Nickel Complexes Bearing ONS Chelating Ligands: A Promising Contender for In Vitro Cytotoxicity Effects on Human Pancreatic Cancer MIA-PaCa‑2 Cells

The highly chronic human pancreatic cancer cell is one of the major reasons for cancerous death. Nickel complexes are recently gaining interest in anticancer activities on different types of cancer cells. Hence, in this study, we synthesized and characterized a series of ONS donor ligands [2-HO–C6H4–CHN–(C6H4)–SH] (L1), [2-OH-3-OMe–C6H3–CHN–(C6H4)–SH] (L2), [2-OH-3,5-(C(Me)3)2–C6H2–CHN–(C6H4)–SH] (L3), [2-OH–C6H4–CHN–(C6H4)–SMe] (L4), [2-OH-3-OMe–C6H3–CHN–(C6H4)–SMe] (L5), [2-OH-3,5-(C(Me)3)2–C6H2–CHN–(C6H4)–SMe] (L6) and their Ni(II) metal complexes [(MeOH)Ni(L1–L1–4H)] (1), [(MeOH)Ni(L2–L2–4H)] (2), [(MeOH)Ni(L3–L3–4H)] (3), [(L4–H)2Ni] (4), [(L5–H)2Ni] (5), and [(L6–H)2Ni] (6). The single-crystal X-ray diffraction data of complexes 1 and 4 were collected to elucidate the geometry around the metal center. The anticancer activity of complexes 1–6 was investigated on human pancreatic cancer cell line MIA-PaCa-2, which revealed that complexes 4 and 6 were the most significantly effective in decreasing the cell viability of cancer cells at the lowest dose. The structure parameters obtained from single-crystal X-ray diffraction data are found to be in good agreement with the data from density functional theory and Hirshfeld surface analysis for complex 1

Nickel Complexes Bearing ONS Chelating Ligands: A Promising Contender for In Vitro Cytotoxicity Effects on Human Pancreatic Cancer MIA-PaCa‑2 Cells

The highly chronic human pancreatic cancer cell is one of the major reasons for cancerous death. Nickel complexes are recently gaining interest in anticancer activities on different types of cancer cells. Hence, in this study, we synthesized and characterized a series of ONS donor ligands [2-HO–C6H4–CHN–(C6H4)–SH] (L1), [2-OH-3-OMe–C6H3–CHN–(C6H4)–SH] (L2), [2-OH-3,5-(C(Me)3)2–C6H2–CHN–(C6H4)–SH] (L3), [2-OH–C6H4–CHN–(C6H4)–SMe] (L4), [2-OH-3-OMe–C6H3–CHN–(C6H4)–SMe] (L5), [2-OH-3,5-(C(Me)3)2–C6H2–CHN–(C6H4)–SMe] (L6) and their Ni(II) metal complexes [(MeOH)Ni(L1–L1–4H)] (1), [(MeOH)Ni(L2–L2–4H)] (2), [(MeOH)Ni(L3–L3–4H)] (3), [(L4–H)2Ni] (4), [(L5–H)2Ni] (5), and [(L6–H)2Ni] (6). The single-crystal X-ray diffraction data of complexes 1 and 4 were collected to elucidate the geometry around the metal center. The anticancer activity of complexes 1–6 was investigated on human pancreatic cancer cell line MIA-PaCa-2, which revealed that complexes 4 and 6 were the most significantly effective in decreasing the cell viability of cancer cells at the lowest dose. The structure parameters obtained from single-crystal X-ray diffraction data are found to be in good agreement with the data from density functional theory and Hirshfeld surface analysis for complex 1

Effect of CH/P Exchange on the Fluxional Behavior of Bullvalene, Semibullvalene, and Barbaralane: A DFT Investigation

<div><p>GRAPHICAL ABSTRACT</p><p></p></div

Additional file 1 of Appraising LaQshya’s potential in measuring quality of care for mothers and newborns: a comprehensive review of India’s Labor Room Quality Improvement Initiative

Supplementary Material

VGCC activation and mycobacterial infection synergistically regulate phagosome-lysosome fusion in macrophages.

<p>PMA treated THP1 macrophages (Panel A) and mouse bone marrow derived macrophages (Panel B) were seeded on the coverslip and washed with RPMI 1640 medium and incubated in OPTIMEM medium with or without BAYK8644 for 1 h followed by infection with FM4-64 labeled <i>M</i>. <i>bovis</i> BCG (panel A) or GFP expressing <i>M</i>. <i>tb</i> H37Rv (Panel B) for 4 h. thirty minutes prior to the end of infection period, cells were incubated with 50nM of Lysotracker Green (for Panel A) or Lysotracker Green (for Panel B). At the end of incubation period cells were washed once with PBS and fixed with 4% paraformaldehyde for 1h. Following through washes, the cover slips were mounted with anti-fade containing DAPI. Confocal microscopy was performed on Leica TCS SP-8 confocal instrument, LAX Version 1.8.1.137. Bar chart in both Panel A and Panel B represents percentage of co-localization as determined by LAS AF Version 2.6.0 build 7266 of Leica Micro Systems CMS GmbH. Bars represent percentage of co-localization of the indicated groups of three independent experiments (n = 3). The stars represent the P value between unstimulated and corresponding stimulated (Bay/Amlodipine) group of that bar in each panel. The results were analyzed by one way ANOVA followed by Tukey’s post hoc multiple comparison test. * = P<u><</u> 0.05; ** = P<u><</u>0.01; *** = P<u><</u>0.001 and **** = P<u><</u>0.0001.</p

VGCC activation and mycobacterial infection synergistically lead to suppression of pro-inflammatory cytokine responses in human macrophages.

