New Aminoacetylenic 2-methylindoline
Anticipated as Angiogenesis Inhibitor
in Cancer Treatment
Abdulla Nabil Al-Salihi
University of Petra, 2014
Prof. Zuhair Muhi-eldeen Prof. Tawfiq Arafat
One of the most recent approach in cancer treatment is the angiogenesis inhibitors. This
is represented by endothelial growth factor receptor inhibitors and vascular endothelial
growth factor receptor inhibitors such as Thalidomide and Lenalidomide.
We invision structural analogues to lenalidomide namely aminoacetylenic-2-
methylindoline series as novel and new angiogenesis inhibitors.
Aminoacetylenic 2-mthylindoline derivatives were synthesized from the reaction of 2-
methylindoline with 3-bromoprop-1-yne to generate 2-methyl-1-(prop-2-yn-1-yl)-2,3-
dihydro-1H-indole (AZ-1). A mixture of 2-methyl-1-(prop-2-yn-1-yl)-2,3-dihydro-1Hindole,
paraformaldehyde, cyclic amine and cuprous chloride catalytic amount, in
peroxide free dioxane through Mannich reaction yielded the desired Aminoacetylenic 2-
methylindoline derivatives AZ2, AZ3, AZ4, AZ5, AZ6, AZ7.
The IR, DSC, 1H-NMR, 13C-NMR and elemental analysis results were consistent with the
assigned structures. The docking results showed that all the designed compounds have
good EGF (epidermal growth factor) receptor inhibition specifically AZ4 which scores -
8.3 (Kcal/mol), Additional COX II receptor inhibition specifically showed by AZ5 which
scores -8.6 (Kcal/mol) this indicate a promising effect in inhibiting the formation of new
blood vessels, thereby stop tumor metastasis, diabetic retinopathy and rheumatoid