Design, Synthesis, and Biological Evaluation of Indole-2-carboxamides as Potential Multi-Target Antiproliferative Agents.

A small set of indole-based derivatives, IV and Va - I , was designed and synthesized. Compounds Va - i demonstrated promising antiproliferative activity, with GI 50 values ranging from 26 nM to 86 nM compared to erlotinib's 33 nM. The most potent antiproliferative derivatives- Va , Ve , Vf , Vg , and Vh -were tested for EGFR inhibitory activity. Compound Va demonstrated the highest inhibitory activity against EGFR with an IC 50 value of 71 ± 06 nM, which is higher than the reference erlotinib (IC 50 = 80 ± 05 nM). Compounds Va , Ve , Vf , Vg , and Vh were further tested for BRAF V600E inhibitory activity. The tested compounds inhibited BRAF V600E with IC 50 values ranging from 77 nM to 107 nM compared to erlotinib's IC 50 value of 60 nM. The inhibitory activity of compounds Va , Ve , Vf , Vg , and Vh against VEGFR-2 was also determined. Finally, in silico docking experiments attempted to investigate the binding mode of compounds within the active sites of EGFR, BRAF V600E , and VEGFR-2.