Analysis of Quinolinequinone Analogs with Promising Cytotoxic Activity against Breast Cancer

Abstract

In an effort to develop potent and secure antiproliferative lead compounds, five quinolinequinones (AQQ1‐5) described previously have been selected and submitted to the National Cancer Institute (NCI) of Bethesda. Four of five quinolinequinones (AQQ2‐5) were selected for five‐dose screening and they displayed promising antiproliferative effects against several cancer types. All AQQs showed a super anticancer profile with low micromolar GI50 and TGI values against most cell lines. AQQ2‐5 reduced the proliferation of all some cell lines at a single dose and five additional doses. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ3. Concomitantly, IC50 values of AQQ2 against MCF7 and T‐47D cell lines of breast cancer, DU‐145 cell line of prostate cancer, HCT‐116 cell line of colon cancer, and HaCaT human keratinocytes were determined. AQQ2 exhibited anticancer activity through the induction of apoptosis and caused alterations in the cell cycle. In silico pharmacokinetic studies of all analogs have been carried out against ATR, CHK1, WEE1, CDK1, and CDK2. In addition to this, in vitro ADME and in vivo pharmacokinetic profiling for the most effective AAQ (AAQ2).

Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile

“…Complementing these findings with scratch assay results (which provide insights into the potential anti-metastatic properties of AQQ1 by assessing its impact on cancer cell migration and invasion) we observed that DU-145 cell migration was inhibited by 13.37% ± 7.07 with 1 μM AQQ1 , by 23.68% ± 7.39 with 2.5 μM AQQ1 , and by 49.77% ± 8.45 with 5 μM AQQ1 ( Figure 4 B). Furthermore, both our recent studies and those conducted by other research groups have reported on the cytotoxic and antiproliferative activities of various quinoline derivatives [ 12 , 30 ].…”

“…These findings have made it a research topic for many scientists to obtain new biologically active synthetic molecules with a quinolinequinone moiety, which have a high tendency to undergo redox reactions. Scientific studies conducted by our group in this direction support that molecules with this moiety are building blocks that can be effective in both antimicrobial and cancer studies [ 11 , 12 , 13 ]. In light of the encouraging discoveries that have been made by our group, we engaged in comprehensive investigations aimed at identifying novel lead molecules for the treatment of cancer.…”