Synthesis, structural characterization, DNA/HSA binding, molecular docking and anticancer studies of some D-Luciferin complexes

Several species, such as bacteria, fungi, fish, and insects, produce light through biochemical processes. Firefly D-luciferin has been studied extensively since it possesses both a high quantum yield and a wide emission wavelength. Five transition metal complexes of D-luciferin (LN) with Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) were synthesized using a 1:2 metal to ligand ratio. The structure of the synthesized complexes was confirmed utilizing spectroscopic techniques (FTIR, 1H NMR, EPR, and UV–Vis), elemental analysis, thermogravimetric analysis, molar conductivity, and magnetic susceptibility. Density functional theory (DFT/B3LYP) calculations were also used to confirm the structural characteristics and provide the fully optimized geometries of the ligand and its complexes. The results revealed that luciferin is bidentately coupled to the relevant metals in each of these complexes through two sulfur atoms of thiazole rings. Molar conductance values showed the non-electrolytic character of the synthesized complexes. Diverse techniques were employed to examine the complexes' binding affinity to calf thymus DNA, including UV–Vis, fluorescence, viscosity measurements and molecular docking. The results revealed that they bind non-covalently with DNA via groove binding. Furthermore, the interaction of these complexes with human serum albumin (HSA) was investigated via UV–Vis, fluorescence and molecular docking. The binding susceptibly of the complexes toward breast cancer (PDB: 3eqm) and liver cancer (PDB: 4mf9) proteins was assessed using molecular docking studies. Finally, human hepatocellular carcinoma cell line (HepG-2) and human breast cancer cell line (MCF-7) were used to investigate the cytotoxic activity of ligand and metal complexes. Among the five synthesized complexes, [Zn(LN)2Cl2]H2O complex has the best anticancer activity against MCF-7 and HepG-2 cell lines with IC50 values of 20 and 37.39 µM, respectively. The molecular docking studies and in vitro cytotoxicity assay showed a significant correlation

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population