Synthesis, biological evaluation and molecular docking studies of novel pyrrolo[2,3-d]pyrimidin-2-amine derivatives as EGFR inhibitors

In the present investigation, we employed pyrrolo[2,3-d] pyrimidine, potassium amide, and liquid ammo-nia to synthesize pyrrolo[2,3-d]pyrimidin-2-amine derivatives (4a-n). Spectroscopic techniques and ele-mental analyses were used to determine the structure of the title compounds. For their in vitro cytotoxic activity against the human cancer cell lines MCF-7 (breast), HCT116 (colorectal), and HepG2 (liver), all the synthesized compounds were evaluated. These compounds 4a-n were exhibiting moderate to significant cytotoxic effects against all of the cancer cell lines evaluated. Further, the inhibitory effects of potent compounds (4d, 4e, 4f, 4h, 4i, and 4m) on epidermal growth factor receptor tyrosine kinase (EGFR-TK) were examined. Three compounds, 4d, 4f, and 4h, exhibited good inhibitory effects with IC50 values of 0.107, 0.159, and 0.196 mu M, respectively. When potent compounds (4d, 4f, and 4h) were docked into the EGFR-TK protein's active region, it became clear that this protein would be an excellent target for the creation of novel anticancer drugs. All the compounds are compiled with Lipinski's rule of five, which suggests promise for development as oral drug candidates.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, pyrrolo[2,3-d]pyrimidine-2-amine derivatives (4a-n) were synthesized using pyrrolo[2,3-d]pyrimidine, potassium amide, and liquid ammonia. The structure of these compounds was determined using spectroscopic techniques and elemental analyses. The synthesized compounds were evaluated for their cytotoxic activity against human cancer cell lines, and moderate to significant cytotoxic effects were observed. Further investigation revealed that some compounds displayed inhibitory effects on epidermal growth factor receptor tyrosine kinase (EGFR-TK), making it a potential target for novel anticancer drug development. All compounds complied with Lipinski's rule of five, indicating their potential as oral drug candidates.