Browsing by Author "Ray Jay Butcher"

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Anti-metastatic cancer potential of 4H-chromene derivatives targeting JNK in Scribble knockdown induced epithelial cancer model: In vivo and in silico studies
(Academic Press Inc., 2025) Vaishali Raghuvanshi; Jyotsna Singh; Saurabh Sharma; Ray Jay Butcher; Saripella Srikrishna; Diksha Katiyar
Building on our previous work on the synthesis of a series of 4H-chromene derivatives, we report herein for the first time the in vivo and in silico studies of ten chromene derivatives 5a-j as potential anti-metastatic cancer agents targeting through c-Jun N-terminal kinase (JNK). Compounds 5a-j were resynthesized using the protocol previously reported by our research group. Out of these, 5c, 5f-h and 5j showed good anti-metastatic cancer activity in Drosophila in vivo model, with 5f being the most active. It exhibited 27% rescue in metastatic cancer induced pupal lethality, whereas the standard drug sorafenib showed no rescue. Furthermore, 5f has significantly downregulated JNK and the metastasis promoting marker enzyme, matrix metalloproteinase-1 (MMP1) expression in Scribble (Scrib) knockdown induced Drosophila cancer tissues. In silico studies of all the compounds, 5a-j, demonstrated strong binding affinity with Drosophila JNK protein (PDB ID: 5AWM). Additionally, comparison of the docking positions of 5f in the 5AWM and human JNKs (PDB IDs: 1UKH and 3E7O) binding sites revealed a high degree of homology between them with respect to the similar set of amino acids interacting with the ligand. Compounds 5a-j also exhibited favourable pharmacokinetic properties with drug-like characteristics, as predicted by SwissADME analysis. The crystal structure of 5f was determined for the first time using single-crystal X-ray diffraction (SC-XRD) analysis. It crystallizes in a monoclinic crystal system with the space group P21/c, providing valuable insights into its structural features and molecular arrangement. The present findings strongly suggest that the chromene derivatives, represented by compound 5f, hold promise as potential anticancer agents targeting the metastatic stage in various epithelial cell-derived cancers. © 2025 Elsevier Inc.
Anticancer activity of Co(III) complex containing mixed ligand bis(5-phenyl-1,2,4-triazole)-3-sulfinamide and o-phen: Crystal structure, DFT, and Hirshfeld surface analysis
(Elsevier B.V., 2025) Shivendra Kumar Pandey; S. Dasaratha Kumar; Riya Kumari; Arbind Acharya; Ray Jay Butcher; Manoj Kumar Bharty
The cobalt complexes have demonstrated potential as antibacterial, antifungal, and anticancer agents, further enhancing their significance in the field of medicinal chemistry. Here, a cobalt(III) complex [Co(ptsm)H2O(o-phen)]·CH3OH containing in situ formed bis(5-phenyl-1,2,4-triazole)-3-sulfinamide (ptsm), 1,10-phenanthroline, and H2O molecule as ligand along with methanol molecule as crystallized solvent has been synthesized and characterized by various spectroscopic and X-ray crystallography techniques. The cobalt complex crystallizes in a triclinic system with space group P-1. The DFT and TD-DFT calculations were also performed to optimize geometry and better understand electronic transitions. The outcomes of quantum chemical calculations (TD-DFT and DFT) match the characteristics of the experiments. Various intermolecular interactions in complex 1 have been quantitively explained with Hirshfeld surface analysis. The MTT assay assessed the cytotoxicity of complex 1 against Dalton's lymphoma (DL) cells, yielding IC50 values of 40 µM. The AO/EtBr dual staining and DAPI staining further confirm the cytotoxic potential of the complex 1. © 2024 Elsevier B.V.
