Centaurea mersinensis phytochemical composition and multi-dimensional bioactivity properties supported by molecular modeling.

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.

Natural flavonoids as promising 6-phosphogluconate dehydrogenase inhibitor candidates: In silico and in vitro assessments.

The primary strategy in the fight against cancer is to screen compounds that may be effective on different types of cancer. Compounds from plants seem to be a good source. The present study investigated the inhibitory effects of some flavonoids on the 6-phosphogluconate dehydrogenase (6-PGD) enzyme. We determined that quercetin, myricetin, fisetin, morin, apigenin, and baicalein exhibited powerful inhibition effects with IC50 values between 4.08 and 21.26 µM, while luteolin, kaempferol, apiin, galangin, and baicalin showed moderate effects with IC50 values between 54.15 and 138.91 µM. Quercetin competitively inhibited the binding of NADP and 6-phosphogluconate to the 6-PGD enzyme with Ki values of 0.527 ± 0.251 and 0.374 ± 0.138 µM, respectively. We calculated Ki values using the Cheng-Prusoff equation as between 0.44 and 14.88 µM. The possible interaction details of polyphenols with the active site of 6-PGD were analyzed with docking software. In silico and in vitro studies indicated that the -OH groups on the A and C ring of flavonoids bind to the enzyme's active site via hydrogen bonding, while the -OH groups on the C ring contributed significantly to the increase in the inhibitory potentials of the molecules. Molecular dynamic simulations tested the stability of the 6-PGD-quercetin complex during 100 ns. These phytochemicals were suitable for drug use when optimized with absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria. The effects of the studied compounds on cancer cell lines of potential targets were demonstrated by network analysis. In conclusion, this study suggests that flavonoids found to be potent inhibitors could serve as leading candidates to treat many cancers via 6-PGD inhibition.