Kalın, Şeyda Nur; Bayındırlı, Kübra Nur; Toraman, Emine; Günaydın, Şükran; Keleş, Fatmanur; Altay, Ahmet; Budak, Harun

Lichen secondary metabolites with many remarkable biological activities are used in cancer treatments due to their low side effects and high anticancer potential. In particular, these metabolites constitute an interesting research area in cancer treatments due to their potential to induce apoptosis and suppress metastasis by inhibiting cancer-related signaling pathways. The Wnt/β-catenin signaling pathway plays a role in important biological processes such as oncogenesis, cell cycle regulation, cell proliferation, metastasis, differentiation, apoptosis, and drug resistance. Therefore, inhibition of this pathway is a potential target in cancer therapies. There is no detailed study explaining the potential anticancer molecular mechanism of the lichen secondary metabolite lobaric acid (LA) on breast cancer. Here, it is aimed to investigate the effect of LA on viability, apoptosis, and migration in MCF-7 cells and to elucidate the relationship between the potential anticancer effect and the Wnt/β-catenin signaling pathway. The dose- and time-dependent viability of LA-treated MCF-7 cells was evaluated by XTT assay, and the IC50 value was determined as 44.21 μg/mL at 48 h. LA increased the apoptotic cell population, as shown by flow cytometry analysis, qPCR, and Western blot results. LA inhibited β-catenin by inducing GSK3-β protein expression, thereby suppressing Wnt/β-catenin target genes. LA might be a natural active compound candidate for breast cancer treatment.

Lolak, Nebih; Akocak, Suleyman; Topal, Meryem; Koçyiğit, Ümit Muhammet; Işık, Mesut; Türkeş, Cüneyt; Topal, Fevzi; Durgun, Mustafa; Beydemir, Şükrü

The research and design of new inhibitors for the treatment of diseases such as Alzheimer's disease and glaucoma through inhibition of cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and carbonic anhydrase enzymes are among the important targets. Here, a series of novel sulfonamide-bearing pyrazolone derivatives (1a–f and 2a–f) were successfully synthesized and characterized by using spectroscopic and analytical methods. The inhibitory activities of these newly synthesized compounds were evaluated both in vitro and in silico for their effect on carbonic anhydrases (hCA I and hCA II isoenzymes) and ChEs. The in vitro studies showed that these novel compounds demonstrated potential inhibitory activity, with KI values covering the following ranges: 18.03 ± 2.86–75.54 ± 4.91 nM for hCA I, 24.84 ± 1.57–85.42 ± 6.60 nM for hCA II, 7.45 ± 0.98–16.04 ± 1.60 nM for AChE, and 34.78 ± 5.88–135.70 ± 17.39 nM for BChE. Additionally, many of these compounds showed promising inhibitory activity, and some showed higher potency than reference compounds. While the in silico studies have also identified the potential binding positions of these compounds, using the crystal structures of hCA I, II, AChE and BChE receptors. The varying affinities demonstrated by these designed compounds for ChEs and hCA isoenzymes show that these compounds could hold promise as potential alternative agents for selectively inhibiting ChEs and hCAs in the treatment of diseases such as Alzheimer's disease and glaucoma.