Synthesis and Biological Evaluation of Novel N-Substituted 3-Methylindole Derivatives
ABSTRACT
Objective:
Ten novel compounds with the general structure of 1-[(substituted-1-piperidinyl)methyl)]-3-methyl-1H-indole and 1-[(4-(substituted-1-piperazinyl)methyl)]-3-methyl-1H-indole, were synthesized using one-pot reaction method and investigated for their cytotoxic activity against MCF-7 and noncancerous human umbilical vein endothelial cells (HUVECs).
Materials and Methods:
The synthesis of the target compounds was carried out using a one-pot reaction method, in a typical procedure, 3-methylindole (2.2 mmol, 300 mg) was dissolved in 20 mL of ethanol in a round bottom flask, then formaldehyde 37% (3 mmol) and substituted piperidine or piperazine derivatives (2.2 mmol) were added. The reaction mixture was then refluxed for 4–6 hours.
Results:
In vitro cytotoxic activity screening of the compounds was performed against breast cancer (MCF-7) and noncancerous HUVEC lines. Compounds 1, 2, 3, 9 and 10 exhibited selective inhibitory effect on MCF-7 cells with IC50 values of 27, 53, 35, 32 and 31 μM respectively.
Conclusion:
The anticancer activity of the target compounds was examined against breast cancer cell line MCF-7 and noncancerous HUVEC cell line using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay to investigate their selective cytotoxicity effect, tamoxifen was used as reference drug. Compounds 1, 2, 3, 9 and 10 exhibited moderate cytotoxic activity comparing to the standard and showed a selective inhibitory effect on MCF-7 cells with selectivity index (SI) values of 3.21, 1.08, 2.90, 1.48 and 2.29 respectively. The IC50 values of these compounds on MCF-7 cell line were determined as follows: 27, 53, 35, 32 and 31 μM. These compounds’ IC50 values on HUVECs were obtained as 85, 57, 100, 48 and 71 μM.
Keywords:
Indole,
piperidine,
piperazine,
3-Methyl Indole,
anticancer.
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