We evaluate herein the impact of positive charge distribution on the in vitro and in vivo properties of Mn porphyrins as redox modulators possessing the same overall 5+ charge and of minimal stericity demand: Mn(III) meso-tetrakis(trimethylanilinium-4-yl)porphyrin (MnTTriMAP(5+)), Mn(III) meso-tetrakis(N,N'-dimethylpyrazolium-4-yl)porphyrin (MnTDM-4-PzP(5+)), Mn(III) meso-tetrakis(N,N'-dimethylimidazolium-2-yl)porphyrin (MnTDM-2-ImP(5+)), and the ortho and para methylpyridinium complexes Mn(III) meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (MnTM-4-PyP(5+)) and Mn(III) meso-tetrakis(N-methylpyridinium-2-yl)porphyrin (MnTM-2-PyP(5+)). Both Mn(III)/Mn(II) reduction potential and SOD activity within the series follow the order: MnTTriMAP(5+)

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Meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin sulfonate (TDMPzP), a water-soluble porphyrin derivative, was synthesized and used as a colorimetric reagent for Cu detection on a microfluidic paper-based analytical device (µPAD) using distance-based quantification. TDMPzP showed a high selectivity for Cu detection in aqueous solutions. When Cu was added to the TDMPzP under acidic conditions, a color change from green to a pink was observed by the naked eye. Under optimized conditions, the application of this system to a distance-based μPAD exhibited good analytical response. The presence of common metal ions (Al, Fe, Mg, Co, Mn, Zn, Pb, Cd, Sn, and Ni) did not interfere with Cu detection within reasonable tolerance ratios. The lowest concentration of copper that could be measured was 1mgL (1ppm) which meets the requirements for drinking water contamination regulations from the US Environmental Protection Agency (EPA) and World Health Organization (WHO) guidelines for drinking water. Real drinking water samples were analyzed to confirm the practical application of this system and the results showed good agreement with ICP-MS data. This distance-based µPAD based on TDMPzP for Cu detection is convenient and effective for real-time drinking water analysis.

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Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) play an important role in cancer growth. Both of them have close relationships. Expression of EGFR will induce an angiogenic factor (VEGF) release for binding with VEGFR2. However, the existence of VEGF up-regulation independent of EGFR leads to cancer cell resistance to anti-EGFR. Therefore, a therapeutic approach targeting EGFR and VEGFR2 simultaneously may improve the outcome of cancer treatment. The present study was designed to identify potential compounds as a dual inhibitor of EGFR and VEGFR2 by the computational method. Firstly, the ligand-based pharmacophore model for each target was setup to screen of ZINC database of purchasable compounds. The hit compounds obtained by pharmacophore screening were then further screened by molecular docking studies. Taking erlotinib (EGFR inhibitor) and axitinib (VEGFR2 inhibitor) as reference drugs, six potential compounds (ZINC08398597, ZINC12047553, ZINC16525481, ZINC17418102, ZINC21942954, and ZINC38484632) were selected based on their docking scores and binding interaction. However, molecular dynamics simulations demonstrated that only ZINC16525481 and ZINC38484632 which have good binding free energy and stable hydrogen bonding interactions with EGFR and VEGFR2. The result represents a promising starting point for developing potent dual tyrosine kinases inhibitor of EGFR and VEGFR2.

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