<p>Human PBMC derived macrophages (Panel A&B) either were infected with 2 MOI <i>M</i>. <i>bovis</i> BCG or stimulated with 50 nM BAYK8644 or both for 24 h. For Panel A, culture supernatant was processed for the estimation of indicated cytokines and bars represent the amount of cytokine in pg/ml. For Panel B, cells were processed for measuring surface densities of indicated cytokine receptors by FACS and bars represent MFI of indicated groups of three independent experiments (n = 3). The results were analyzed by one way ANOVA followed by Tukey’s post hoc multiple comparison test. The star above the bar represents the P value between unstimulated/uninfected and the corresponding group of that bar in each panel. ns = P>0.05; * = P<u><</u> 0.05; ** = P<u><</u>0.01; *** = P<u><</u>0.001 and **** = P<u><</u>0.0001.</p

Calcium, MAP-ERK and PKC modulate ROS generation during infection and VGCC activation.

<p>PMA stimulated THP1 macrophages were treated with inhibitors to indicated molecules for 1 h followed by either infection with 2 MOI <i>M</i>. <i>bovis</i> BCG or stimulation with 50 nM BAYK8644 or both for 1 h. In all the panels, thin line represents ROS generation in unstimulated/uninfected or control cells. Dotted line represent ROS generation in cells infected with <i>M</i>. <i>bovis</i> BCG (Panel A) or stimulation with BAYK8644 (Panel B) or both (Panel C). The thick line in all the panels represent ROS generation in cells either infected with <i>M</i>. <i>bovis</i> BCG (Panel A) or stimulated with BAYK8644 (Panel B) or both (Panel C) following treatment with inhibitors to indicated molecules. Bar graph below each panel represents MFI of the peak at the higher fluorescence in the figure. Data from one of three independent experiments are shown (n = 3). The star above the bar represents the P value between stimulated/infected cells and the corresponding group of that bar chart in each panel. The results were analyzed by one way ANOVA followed by Tukey’s post hoc multiple comparison test. ns = P > 0.05; * = P ≤ 0.05; ** = P ≤ 0.01; *** = P ≤ 0.001 and **** = P ≤ 0.0001.</p

TLR intermediates regulate ROS generation during infection and VGCC activation.

<p>PMA simulated THP1 cells were transfected with siRNAs against indicated molecules for 36 h followed by infection with 2 MOI <i>M</i>. <i>bovis</i> BCG (Panel A) and/or stimulation with 50 nM BAYK8644 (Panel B) or both (Panel C) for 1 h and ROS was estimated as described above. In all the panels, thin line represents ROS generation in unstimulated/uninfected or control cells transfected with control siRNAs. Dotted line represent ROS generation in cells transfected with control siRNA followed by either infection with <i>M</i>. <i>bovis</i> BCG (Panel A) or stimulation with BAYK8644 (Panel B) or both (Panel C). The thick line in all the panels represents ROS generation in cells either infected with <i>M</i>. <i>bovis</i> BCG (Panel A) or stimulation with BAYK8644 (Panel B) or both (Panel C) following transfection with specific siRNAs against indicated molecules. Bar graph below each panel represents MFI of the peak at the higher fluorescence in the figure. Data from one of three independent experiments are shown (n = 3). The star above the bar represents the P value between stimulated/infected groups transfected with control siRNAs and the corresponding group of that bar in each panel. The results were analyzed by one way ANOVA followed by Tukey’s post hoc multiple comparison test. ns = P > 0.05; * = P ≤ 0.05; ** = P ≤ 0.01; *** = P ≤ 0.001 and **** = P ≤ 0.0001.</p

VGCC activation and mycobacterial infection synergistically lead to suppression of pro-inflammatory cytokine responses in human macrophages.

<p>Human PBMC derived macrophages (Panel A&B) either were infected with 2 MOI <i>M</i>. <i>bovis</i> BCG or stimulated with 50 nM BAYK8644 or both for 24 h. For Panel A, culture supernatant was processed for the estimation of indicated cytokines and bars represent the amount of cytokine in pg/ml. For Panel B, cells were processed for measuring surface densities of indicated cytokine receptors by FACS and bars represent MFI of indicated groups of three independent experiments (n = 3). The results were analyzed by one way ANOVA followed by Tukey’s post hoc multiple comparison test. The star above the bar represents the P value between unstimulated/uninfected and the corresponding group of that bar in each panel. ns = P>0.05; * = P<u><</u> 0.05; ** = P<u><</u>0.01; *** = P<u><</u>0.001 and **** = P<u><</u>0.0001.</p

Activation of VGCC along with <i>M</i>. <i>bovis BCG</i> infection attenuates ROS in mouse and human macrophages.

<p>For Panel A, macrophages were derived from bone marrow of female Balb/c mice. For Panel B, PBMCs from healthy volunteers were differentiated into macrophages. Macrophages were either infected with 2 MOI <i>M</i>. <i>bovis</i> BCG or stimulated with 50 nM BAYK8644 or both for 1h and ROS was estimated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163845#pone.0163845.g001" target="_blank">Fig 1</a>. In both the Panels, thin line represents ROS generation in uninfected or unstimulated or control cells; thick line represents ROS generation in infected or stimulated cells as indicated. Bar chart below each panel represents MFI of the peak at the higher fluorescence in the figure. Data from one of three independent experiments are shown (n = 3). The star above the bar represents the P value between control and the corresponding group of that bar in each panel. The results were analyzed by one way ANOVA followed by Tukey’s post hoc multiple comparison test. * = P ≤ 0.05; ** = P ≤ 0.01; *** = P ≤ 0.001 and **** = P ≤ 0.0001.</p