Anticancer evaluation of Co(III) complex derived from 1-isonicotinoyl-4-(4-nitrophenyl)-3-thiosemicarbazide: Structural characterization, photophysical, and Hirshfeld studies
(Elsevier B.V., 2025) Ram Nayan Gautam; Alok Shukla; Suryansh Chandra; Sundeep Kumar; Arbind Acharya; Mamata K. Singh; Ray Jay Butcher; Manoj Kumar Bharty
A new cationic complex, [Co((intph)(en)2]Cl, derived from the 1-isonicotinoyl-4-(4-nitrophenyl)-3-thiosemicarbazide (H2intph), is reported. The synthesized ligand and its corresponding Co(III) complex were successfully characterized by applying FT-IR and UV–visible spectroscopic techniques and single crystal ray diffraction data. Molecular geometries of the ligand and its Co(III) complex were accurately determined from their respective X-ray crystallographic analysis. The ligand and [Co((intph)(en)2]Cl crystallize in Triclinic and monoclinic systems with space groups P-1 and P 21/n, respectively. The crystal structures of H2intph and [Co((intph)(en)2]Cl are stabilized by weak C-H⋯O, N-H⋯O, and C-H⋯Cl hydrogen bonding interactions. Hirshfeld surface analysis was accomplished to investigate intermolecular hydrogen bonding interactions found in ligand H2intph and [Co((intph)(en)2]Cl. The cytotoxicity of the ligand and the complex [Co((intph)(en)2]Cl was assessed for their anticancer potential against human glioblastoma (U87) and Dalton lymphoma (DL) cell lines. The complex exhibited IC50 values of 100 μg/mL for U87 cells and 120 μg/mL for DL cells, indicating the concentration at which 50 % of cell viability was inhibited. In comparison, the ligand was less effective in the MTT assay against both U87 and DL cells. These results suggest that the complex [Co((intph)(en)2]Cl significantly reduces glioblastoma cell viability. Treatment with the complex induced cell death through both apoptotic and necrotic pathways, as evidenced by Hoechst/PI double staining. Additionally, there was an increase in intracellular reactive oxygen species (ROS), highlighting the role of oxidative stress in the anticancer activity of the [Co((intph)(en)2]Cl complex. Furthermore, fluorescence studies were carried out which revealed the order of fluorescence behaviors between the ligand and the Co(III) complex to be Co(III) complex > H2intph. © 2024 Elsevier B.V.
Exploring the anticancer activity of 1-(2-methyl-3-furoyl)-4-phenyl-3-thiosemicarbazide and its Mn(II) complex: Synthesis, spectral, crystal structures, and Hirshfeld surface analysis
(Elsevier B.V., 2025) Rahul Chaurasia; Alok Shukla; Shivendra Kumar Pandey; Seema Gupta; Nishant Shekhar; Arbind Acharya; Ray Jay Butcher; Manoj Kumar Bharty
The chemistry of mixed ligand transition metal complexes has been of interest of researchers owing to its diverse application and bonding features. Herein, a new thiosemicarbazide derivative namely 1-(2-methyl-3-furoyl)-4-phenyl-3-thiosemicarbazide (HmfpTSC) has been synthesized along with its [Mn(mfpTSC)2(o-phen)] (C1) complex. The prepared ligand (HmfpTSC) and the complex have been confirmed via spectroscopic and single-crystal X-ray data. The HmfpTSC and complex crystallize in a monoclinic crystal system with space group P21/c and P21/n, respectively. HmfpTSC behaves as a uninegative bidentate ligand and its two-unit binds with metal ion along with one unit of o-phen. Using Hirshfeld surface analysis, the weak interactions seen in HmfpTSC and complex have been quantitatively investigated. The MTT assay was used to assess the cytotoxicity of HmfpTSC and [Mn(mfpTSC)2(o-phen)] complex against Dalton's lymphoma cells. Further, the mechanism of anticancer action of ligand and complex was investigated through DAPI, AO/EB staining, and flow cytometry. The both AO/EB and DAPI staining provided compelling evidence of complex-induced cellular and nuclear changes consistent with apoptosis and necrosis. © 2024
