Synthesis and Preclinical Evaluation of Indole Triazole Conjugates as Microtubule Targeting Agents that are Effective against MCF-7 Breast Cancer Cell Lines

CDATA[Background: Microtubules are considered to be an important therapeutic target for most of the anticancer drugs. These are highly dynamic structures comprising of α-tubulin and β-tubulin which are usually heterodimers and found to be involved in cell movement, intracellular trafficking, and mitosis inhibition of which might kill the tumour cells or inhibit the abnormal proliferation of cells. Most of the tubulin polymerization inhibitors, such as Vinca alkaloids, consist of Indole as the main scaffold. The literature also suggests using triazole moiety in the chemical entities, potentiating the inhibitory activity against cell proliferation. So, in our study, we used indole triazole scaffolds to synthesize the derivatives against tubulin polymerization. OBJECTIVE: The main objective of this study to synthesize indole triazole conjugates by using environmentally friendly solvents (green chemistry) and click chemistry. To carry out the MTT assay and tubulin polymerization assay for the synthesized indole triazole conjugates. METHODS: All the synthesized molecules were subjected to molecular docking studies using Schrodinger suite and the structural confirmation was performed by Mass, proton-NMR and carbon-NMR, documented in DMSO and CDCL3. Biological studies were performed using DU145 (prostate cancer), A-549 (lung cancer) and, MCF-7 (breast cancer), cell lines obtained from ATCC were maintained as a continuous culture. MTT assay was performed for the analogues using standard protocol. Cell cycle analysis was carried out using flow cytometry. RESULTS: value of 2.51μM. CONCLUSION: Indole triazole hybrids were synthesized using click chemistry, and docking studies were carried out using Schrodinger for the designed molecules. Process Optimization has been done for both the schemes. Twelve compounds (2a-2l) have been successfully synthesized and analytical evaluation was performed using NMR and HR-MS. In vitro evaluation was for the synthesized molecules to check tubulin polymerization inhibition for antiproliferative action. Among the synthesized compounds, 2c and 2g have potent anticancer activities by inhibiting tubulin polymerization.