DESIGN, SYNTHESIS, AND ANTI-BREAST-CANCER ACTIVITY EVALUATION OF PYRROLO(PYRIDO)[2,3-d]PYRIMIDINE DERIVATIVES

Abstract

Ribociclib and palbociclib, two typical selective CDK4/6 inhibitors, which have been employed in clinic for the treatment of estrogen receptor positive (ER⁺) breast cancer, possess an active fragment of pyrrolo[2,3-d]pyrimidine and pyrido[2,3-d]pyrimidine, respectively. Herein, 25 novel pyrrolo(pyrido)[2,3-d]pyrimidine derivatives have been designed and synthesized based on molecular diversity. Their antiproliferative activity was evaluated against ER⁺ (T47D) and triple-negative (MDA-MB-436) breast cancer cell lines. The obtained results demonstrated that dihydroartemisinin-pyrrolo[2,3-d]pyrimidine and dihydroartemisinin-pyrido[2,3-d]pyrimidine derivatives are characterized by significant antiproliferative effects on both cell lines and have higher anticancer activity against triple-negative breast cancer cells compared to ribociclib.