Exploring the synthesis, characterization, crystal structures, DFT calculation, hirshfeld surface analysis, and anticancer activity of Ni(II) complex of 1-(4-nitrobenzoyl)-4-phenyl-3-thiosemicarbazide
(Elsevier B.V., 2025) Shivendra Kumar Pandey; Rahul Chaurasia; Alok Shukla; Riya Kumari; Nishant Shekhar; Arti Srivastava; Arbind Acharya; Ray Jay Butcher; Manoj Kumar Bharty
The chemistry of biologically active thiosemicarbazide has been of interest to researchers owing to its diverse application and bonding features. In the present study, a new thiosemicarbazide derivative namely 1-(4-nitrobenzoyl)-4-phenyl-3-thiosemicarbazide (HnbphTSC) has been prepared and along with its [Ni(nbphTSC)2(en)]·CHCl3 (1) complex. The prepared ligand (HnbphTSC) and complex 1 have been characterized through spectroscopic and single-crystal X-ray data. The HnbphTSC and complex 1 crystallize in triclinic and monoclinic crystal systems with space groups P1¯ and P21/C, respectively. The weak interactions present in HnbphTSC and complex 1 have been quantitively studied through hirshfeld surface analysis. The physiochemical characteristics of HnbphTSC and complex 1 are also verified using DFT calculations, and the resultant results are in strong agreement with the experimental findings. The HOMO and LUMO energy gap have been calculated as 3.160 eV and 2.212 eV for HnbphTSC and complex 1, respectively. MTT assay was used to evaluate the cytotoxicity of HnbphTSC and complex 1 against Dalton's lymphoma (DL) cells. We further assessed the mode of tumor cell death and the drug's effect on nuclear condensation and plasma membrane integrity by employing DAPI/PI dual staining technique. © 2024 Elsevier B.V.
Structural insights and in vitro and in vivo anticancer evaluation of dithiocarbamate-based metal complexes against murine lymphoma
(Royal Society of Chemistry, 2025) Anupam Singh; Riya Patel; Samrat Daripa; Manoj Kumar Bharty; Ray Jay Butcher; Sumit K. Hira; Lal Bahadur Prasad
Metal-based chemotherapeutics have gained attention due to their ability to interfere with cellular functions. Dithiocarbamate ligands, known for their strong metal-binding properties, have been explored for their potential in anticancer applications. This study aims to synthesize and characterize dithiocarbamate-based Ni(ii), Cu(ii), and Zn(ii) complexes and evaluate their anticancer activity against Dalton's lymphoma (DL) cells. Three dithiocarbamate ligands (1-3) and their corresponding Ni(ii), Cu(ii), and Zn(ii) complexes (1a-c, 2a-c, and 3a-c) were synthesized and characterized using FT-IR, NMR, UV-Vis, and mass spectrometry, and single-crystal X-ray diffraction (SC-XRD). TGA analysis of complexes confirms their thermal stability up to 150 °C and the formation of metal sulfides at elevated temperatures. The in vitro antiproliferative activities of these compounds were assessed using the MTT assay. Apoptosis induction was analyzed via Annexin V-FITC/PI staining and flow cytometry. In vivo studies were conducted on a murine DL tumor model to evaluate therapeutic efficacy and biosafety. SC-XRD confirmed square planar geometries for Ni(ii) and Cu(ii) complexes, whereas Zn(ii) complexes exhibited a tetrahedral geometry. Metal complexes 1c, 2b, and 3c displayed the most potent antiproliferative activity, with 1c exhibiting the lowest IC50 (7.1 μM). Apoptosis analysis indicated that 1c induced 64% apoptosis in DL cells. In vivo studies demonstrated that 1c significantly reduced tumor growth and prolonged survival, with minimal toxicity. The synthesized dithiocarbamate-metal complexes exhibited promising anticancer properties, particularly 1c, which demonstrated superior efficacy in both in vitro and in vivo models. These findings highlight the potential of metal-based dithiocarbamates as novel anticancer agents warranting further preclinical studies. © 2025 The Royal Society of Chemistry.