolanthanin (MLL), a chelator which is potentially involved in Ln-uptake of methylotrophic bacteria, was recently isolated and characterized. Herein we synthesized two novel MLL derivatives, ortho- and meta-MLL, for comparative studies in order to gain a deeper insight into the unusual 4-hydroxy benzoate moiety of native para-MLL. For this we implemented UV-vis titrations, time-resolved laser-induced fluorescence spectroscopy (TRLFS) and ion mobility spectrometry-mass spectrometry (IMS-MS) complemented by density functional theory (DFT) calculations to investigate metal-binding behavior in both solution and gas phases to trivalent Lns. As our binding studies revealed that both artificial chelators tend to precipitate Lns similar to the native para-MLL under biologically relevant conditions (pH: 6.0), rather than solubilizing them, the solubility products of their Eu3+ complexes were determined. Due to the structural resemblance of the MLL derivatives to the siderophore rhodopetrobactin B (RPB B), we also investigated iron binding. In this regard ortho-MLL stood out in our analysis and showed a distinctly different binding behavior from the other two derivatives.
In this study, a coumarin based organic chemosensor bearing dicyanovinylene group has been used for the detection of CN- anion found in many living areas as environment and nature pollutant. 7-hydroxycoumarin also known as umbelliferone has been derivatized at the 3-position with dicyanovinylene group. Molecular designation of the molecule fits the donor-π-acceptor (D-π-A) systems. Here, hydroxy group at 7-position of umbelliferone is responsible for electron donation and dicyanovinylene group at 3-position is responsible for electron withdrawal. Structural characterization of the molecule has been accomplished by NMR and HRMS spectroscopic techniques. Absorption and emission spectra have been collected in the presence of various anions and the selective response in dimethylsulfoxide against CN- anion has been realized. Limit of detection (LOD) of probe molecule for CN- anions has been calculated as 1.54 μM showing that the molecule could be used as a successful cyanide probe.
Seda Çınar· Journal of Apitherapy and Na...· 0 citations
This study investigates structure-property and structure-limitation relationships in a series of newly synthesised low-molecular-weight acylhydrazone derivatives obtained via ultrasonic-assisted condensation of heterocyclic aldehydes (pyrimidine, morpholine, and imidazole derivatives) with 4-methyl-1,2,3-thiadiazole-5-carboxylic acid hydrazide and 4-hydroxybenzhydrazide. The primary objective was to determine how structural variation within the heterocyclic and acyl fragments influences optical, electrochemical, thermal, and aggregation behaviour. Electrochemical studies revealed a single irreversible reduction process, mainly associated with the electron-withdrawing fragment, with LUMO orbital localization on the thiadiazole or hydrazone linkage, as supported by theoretical calculations. UV-Vis absorption maxima were largely solvent-independent across seven solvents of varying polarity. All compounds exhibited blue emission, except for the molecule containing the morpholine-thiadiazole derivative. However, the fluorescence quantum yields were low (Φ ≤ 4.1%), constituting a major photophysical limitation. Metal-complexation experiments showed weak optical responses to the tested metal cations, indicating limited binding affinity. Aggregation studies showed divergent behaviour depending on molecular structure, including aggregation-enhanced emission in the pyrimidine-thiadiazole derivative. Overall, the results demonstrate that although structural modification modulates electronic distribution and aggregation behaviour, the low emission efficiency and weak metal coordination significantly limit the potential of these materials for sensing or imaging applications.
S. Kotowicz, M. Korzec, Jan Grzegorz Małecki et al.· Chemistry· 0 citations
AIMS
To synthesize and evaluate a series of thiosemicarbazone derivatives (2a-2g) incorporating thiophene-2-carboxylic acid as urease inhibitors.
MATERIALS AND METHODS
The compounds were synthesized and characterized using modern spectroscopic techniques. In vitro urease inhibition was determined followed by computational analysis including docking, density functional theory (DFT), molecular dynamics simulations (MD), normal mode analysis (NMA), and SwissADME profiling. Compounds 2g, 2d, and 2b emerged as potent inhibitors with IC50 values of 5.48 ± 0.18 to 9.44 ± 0.32 µM, outperforming the reference thiourea (IC50 = 22.13 ± 2.82 µM). Structure-Activity Relationship (SAR) analysis revealed that electron-withdrawing nitro substituents at para positions dramatically enhanced inhibitory potency. Docking investigation demonstrated robust interactions with the urease active site that includes binuclear nickel center and residues His492, His519, and Asp633. DFT calculations established strong correlations between chemical reactivity indices and biological activity. Molecular docking and MD simulations validated stable binding interactions with key residues (His492, His519, and Asp633). NMA revealed enhanced flap flexibility (λ1 = 1.39 × 10-6) and motional coupling upon 2g binding.
CONCLUSION
These results expose the synthesized compounds, especially 2g as a potent urease inhibitor and provide a valuable insight for future anti-urease drug development.
