In Vitro Cytotoxicity Evaluation of Plastoquinone Analogues against Colorectal and Breast Cancers along with In Silico Insights

Abstract

Colorectal cancer (CRC) and breast cancer are leading causes of death globally, due to significant challenges in detection and management. The late-stage diagnosis and treatment failures require the discovery of potential anticancer agents to achieve a satisfactory therapeutic effect. We have previously reported a series of plastoquinone analogues to understand their cytotoxic profile. Among these derivatives, three of them (AQ-11, AQ-12, and AQ-15) were selected by the National Cancer Institute (NCI) to evaluate their in vitro antiproliferative activity against a panel of 60 human tumor cell lines. AQ-12 exhibited significant antiproliferative activity against HCT-116 CRC and MCF-7 breast cancer cells at a single dose and further five doses. MTT assay was also performed for AQ-12 at different concentrations against these two cells, implying that AQ-12 exerted notable cytotoxicity toward HCT-116 (IC50 = 5.11 ± 2.14 μM) and MCF-7 (IC50 = 6.06 ± 3.09 μM) cells in comparison with cisplatin (IC50 = 23.68 ± 6.81 μM and 19.67 ± 5.94 μM, respectively). This compound also augmented apoptosis in HCT-116 (62.30%) and MCF-7 (64.60%) cells comparable to cisplatin (67.30% and 78.80%, respectively). Molecular docking studies showed that AQ-12 bound to DNA, forming hydrogen bonding through the quinone scaffold. In silico pharmacokinetic determinants indicated that AQ-12 demonstrated drug-likeness with a remarkable pharmacokinetic profile for future mechanistic anti-CRC and anti-breast cancer activity studies.

Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling

“…Encouraged by these results, our study was conducted with non‐halogenated PQ analogs as a model substrate for treating colorectal cancer by performing in vitro and in silico studies (Ciftci, Sever, Ocak, et al, 2022). We also showed strong action toward the two cell lines (HCT‐116 and MCF7) with enhanced apoptosis in both cell lines (Ciftci, Sever, Bayrak, et al, 2022). Our research group followed the 1,4‐quinone moiety as a main part condensed with pyridine, named quinolinequinones, for cancer research, including its potential in the drug discovery field, and, last but not least, its potential impact in the field of monitoring response and toxicity to different cancer cell lines.…”

A Fluorescent Probe for Protein Misfolding and Aggregation Due to Oxidative Stress Based on a 7-Azaindole-BODIPY Derivative

“…16 A concentration of 10 μM was chosen for cisplatin within the order of magnitude of IC50 values reported for MCF-7 cells in previous works. [19][20][21][22][23] After incubation, the cells were washed five times with PBS. After the treatment, FLIM images of the cells were acquired using a MicroTime 200 microscope (PicoQuant).…”

Novel N -Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations

“…The newly synthesised analogues were sent to the National Cancer Institute, Germantown, MD, USA for testing their potential anti-cancer activity after 48 h using sulforhodamine B assay 68 . Parameters for cellular growth inhibition including 50% growth inhibitory concentration (GI 50 ) were determined in 60 different cancer cell lines represent nine human cancers: breast, central nervous system, colon, kidney, leukaemia, lung, melanoma, ovary, and prostate 69 deposited in National Cancer Institute, USA as presented in Tables 1 and 2 . The one-dose results resemble the mean graphs from the 5-dose experiment in appearance and presented as a mean graph of the treated cells’ growth percentage.…”