In Silico Screening of Synthetic and Natural Compounds to Inhibit the Binding Capacity of Heavy Metal Compounds against EGFR Protein of Lung Cancer.

Abstract

Inorganic pollutant, specifically heavy metals' contamination, is a significant matter of concern and is one of the key contributors in various health disorders including cancer. However, the interaction of heavy metals (HMs) with lung cancer has rarely been explored yet. Therefore, the present study was intended with the aim to identify the interactions of HMs with the target protein “epidermal growth factor receptor (EGFR)” of lung cancer and explore potential drug candidates, which could inhibit the active site of EGFR against HM exposure. The molecular operating environment (MOE) tool was used to study the interactions of HMs with EGFR protein. The drug-drug interaction (DDI) network approach was used to identify the potential drug candidates, which were further confirmed and compared with the commercial medicines/control group. Various compounds of twenty-three HMs were docked with EGFR protein. Out of which tinidazole, thallium bromodimethyl, and silver acetate (Sn, Ti, and Ag compounds) showed strong interactions with EGFR based on lowest-scoring values (-20.42, -7.86, and -7.74 kcal/mol, respectively). Among 1280 collected drug candidates, three synthetic compounds viz., ZINC00602803, ZINC00602685, and ZINC06718468 and three natural compounds (berberine chloride, transresveratrol, and ellagic acid) depicted strong binding capacity with EGFR. Specifically, the scoring value of ZINC00602803 (-30.99 kcal/mol) was even lowest than standard lung cancer drugs (afatinib, erlotinib, and gefitinib). Our findings revealed that both natural and synthetic compounds having strong associations with EGFR protein could be potential candidates to inhibit the interaction between HMs and lung cancer protein and can also be used as an alternative for the prevention and treatment of lung cancer. However, in vitro and in vivo studies should be conducted to validate the aforementioned natural and synthetic compounds.