Synthesis, characterization, cytotoxicity evaluation, and molecular docking with DNA, bovine serum albumin, and SARS-Cov-2 of copper complexes bearing tris-(2-pyridyl)-pyrazolyl borate ligand

Four copper (II) complexes bearing tris-(2-pyridyl)-pyrazolyl borate (Tppy) ligand with corresponding chloride (Cu-1), aqua (Cu-2), azide (Cu-3), and thiocyanide (Cu-4) substitutions were synthesized and characterized by spectroscopic and analytical methods. Spectroscopic and molecular docking studies were employed to investigate the interactions of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA). The results inferred intercalation binding mode of the complexes with DNA. All the complexes exhibited good binding with BSA as well. In addition, the binding efficacy of the Cu (II) complexes with SARS-Cov-2 was tested in silico. Further, in vitro anticancer activity of the complexes was investigated against the HeLa-cervical, HepG2-liver and A549-lung cancer, and one normal (L929-fibroblast) cell line. IC50 values unveiled that the complexes were more active than cisplatin against all three cancer cells. It was understood that complex Cu-3 containing azide substitution displayed the highest activity on the HeLa cell line (IC50 = 6.3 μM). More importantly, TppyCu (II) complexes were not active against the normal cell line. Lastly, the acridine orange/ethidium bromide (AO/EB) and 4′,6-diamidino-2-phenylindole staining assays indicated that Cu-3 induced cell death in HeLa cells at the late apoptotic stage. This complex also efficiently generated ROS in HeLa cells promoting apoptosis as understood from the DCFH-DA assay. © 2023 John Wiley & Sons, Ltd.

In silico identification of a potent arsenic based lead drug di-phenyl phenoxy roxarsone against SARS-CoV-2

In this article we have tried to address the plausible identification of a novel lead drug molecule against COVID-19. Nine different arsenic (As) based molecules, roxarsone derivatives were designed and optimized for computational analysis to determine its binding affinity against SARS-CoV-2. The molecules were screened based on their chemical reactivity with respect to conceptual density functional theory (CDFT) and global reactivity descriptors. The screened molecules were docked blindly against RNA dependent RNA polymerase (RdRp) using molecular docking software iGEMDOCK v2.1. On the basis of idock score in their respective catalytic domain, di-phenyl phenoxy roxarsone identified as promising inhibitor against SARS-CoV-2 with binding free energy calculated as -86.8 kcal/mol. Site specific docking was also executed with target site, receptor binding domain (RDB) of spike glycoprotein of SARS-CoV-2 whose structure was computationally designed using Phyre2 server. The interaction study of RDB with di-phenyl phenoxy roxarsone revealed a binding energy -133.3 kcal/mol. Thus it can be concluded from the above in silico experiment that screening of potential arsenic based roxarsone derivative would help in development of new therapeutic drug for COVID-19. © 2020 Scientific Publishers. All rights reserved.