PMID- 32589180 OWN - NLM STAT- MEDLINE DCOM- 20210426 LR - 20210426 IS - 1477-9234 (Electronic) IS - 1477-9226 (Linking) VI - 49 IP - 27 DP - 2020 Jul 17 TI - Thiosemicarbazone(s)-anchored water soluble mono- and bimetallic Cu(ii) complexes: enzyme-like activities, biomolecular interactions, anticancer property and real-time live cytotoxicity. PG - 9411-9424 LID - 10.1039/d0dt01309a [doi] AB - The reactions of CuCl2.2H2O with chromone thiosemicarbazone ligands containing a -H or -CH3 substituent on terminal N yielded monometallic Cu(ii) complexes [Cu(HL1)Cl2] (1) and [Cu(HL2)Cl2] (2), whereas bimetallic Cu(ii) complexes [Cu(mu-Cl)(HL3)]2Cl2 (3), [Cu(mu-Cl)(HL4)]2Cl2 (4) and [Cu(mu-Cl)(L5)]2 (5) were obtained when a -C2H5, -C6H11 or -C6H5 substituent was present, respectively, in the ligands. The complexes were characterized using elemental analyses, UV-Vis, FT-IR, EPR, mass and TGA studies. The structures of neutral monometallic and dicationic bimetallic complexes were confirmed by single crystal X-ray diffraction, and they exhibited a distorted square pyramidal geometry around Cu(ii) ions. The catecholase-mimicking activity of complexes 1-5 was examined spectrophotometrically, and the results revealed that all the complexes except 5 had the ability to oxidize 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylquinone (3,5-DTBQ) under aerobic conditions with moderate turnover numbers. In order to find the possible complex-substrate intermediates, a mass spectrometry study was carried out for complexes 1-4 in the presence of 3,5-DTBC. The phosphatase-like activity of 1-5 was also investigated using 4-nitrophenylphosphate (4-NPP) as a model substrate. All the complexes exhibited excellent phosphatase activity in DMF-H2O medium. The complexes displayed significant biomolecular interactions and antioxidant potential. Complex 3 showed good interaction with apoptotic CASP3 protein, VEGFR2 and PIM-1 kinase receptors as revealed by a molecular docking study. Complexes (3-5) exhibited promising cytotoxicity against HeLa-cervical cancer cells with IC50 values of 2.24 (3), 2.25 (4) and 3.77 (5) muM, respectively, and showed a two-fold higher activity than cisplatin. The active complex 3 showed complete inhibition of colony formation at 10 muM concentration. In addition, the acridine orange (AO)/ethidium bromide (EB) staining and real-time live cell imaging results confirmed that complex 3 induced cell death in HeLa cells. FAU - Balakrishnan, Nithya AU - Balakrishnan N AD - Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India. kar@nitt.edu. FAU - Haribabu, Jebiti AU - Haribabu J AD - Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India. kar@nitt.edu and Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan. FAU - Dhanabalan, Ananda Krishnan AU - Dhanabalan AK AD - Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India. FAU - Swaminathan, Srividya AU - Swaminathan S AD - Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India. kar@nitt.edu. FAU - Sun, Sijia AU - Sun S AD - Division of Natural Drug Discovery, Department of Translational Research, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. FAU - Dibwe, Dya Fita AU - Dibwe DF AD - Division of Natural Drug Discovery, Department of Translational Research, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. FAU - Bhuvanesh, Nattamai AU - Bhuvanesh N AD - Department of Chemistry, Texas A & M University, College Station, TX 77842, USA. FAU - Awale, Suresh AU - Awale S AUID- ORCID: 0000-0002-5299-193X AD - Division of Natural Drug Discovery, Department of Translational Research, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. FAU - Karvembu, Ramasamy AU - Karvembu R AUID- ORCID: 0000-0001-8966-8602 AD - Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India. kar@nitt.edu. LA - eng PT - Journal Article PL - England TA - Dalton Trans JT - Dalton transactions (Cambridge, England : 2003) JID - 101176026 RN - 0 (Antineoplastic Agents) RN - 0 (Catechols) RN - 0 (Coordination Complexes) RN - 0 (Phosphates) RN - 0 (Thiosemicarbazones) RN - 789U1901C5 (Copper) RN - 9007-49-2 (DNA) RN - EC 2.7.10.1 (KDR protein, human) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) RN - EC 2.7.11.1 (PIM1 protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - LF3AJ089DQ (catechol) SB - IM MH - Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology MH - Caspase 3/chemistry MH - Catechols/chemistry MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Coordination Complexes/chemical synthesis/chemistry/*pharmacology MH - Copper/chemistry/*pharmacology MH - DNA/chemistry MH - Drug Screening Assays, Antitumor MH - Humans MH - Hydrolysis MH - Molecular Docking Simulation MH - Molecular Structure MH - Optical Imaging MH - Oxidation-Reduction MH - Phosphates/chemistry MH - Proto-Oncogene Proteins c-pim-1/chemistry MH - Thiosemicarbazones/chemistry/*pharmacology MH - Time Factors MH - Vascular Endothelial Growth Factor Receptor-2/chemistry EDAT- 2020/06/27 06:00 MHDA- 2021/04/27 06:00 CRDT- 2020/06/27 06:00 PHST- 2020/06/27 06:00 [pubmed] PHST- 2021/04/27 06:00 [medline] PHST- 2020/06/27 06:00 [entrez] AID - 10.1039/d0dt01309a [doi] PST - ppublish SO - Dalton Trans. 2020 Jul 17;49(27):9411-9424. doi: 10.1039/d0dt01309a.