A novel series of 12 pyrazolo[3,4-d]pyrimidine derivatives were created and evaluated in vitro for their antiproliferative activity against the NCI 60 human tumor cell line panel.

Aim: Design and synthesis of novel morpholinopyrimidine-5-carbonitriles as antitumor agents. Materials & methods: New series of morpholinopyrimidine-5-carbonitriles have been synthesized. 19 deriva... Graphical abstract

A series of pyrimidine-5-carbonitriles was designed and synthesized as potential anti-cancer agents with dual EGFR ^WT /COX-2 inhibition. Compounds 4e and 4f disclosed the highest activity on all NCI60 cell lines.

The VEGFR-2/AKT pathway is a crucial axis in tumor survival where it is highly dysregulated in many cancer types. In this research, novel coumarin-acid hydrazides were synthesized and assayed for their anticancer activity in MCF-7 and Panc-1 cells via MTT assay where most compounds especially 4f and 4k showed promising antiproliferative activity with an IC₅₀ of 0.73, 1.19 and 0.84, 3.61 μM against both cell lines, respectively. Their inhibitory activity on VEGFR-2/AKT-1 proteins was very promising with IC₅₀ values of 0.18 and 0.12 μM on VEGFR-2 and 5.7 and 8.1 μM on AKT by 4f and 4k, respectively. Also, flow cytometry revealed cell cycle arrest with elevated caspase 8 and 9 levels leading to apoptosis by both compounds. Furthermore, docking studies revealed binding patterns similar to the reference ligands in VEGFR-2 and AKT-1 binding sites. Thus, these novel coumarin derivatives are promising anticancer leads via inhibiting the VEGFR-2/AKT axis and apoptosis induction.