The current global pandemic crisis caused by the outbreak of the SARS-CoV-2 virus has caused more than 0.7 million deaths worldwide and forcing social distancing among the people affecting the...
Iron(III)-phenolate/carboxylate complexes
exhibiting photoredox
chemistry and photoactivated reactive oxygen species (ROS) generation
at their ligand-to-metal charge-transfer (LMCT) bands have emerged
as potential strategic tools for photoactivated chemotherapy. Herein,
the synthesis, in-depth characterization, photochemical assays, and
remarkable red light-induced photocytotoxicities in adenocarcinomic
human immortalized human keratinocytes (HaCaT) and alveolar basal
epithelial (A549) cells of iron(III)-phenolate/carboxylate complex
of molecular formula, [Fe(L1)(L2)] (1), where L1 is bis(3,5 di-tert-butyl-2-hydroxybenzyl)glycine
and L2 is 5-(1,2-dithiolan-3-yl)-N-(1,10-phenanthroline-5-yl)pentanamide,
and the gold nanocomposite functionalized with complex 1 (1-AuNPs) are reported. There was a significant red
shift in the UV–visible absorption band on functionalization
of complex 1 to the gold nanoparticles (λmax: 573 nm, 1; λmax: 660 nm, 1-AuNPs), rendering the nanocomposite an ideal candidate for photochemotherapeutic
applications. The notable findings in our present studies are (i)
the remarkable cytotoxicity of the nanocomposite (1-AuNPs)
to A549 (IC50: 0.006 μM) and HaCaT (IC50: 0.0075 μM) cells in red light (600–720 nm, 30 J/cm2) while almost nontoxic (IC50 > 500 μg/mL,
0.053 μM) in the dark, (ii) the nontoxicity of 1-AuNPs to normal human diploid fibroblasts (WI-38) or human peripheral
lung epithelial (HPL1D) cells (IC50 > 500 μg/mL,
0.053 μM) both in the dark and red light signifying the target-specific
anticancer activity of the nanocomposite, (iii) localization of 1-AuNPs in mitochondria and partly nucleus, (iv) remarkable
red light-induced generation of reactive oxygen species (ROS: 1O2, •OH) in vitro, (v) disruption
of the mitochondrial membrane due to enhanced oxidative stress, and
(vi) caspase 3/7-dependent apoptosis. A similar cytotoxic profile
of complex 1 was another key finding of our studies.
Overall, our current investigations show a new red light-absorbing
iron(III)-phenolate/carboxylate complex-functionalized gold nanocomposite
(1-AuNPs) as the emerging next-generation iron-based
photochemotherapeutic agent for targeted cancer treatment modality.
The earth has witnessed the greatest global health crisis due to the outbreak of the SARS‐CoV‐2 virus in late 2019, resulting in the pandemic COVID‐19 with 3.38 million mortality and 163 million infections across 222 nations. Therefore, there is an urgent need for an effective therapeutic option against the SARS‐CoV‐2 virus. Transition metal complexes with unique chemical, kinetic and thermodynamic properties have recently emerged as the viable alternative for medicinal applications. Herein, the potential application of selected antiviral transition metal‐based compounds against the SARS‐CoV‐2 virus was explored in silico. Initially, the transition metal‐based antiviral compounds (1‐5) were identified based on the structural similarity of the viral proteins (proteases, reverse transcriptase, envelop glycoproteins, etc.) of HIV, HCV, or Influenza virus with the proteins (S‐protein, RNA‐dependent RNA polymerase, proteases, etc) of SARS‐CoV‐2 virus. Hence the complexes (1‐5) were subjected to ADME analysis for toxicology and pharmacokinetics report and further for the molecular docking calculations, selectively with the viral proteins of the SARS‐CoV‐2 virus. The molecular docking studies revealed that the iron‐porphyrin complex (1) and antimalarial drug, ferroquine (2) could be the potential inhibitors of Main protease (Mpro) and spike proteins respectively of SARS‐CoV‐2 virus. The complex 1 exhibited high binding energy of −11.74 kcal/mol with the Mpro of SARS‐CoV‐2. Similarly ferroquine exhibitred binding energy of −7.43 kcal/mol against spike protein of SARS‐CoV‐2. The complex 5 also exhibited good binding constants values of −7.67, −8.68 and −7.82 kcal/mol with the spike protein, Mpro and RNA dependent RNA polymerase (RdRp) proteins respectively. Overall, transition metal complexes could provide an alternative and viable therapeutic solution for COVID‐19.
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