New Indolyl‐Arylaminopropenone Conjugates: Synthesis, Cytotoxicity and Apoptotic Inducing Studies

Abstract

In view of the antiproliferative potential of indoles and aryl amino propenones, a series of indolyl tethered aryl aminopropenones have been synthesized and investigated for their anti‐proliferative activity against selected human cancer cell lines. These compounds exhibited good to moderate activity against the tested cell lines. Among them, (Z)‐1‐(1‐(4‐chlorobenzyl)‐1H‐indol‐3‐yl)‐3‐((3,4,5‐trimethoxyphenyl)amino)prop‐2‐en‐1‐one (6a) and (Z)‐1‐(1‐benzyl‐1H‐indol‐3‐yl)‐3‐((3,4,5‐trimethoxyphenyl)amino)prop‐2‐en‐1‐one (6g) exhibited promising IC50 values of 2.3 μM and 1.9 μM, respectively, against MCF‐7 (human breast cancer cell line). The morphological studies indicated that compounds showed a dose dependent decrease of viable cells in MCF‐7 cell line. The flow cytometric analysis of these potential compounds revealed that they caused cell cycle arrest at G0/G1 phase. Furthermore, Annexin‐V FITC study revealed that the potential compounds induced cell death by apoptosis. In addition, molecular docking studies of the most potential compounds provided insights about the binding interactions of the compounds with Bcl‐2 protein.

Synthesis and Characterization of Thymoquinone‐Oxime (TQ‐Ox) from Thymoquinone and Evaluation of its Cytotoxic, Genotoxic, and Apoptotic Potential in Lung Cancer Cells (A549) in vitro

“…To assess the induction of apoptosis, A549 and BEAS‐2B cells were treated with below the IC 50 concentrations of TQ−Ox (2.5–30 μM) for 24 hours. Apoptosis was evaluated utilizing the Annexin‐V/FITC and PI staining kit (eBioscience Annexin V Apoptosis Detection Kit, Thermo Scientific, USA), followed by flow cytometry analysis (BD Biosciences, FACS Canto II, USA), which simultaneously monitored Annexin V‐FITC binding and propidium iodide (PI) uptake following the manufacturer‘s protocol [22] …”

“…Apoptosis was evaluated utilizing the Annexin-V/FITC and PI staining kit (eBioscience Annexin V Apoptosis Detection Kit, Thermo Scientific, USA), followed by flow cytometry analysis (BD Biosciences, FACS Canto II, USA), which simultaneously monitored Annexin V-FITC binding and propidium iodide (PI) uptake following the manufacturer's protocol. [22] Briefly, the cells were first harvested and subjected to centrifugation for separation, followed by gentle washing with phosphate-buffered saline (PBS) to remove any residual debris. Subsequently, the cells were carefully resuspended in Annexin V Binding Buffer and subjected to staining with Annexin V FITC and propidium iodide (PI).…”

The anti‐breast cancer potential of indole/isatin hybrids

“…The 3,4,5‐trimethoxy group on the phenyl ring was critical for the activity, according to the antiproliferative SARs of indole‐aminopropenone hybrids 3 (IC 50 : 1.9–36.8 µM) against MCF‐7 cancer cells, and substitution with an electron‐withdrawing group resulted in a considerable loss of activity; substituent at N‐1 position of the indole had a significant impact on the activity, and benzyl was more favorable than methyl. [ 21 ] In comparison to doxorubicin (IC 50 : 0.8 µM), hybrids 3a,b had somewhat lower potencies (IC 50 : 1.9 and 2.3 µM) against MCF‐7 cancer cells. Mechanistically, hybrids 3a,b triggered cell‐cycle arrest in the G0/G1 phase and promoted apoptosis‐caused cell death.…”