The epidermal growth factor receptor (EGFR) was found to be overexpressed in several cancers, especially in lung cancers. Finding new effective drug against EGFR is the key to cancer treatment. In this study, the GOLD docking algorithm was used to virtually screen for novel human EGFR inhibitors from the NCI database. Thirty‐four hit compounds were tested for EGFR‐tyrosine kinase (TK) inhibition. Two potent compounds, 1‐amino‐4‐(4‐[4‐amino‐2‐sulfophenyl]anilino)‐9,10‐dioxoanthracene‐2‐sulfonic acid (NSC125910), and nogalamycin N‐oxide (NSC116555) were identified with IC50 values against EGFR‐TK comparable to gefitinib; 16.14 and 37.71 nM, respectively. However, only NSC116555 demonstrated cytotoxic effects against non–small‐cell lung cancer, A549, shown in the cell cytotoxicity assay with an IC50 of 0.19 + 0.01 µM, which was more potent than gefitinib. Furthermore, NSC116555 showed cytotoxicity against A549 via apoptosis in a dose‐dependent manner.
A series of 2,4 diamino-pyrimidines have been identified from an analysis of open access high throughput anti-malarial screening data reported by GlaxoSmithKline at the 3D7 and resistant Dd2 strains. SAR expansion has been performed using structural knowledge of the most plausible parasite target. Seventeen new analogs have been synthesized and tested against the resistant K1 strain of Plasmodium falciparum (Pf). The cytotoxicity of the compounds was assessed in Vero and A549 cells and their selectivity towards human kinases including JAK2 and EGFR were undertaken. We identified compound 5n and 5m as sub-micromolar inhibitors, with equivalent anti-malarial activity to Chloroquine (CQ). Compounds 5d and 5k, μM inhibitors of Pf, displayed improved cytotoxicity with weak inhibition of the human kinases.
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