The inhibitory potential of 17 flavonoids on lactate dehydrogenase A (LDHA), a key enzyme in the downstream process of aerobic glycolysis in cancer cells, is investigated. Fisetin exhibited excellent inhibitory activity (IC₅₀ = 0.066 µM). Quercetin 3‐β‐D‐glucoside, quercetin 3‐galactoside, luteolin, neoeriocitrin, and luteolin 7‐O‐β‐D‐glucoside showed good inhibitory activity (IC₅₀ = 1.397–15.730 µM). Biochanin A, baicalein, quercetin, scutellarein‐7‐glucuronide, diosmetin, baicalein 7‐O‐β‐D‐glucuronide, and apigenin 7‐apioglucoside demonstrated moderate inhibitory activity (IC₅₀ = 33.007–86.643 µM). Eriodictyol, quercetin 7‐O‐β‐D‐glucoside, apigenin 7‐O‐β‐D‐glucoside, and epicatechin were inactive. The Lineweaver–Burk plot showed that fisetin competitively inhibits NADH binding (K_i = 0.024 µM). K_i values for other compounds were calculated using the Cheng–Prusoff equation (K_i = 0.2799–2.1661 µM). The study revealed that the inhibitory effect of flavonoids varies with the number and position of OH groups and bound sugars. Molecular docking analyses indicated that flavonoids exhibited strong interactions with the NADH binding site of LDHA through hydrophobic interactions and hydrogen bonds. Molecular dynamic simulations tested the stability of the fisetin‐LDHA complex over 100 ns and showed fisetin's high binding affinity to LDHA, maintaining strong hydrogen bonds. The binding energy of fisetin with LDHA was −33.928 kcal/mol, indicating its effectiveness as an LDHA inhibitor. Consequently, flavonoids identified as strong inhibitors could be potential cancer treatment sources through LDHA inhibition.

Various studies conducted on Centaurea species indicate that the relevant plant is good source of bioactive phytochemicals. In this study, in vitro studies were used to determine bioactivity properties of methanol extract of Centaurea mersinensis - endemic species in Turkey - on extensive basis. Furthermore, the interaction of target molecules, identified for breast cancer and phytochemicals in the extract, was investigated via in silico analyses to support findings received in vitro. Scutellarin, quercimeritrin, chlorogenic acid and baicalin were primary phytochemicals in the extract. Methanol extract and scutellarin had higher cytotoxic effects against MCF-7 (IC₅₀=22.17 µg/mL, and IC₅₀=8.25 µM, respectively), compared to other breast cancer cell lines (MDA-MB-231, SKBR-3). The extract had strong antioxidant properties and inhibited target enzymes, especially α-amylase (371.69 mg AKE/g extract). The results of molecular docking indicate that main compounds of extract show high-strength bonding to the c-Kit tyrosine among target molecules identified in breast cancer, compared to other target molecules (MMP-2, MMP-9, VEGFR2 kinase, Aurora-A kinase, HER2). The tyrosinase kinase (1T46)-Scutellarin complex showed considerable stability in 150 ns simulation as per MD findings, and it was coherent with optimal docking findings. Docking findings and HOMO-LUMO analysis results corresponds with in vitro experiments. Medicinal properties of phytochemicals, which was determined to be suitable for oral use along with ADMET, were found to be within normal limits except for their polarity properties. In conclusion, in vitro and in silico studies indicated that the relevant plant yields promising results regarding its potential to develop novel and effective medicational products. Communicated by Ramaswamy H. Sarma

Being the largest genus of the Compositae family with over 169 species and 199 taxons, Centaurea L. has been used in folklore for the treatment of wide range of diseases in Turkey. The antitumor activities of the Centaurea species in different types of cancer have been identified through several bioactivity studies. However, the in vitro anticancer activity of endemic Centaurea fenzlii Reichardt. has never been evaluated and published yet. In this study, the cytotoxic effect of this plant was tested in vitro against Caco-2 (human epithelial colorectal adenocarcinoma) cells by using MTT, and ATP assays. For the positive control, the cells were treated with the chemotherapeutic drug 5-fluorouracil which has been widely used in the treatment of a range of cancers. The aerial parts of the plants were collected during the flowering period and the extracts were obtained with n-hexane, dichloromethane and methanol, respectively. The extracts were applied to Caco-2 cell lines at increasing doses. The IC₅₀ values of samples were determined and their direct cytotoxic effects were measured. The extracts displayed noteworthy cell growth and proliferation inhibitory activity. Moreover, the cytotoxic effect of crude dichloromethane extract on Caco-2 cell lines was the highest compared to other extracts. This cytotoxicity screen has provided important preliminary data promoting the selection of the plant species and their different extracts with potential antitumor properties for a therapeutic option in colon cancer.