Tuberculosis - a disease caused by Mycobacterium tuberculosis (Mtb), is one of the most devastating disease. The discovery of Ser/Thr protein kinases (STPKs) in Mtb opened a new avenue for developing anti-tubercular inhibitors. The in-vivo inhibitory effects of many metal ions have been demonstrated in literature. But, one of the limitations of metal ions as inhibitors is their inability to traverse the hydrophobic membrane due to polar nature and their propensity for non-specific interactions. To overcome this, we attached a metal ion to 2-A9P - an analog derived from a cell permeable scaffold, 2-Aminopurine (2-AP) which is a known kinase inhibitor. We investigated the inhibitory potential of 2-AP and its analog 2-A9P against protein kinase B (PknB) and showed that both of these can inhibit Mtb STPKs. Next, we evaluated the latent inhibitory activity of metal ions and for the first time showed that they can inhibit the phosphotransfer reaction in PknB, PknG and PknL. Subsequently, 6 different metal complexes (MC) of 2-A9P were used for inhibitory studies and their estimated IC values show that most MCs inhibited PknB with low micromolar potency. Further, MIC values determined for the six MCs against Mtb showed that MC-4 and MC-6 exhibit whole cell inhibitory activity. Cytotoxicity studies show that MC-4 and MC-6 do not affect cell viability of A549 cell lines, suggesting that these inhibitors can be further developed as anti-tubercular agents.
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http://dx.doi.org/10.1016/j.tube.2017.10.005 | DOI Listing |
Biochemistry
January 2025
Department of Microbiology, Cornell University, Ithaca, New York 14853-8101, United States.
Metal ions are essential for all life. In microbial cells, potassium (K) is the most abundant cation and plays a key role in maintaining osmotic balance. Magnesium (Mg) is the dominant divalent cation and is required for nucleic acid structure and as an enzyme cofactor.
View Article and Find Full Text PDFActa Crystallogr C Struct Chem
January 2025
College of Chemistry and Materials Science, Anhui Normal University, Wuhu, Anhui 241000, People's Republic of China.
A new twofold interpenetrated 3D metal-organic framework (MOF), namely, poly[[μ-aqua-diaqua{μ-2,2'-[terephthaloylbis(azanediyl)]diacetato}barium(II)] dihydrate], {[Ba(CHNO)(HO)]·2HO}, (I), has been assembled through a combination of the reaction of 2,2'-[terephthaloylbis(azanediyl)]diacetic acid (TPBA, HL) with barium hydroxide and crystallization at low temperature. In the crystal structure of (I), the nine-coordinated Ba ions are bridged by two μ-aqua ligands and two carboxylate μ-O atoms to form a 1D loop-like Ba-O chain, which, together with the other two coordinated water molecules and μ-carboxylate groups, produces a rod-like secondary building unit (SBU). The resultant 1D polynuclear SBUs are further extended into a 3D MOF via the terephthalamide moiety of the ligand as a spacer.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Chemistry Education, Seoul National University, Seoul, Republic of Korea.
In terms of safety and emergency response, identifying hazardous gaseous acid chemicals is crucial for ensuring effective evacuation and administering proper first aid. However, current studies struggle to distinguish between different acid vapors and remain in the early stages of development. In this study, we propose an on-site monitorable acid vapor decoder, MOF-808-EDTA-Cu, integrating the robust MOF-808 with Cu-EDTA, functioning as a proton-triggered colorimetric decoder that translates the anionic components of corrosive acids into visible colors.
View Article and Find Full Text PDFBiosens Bioelectron
December 2024
School of Pharmacy, Xi'an Medical University, Xi'an, 710021, China; Institute of Medicine, Xi'an Medical University, Xi'an, 710021, China. Electronic address:
In this study, a convenient method was proposed for the synthesis of thymine-capped mesoporous silica nanoparticles (MSN) using strong hydrogen bonding in non-protonic solvent. Furthermore, application of the functionalized MSN for the recognition of mercuric ion (Hg) based on a paper-based platform with smartphone-assisted colorimetric detection was developed. The synthesized materials were characterized by techniques including X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), N adsorption-desorption, particle size analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA).
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
December 2024
School of Chemistry and Chemical Engineering, Shaanxi Key Laboratory of Chemical Reaction Engineering, Laboratory of New Energy & New Function Materials, Yanan University, Yan'an 716000, China.
Elemental analysis, infrared spectroscopy, and X-ray single crystal diffraction indicated that a novel metal-organic framework (Tb-MOF) designated as 0.5n[Hbpy]·[Tb(dpa)(HO)]·4nHO was synthesized successfully, (where Hdpa = 5-(3, 4-dicarboxy- phenoxy) isophenic acid, bpy = protonated 4,4'-bipyridine). Tb-MOF adopts a 3D network structure based on Tb ions and the (dpa) ligand through µ: η, η, η, η binding modes.
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