Your browser doesn't support javascript.
Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2.
Haribabu, Jebiti; Srividya, Swaminathan; Mahendiran, Dharmasivam; Gayathri, Dasararaju; Venkatramu, Vemula; Bhuvanesh, Nattamai; Karvembu, Ramasamy.
  • Haribabu J; Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.
  • Srividya S; Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.
  • Mahendiran D; Department of Pathology, Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
  • Gayathri D; Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India.
  • Venkatramu V; Department of Physics, Krishna University Dr. MRAR PG Centre, Nuzvid 521201, India.
  • Bhuvanesh N; Department of Chemistry, Texas A & M University, College Station, Texas 77842, United States.
  • Karvembu R; Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.
Inorg Chem ; 59(23): 17109-17122, 2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-1387106
ABSTRACT
Metal complexes have numerous applications in the current era, particularly in the field of pharmaceutical chemistry and catalysis. A novel synthetic approach for the same is always a beneficial addition to the literature. Henceforth, for the first time, we report the formation of three new Pd(II) complexes through the Michael addition pathway. Three chromone-based thiosemicarbazone ligands (SVSL1-SVSL3) and Pd(II) complexes (1-3) were synthesized and characterized by analytical and spectroscopic tools. The Michael addition pathway for the formation of complexes was confirmed by spectroscopic studies. Distorted square planar structure of complex 2 was confirmed by single-crystal X-ray diffraction. Complexes 1-3 were subjected to DNA- and BSA-binding studies. The complex with cyclohexyl substituent on the terminal N of thiosemicarbazone (3) showed the highest binding efficacy toward these biomolecules, which was further understood through molecular docking studies. The anticancer potential of these complexes was studied preliminarily by using MTT assay in cancer and normal cell lines along with the benchmark drugs (cisplatin, carboplatin, and gemcitabine). It was found that complex 3 was highly toxic toward MDA-MB-231 and AsPC-1 cancer cells with IC50 values of 0.5 and 0.9 µM, respectively, and was more efficient than the standard drugs. The programmed cell death mechanism of the complexes in MDA-MB-231 cancer cells was confirmed. Furthermore, the complexes induced apoptosis via ROS-mediated mitochondrial signaling pathway. Conveniently, all the complexes showed less toxicity (≥50 µM) against MCF-10a normal cell line. Molecular docking studies were performed with VEGFR2, EGFR, and SARS-CoV-2 main protease to illustrate the binding efficiency of the complexes with these receptors. To our surprise, binding potential of the complexes with SARS-CoV-2 main protease was higher than that with chloroquine and hydroxychloroquine.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Reactive Oxygen Species / Apoptosis / Coordination Complexes / SARS-CoV-2 / Mitochondria / Antineoplastic Agents Type of study: Experimental Studies Limits: Humans Language: English Journal: Inorg Chem Year: 2020 Document Type: Article Affiliation country: ACS.INORGCHEM.0C02373

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Reactive Oxygen Species / Apoptosis / Coordination Complexes / SARS-CoV-2 / Mitochondria / Antineoplastic Agents Type of study: Experimental Studies Limits: Humans Language: English Journal: Inorg Chem Year: 2020 Document Type: Article Affiliation country: ACS.INORGCHEM.0C02373