W. Khan, Laiba, Imtiaz Ahmad et al.· Future Medicinal Chemistry· 0 citations
Due to arising of problem of antimicrobial resistance now a days, it is the requirement to develop novel antimicrobial agents. In the present research work we reported the preparation of macrocyclic divalent transition metal complexes by adopting the path of template methodology. The bivalent 3d-transition metal salts used are CoII, NiII , CuII and ZnII in their chloride form. The macrocyclic ligand is derived in situ by the help of 3,4-Diaminotoluene and Thiobarbituric acid. The synthesised complexes were fully characterised and analysed by the assistance of spectroscopic and physico-analytical techniques like IR, NMR, Electronic spectra, Electron Spray Ionisation-Mass Spectrometry, Electron Spin Resonance, CHN, Molar conductance and magnetic moment measurements. The selected analyses reveal that the macrocyclic complexes may be verbalized as [MLX2], where M is the divalent transition metal ion, L is the macrocyclic ligand and X is the counter ion of the metal salt. The Infra red spectral studies help in the primary identification for the successful development of macrocyclic complexes by the condensation reaction. The monomeric behaviour of the prepared compounds were explicated by the Mass Spectrometric and elemental analysis data. The geometry proposed was distorted octahedral in nature for all the metal complexes on the basis of results obtained from the Electronic spectra and ESR studies. Lower values of the molar conductance points in the direction of the non-electrolytic expression of the complexes. All the synthesised metal complexes were unveiled for their antifungal and antibacterial efficacies contrary to some fungal and bacterial strains. In addition to this, we have also performed the in silico ADME studies for the determination of various pharmacokinetic parameters that help in interpreting the dug like properties in the complexes.
Prachi Choudhary, Taneesha Rathee, Chandrika Malik et al.· Indian Journal of Biochemist...· 0 citations
Aiming to resolve the issues resulting from the widespread use of antifungal in agricultural production, a series of novel Pyrazole-Amides-Azobenzenes (PAAs) has been designed and synthesized by incorporating the photochromic azobenzene moiety into the pharmacophore, endowing them with both antifungal and photoswitching properties. The majority of compounds (especially target compounds A3 and A4) achieved visible light-induced transition from the trans-isomer to cis-isomer. In addition, the in vitro inhibitory activity of compound A3 against Phytophthora capsici increased from an initial 64.2% (trans-isomer) to 89.2% (cis-isomer enriched) with irradiation of 410 nm light. Following the combined enzyme inhibition assays, molecular docking simulations, and molecular dynamics simulation (MD) indicate that these compounds function as ligands targeting succinate dehydrogenase (SDH), exhibiting pronounced differences in enzyme inhibition efficacy between the cis- and trans-isomers. Notably, compounds A3 and A4 exhibited moderate SDH inhibition and low toxicity (against HK-2) in the absence of light irradiation, whereas their inhibitory activity against SDH and toxicity (against HK-2) were significantly enhanced upon irradiation at 410 nm. In addition, zebrafish embryo hatching research have demonstrated that both the trans and cis isomers of compound A4 exhibit low toxicity. Consequently, this light-controlled pharmacological behavior provides practical evidence supporting the application of the PAAs scaffold as a targeted succinate dehydrogenase inhibitor (SDHI) in agricultural production.
Hao-Ran Hu, Wen-Bin Tang, Jia-Yun Li et al.· Bioorganic chemistry (Print)· 0 citations
Enzymatic browning mediated by polyphenol oxidase (PPO) remains a persistent challenge in food preservation. We report the rational design, synthesis, and evaluation of nine coumarin-sulfonamide hybrid inhibitors (DS1-9) featuring 6,7-dihydroxy-2-oxo-2H-chromen-4-yl cores linked to N-substituted benzenesulfonamide scaffolds, confirmed by FT-IR and 1H-NMR. Enzyme kinetics against Agaricus bisporus tyrosinase revealed competitive inhibition across the series, with Ki values spanning 46-775 uM. DFT calculations (B3LYP/def2-TZVP) characterized the electronic landscape, HOMO-LUMO energies (-5.716 to -6.455 eV; -1.716 to -2.278 eV), electrophilicity indices (3.5-4.2 eV), and dipole moments (4.98-11.24 Debye), while C-PCM solvation modeling, MEP mapping, and RDG analysis established that intramolecular hydrogen bonding (sign λ2ρ ≈ -0.025 to -0.035 a.u.) preorganizes binding-competent conformations. Molecular docking against PPO3 (PDB: 2Y9X) yielded binding affinities of -7.66 to -8.99 kcal/mol, substantially exceeding tropolone (-4.65 kcal/mol). DS-7 (N-3,4-dimethylisoxazol-5-yl) emerged as the lead compound (IC50 = 103 ± 5.64 µM; Ki = 46 uM), its potency driven by hydrogen bonding with Glu322, His85, and Asn260 alongside π-sigma/π-anion contacts. DS-1 (N-thiazol-2-yl; IC50 = 99.7 ± 0.91 µM; Ki = 57 uM) achieved comparable inhibition through a distinctive π-sulfur interaction with His85 and copper coordination. DS-6 (N-ethyl-N-phenyl; IC50 = 90.3 ± 4.86 µM; Ki = 129 uM) outperformed docking predictions via apparent induced-fit binding involving dual copper π-alkyl coordination. SAR analysis identified the 6,7-dihydroxycoumarin core, Val283 π-sigma anchoring, and lipophilic N-substitution as non-negotiable pharmacophoric elements, positioning DS-7, DS-1, and DS-6 for food preservation and biocatalytic applications.
Şeref Karadeniz, Ahmad Badreddin Musatat, Beste Karadeniz et al.· Biotechnology and applied bi...· 0 citations