In silico screening and molecular docking of spiroindimicin A-H targeting Insulin Growth Factor 1 Receptor (IGF-1R) for cancer treatment

Abstract

Spirocyclic compounds have the potential to become anticancer drugs, hence it is anticipated that spiroindimicin A-H, which has moderate cytotoxicity against numerous cancer cell lines, can be a promising anticancer treatment for drug discovery. Insulin-growth factor 1 receptor (IGF-1R) is currently one of the most desired targets for cancer treatments. The aim of this work is to identify spiroindimicin A-H as potential lead compounds for the development of anticancer medicines using in silico research. Spiroindimicin A-H were docked against IGF-1R using the mcule (one-click docking server) and ligPlot+ software. SwissADME, Molinspiration and ProTox II computational tools were used to predict their physicochemical, pharmacokinetic, bioactive and toxicity properties.In this work, spiroindimicin C had the highest affinity score out of all the compounds, which all displayed high affinity, with a binding energy of 9.1 kcal/mol via three hydrogen bonds (GLN24C, LYS50C and ASP165C). Although all spiroindimicin A-H adhered to the (Rule of five) Ro5 filter, they might have low bioavailability and undesirable pharmacokinetic consequences.

In Silico ADME/Tox Profiling of Mushroom Secondary Metabolites

“…Lipophilicity is a crucial factor in the development of new drugs [30,31] because it enhances medicinal chemistry‘s most effective and informative single physicochemical attribute [32] …”

“…Lipophilicity is a crucial factor in the development of new drugs [30,31] because it enhances medicinal chemistry's most effective and informative single physicochemical attribute. [32] Swiss ADME offers five openly accessible models -XLOGP3, WLOGP, MLOGP, SILICOS-IT, and iLOGP -to evaluate the lipophilicity property in a molecule.…”