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

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 (, , and ) were selected by the National Cancer Institute (NCI) to evaluate their antiproliferative activity against a panel of 60 human tumor cell lines. 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 at different concentrations against these two cells, implying that exerted notable cytotoxicity toward HCT-116 (IC = 5.11 ± 2.14 μM) and MCF-7 (IC = 6.06 ± 3.09 μM) cells in comparison with cisplatin (IC = 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 bound to DNA, forming hydrogen bonding through the quinone scaffold. pharmacokinetic determinants indicated that demonstrated drug-likeness with a remarkable pharmacokinetic profile for future mechanistic anti-CRC and anti-breast cancer activity studies.