Consise Synthesis and Potential Anti-angiogenic activity of N-1 Substituted Indolylchalcone Hybrids on Chorioallantoic Membrane (CAM) Assay: A Recent Study

Abstract

Objective: Synthesis of N-1 Substituted Indolylchalcone Hybrids and evaluation of anti-angiogenic activity using Chorioallantoic Membrane (CAM) Assay. The present study suggests that N-1 substituted Indolylchalcone hybrids of 2-acetyl benzimidazole might be promising analogs of angiogenesis inhibitors to manage the uncontrolled neovascularization occurring during malignant tumor development.

Methods:  Claisen-schmidt reaction is used for the synthesis of 30 Indolylchalcone hybrids, it involves condensation of N-1 substituted indole-3-carboxaldehyde and N1 substituted 2-acetyl- benzimidazole. The phase transfer catalyst, green catalyst such as anhydrous potassium carbonate (K₂CO₃) and PEG-400 are used in the alkylation and arylation. All synthesized indolylchalcone hybrids were evaluated for their antiangiogenic activity by in-vivo-chorioallantoic membrane (CAM) assay method.

Results: The synthesized indolylchalcone compounds are evaluated. The morphometric study was carried out as described by Melkonian et al. (2002). The Compounds with code C-2, I-1, I-2 are showing more potent effect on dose dependent assay of CAM. The compounds with code C-1, C-3, E-1 to E-3, M-1 and M-5 shows the significant activity, however, though the compounds with code B-1, B-2 ,CL-1 and A-5 were showing  antiangiogenic effect at 0.1 µM, but does not show any significant activity on dose dependent assay of CAM .

Conclusion: The synthesized Indolylchalcones as shown in graph possess very good dose dependent anti-angiogenic activities. The potency of anti-angiogenetic activity shows that methyl >Ethyl>Cl-benzyl> Benzyl>Isobutyl. 2-acetyl benzimidazole analogs have possible future scope to develop as potent angiogenesis inhibitors.