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

Severalspecies,suchasbacteria,fungi,fish,andinsects,producelightthroughbiochemicalpro-cesses.FireflyD-luciferinhasbeenstudiedextensivelysinceitpossessesbothahighquantumyieldandawide emissionwavelength. Five transition metal complexes of D-luciferin (LN)withMn(II), Co(II),Ni(II), Cu (II)andZn(II)weresynthesizedusinga 1:2metaltoligandratio. Thestructureofthesynthesized complexes wasconfirmedutilizingspectroscopictechniques(FTIR,1HNMR,EPR,andUV-Vis),elementalanalysis, 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 oftheligand and its complexes. The results revealed thatluciferinisbidentatelycou-pledto therelevantmetalsineachofthesecomplexesthroughtwosulfuratomsofthiazolerings. Molar con-ductance values showed the non-electrolytic character of the synthesized complexes. Diverse techniques wereemployedtoexaminethecomplexes'bindingaffinitytocalfthymusDNA,includingUV-Vis,fluores-cence,viscosity measurements andmoleculardocking. The results revealed that they bind non-covalently withDNAviagroovebinding.Furthermore,theinteractionofthesecomplexeswithhumanserumalbumin (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 moleculardockingstudies. Finally,humanhepatocellularcarcinomacellline(HepG-2)andhuman breast cancer cell line (MCF-7) were used to investigate the cytotoxic activity of ligand and metal complexes. Among thefivesynthesizedcomplexes, [Zn(LN)2Cl2]H2Ocomplexhasthebestanticanceractivity against MCF-7andHepG-2celllineswithIC50valuesof20and37.39mM,respectively.Themoleculardockingstud-ies and in vitro cytotoxicity assay showed a significant correlation.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

Researchers synthesized five transition metal complexes of D-luciferin (LN) and studied their structures and properties. The complexes showed non-covalent binding with DNA and HSA, and exhibited significant cytotoxic activity against breast cancer and liver cancer cells.