In anticancer therapy, the effectiveness of therapeutics is limited by mutations causing drug resistance. KRAS mutations are the only determinant for cetuximab resistance in patients with colorectal cancer (CRC). However, cetuximab treatment has not been fully successful in the majority of patients with wild‑type (WT) KRAS. Therefore, it is important to determine new predictive mutations in CRC treatment. In the present study, the association between AKT1/β-catenin (CTNNB1) mutations with the drug resistance to cetuximab and other chemotherapeutics used in the CRC treatment was investigated by using site‑directed mutagenesis, transfection, western blotting and cell proliferation inhibition assay. Cetuximab resistance was higher in the presence of AKT1 E17K, E49K and L52R mutations, as well as CTNNB1 T41A, S45F and S33P mutations compared with that of respective WT proteins. AKT1/CTNNB1 mutations were also associated with oxaliplatin, irinotecan, SN‑38 and 5‑fluorouracil resistance. Furthermore, mutant cell viability in oxaliplatin treatment was more effectively inhibited compared with that of the other chemotherapeutic drugs. In conclusion, AKT1/CTNNB1 mutations may be used as an important predictive biomarker in CRC treatment.

Ancient physicians frequently used the resin of Ferula species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of Ferula species. The dichloromethane extract of the roots of Ferula huber-morathii exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC₅₀ = 52 µg/mL, 72 µg/mL, and 20 µg/mL, respectively). Fifteen sesquiterpene coumarin ethers with cytotoxic activity were isolated from the dichloromethane extract of the roots of F. huber-morathii using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (1), conferol (2), feselol (3), badrakemone (4), mogoltadone (5), farnesiferol A (6), farnesiferol A acetate (7), gummosin (8), ferukrin (9), ferukrin acetate (10), deacetylkellerin (11), kellerin (12), samarcandone (13), samarcandin (14), and samarcandin acetate (15). The absolute configuration of samarcandin (14) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (R)-MTPA ester of samarcandin (24). Conferol (2) and mogoltadone (5) were found to be the most potent cytotoxic compounds against all three cancer cell lines; furthermore, these compounds exhibit low cytotoxic activity against the non-cancerous human umbilical vein epithelial cells (HUVEC) cell line. Investigation of the biological activity mechanisms of mogoltadone (5) revealed that while suppressing the levels of Bcl-XL and procaspase-3 in the COLO 205 cancer cell line, it did not have a significant effect on the Bcl-XL, caspase-3, and β-catenin protein levels of the HUVEC cell line, which may explain the cytotoxic selectivity of mogoltadone (5) on cancer cell lines.

In search of selective cytotoxic compounds from Ferula species as potential leads for the treatment of various cancer diseases, a bioactivity-guided isolation study was performed on the roots of Ferula caspica M. Bieb. COLO 205 (colon), K-562 (leukemia), and MCF-7 (breast) cancer cell lines were used to monitor the cytotoxic activity of column fractions and determine the IC₅₀ value of the active compounds. In addition to the seven known (5–11) compounds, four previously unknown compounds: kayserin A (1), kayserin B (2), 8′-epi-kayserin B angelate (3), and 3-epi-ferulin D (4) were isolated from the dichloromethane extract of the roots of F. caspica. Structure elucidation of the isolated compounds was carried out by extensive spectroscopic analyses such as 1D- and 2D-NMR spectroscopy, High-Resolution Mass Spectroscopy (HRMS), IR spectroscopy, and UV spectroscopy. Although all of the isolated compounds showed various degrees of cytotoxic activity on COLO 205, K-562, and MCF-7 cancer cell lines, the most potent compounds were identified in the following order: 1-Hydroxy-1-(1′-farnesyl)-4,6-dihydroxyacetophenone (HFDHAP, 11), 3-epi-ferulin D (3EFD, 4), and 7-desmethylferulin D (7DMFD, 6). The cytotoxic activities of all three compounds were more potent than that of the reference compound cisplatin (Cis) against all tested cancer cell lines. Still, only HFDHAP (11) was more potent than the reference compound doxorubicin (Dox) against the MCF-7 cancer cell line. The mechanism of action of these three compounds was investigated on the COLO 205 cell line. The results indicated that compounds 4, 6, and 11 trigger caspase-3/8/9 activation and suppress the anti-apoptotic protein, Bcl-xL. Molecular docking studies confirmed the interactions of the three cytotoxic molecules with the active site of the Bcl-xL protein.

Pine tar has long been valued for its dermatological and antimicrobial properties; however, its volatile and semi-volatile component profile remains underexplored from a sustainable bioprospecting perspective. In this study, we combined dispersive liquid–liquid microextraction (DLLME) with GC-MS to develop a rapid, green workflow for profiling pine-tar volatiles, achieving greater than or equal to 50-fold enrichment from a 100 mg sample in under 10 min. GC-MS analysis on a TRB-5MS column (90 min gradient) resolved 45 compounds (match ≥ 77 %), with sesquiterpenes accounting for 71.3 % of the total area (isolongifolene 30.3 %; isobornyl acetate 16.0 %; borneol 12.4 %; (+)-longicyclene 12.5 %). Monoterpene alcohols comprised 4.4 %, while minor oxidized derivatives contributed < 3 %. Compared to conventional hydrodistillation, DLLME reduced chlorinated solvent usage by 90 % and enhanced recovery of high-boiling terpenoids by ~ 25 %. Furthermore, the cytotoxic effect of pine tar was investigated on human umbilical vein/vascular endothelium cells (HUVEC) using 3-[4,5-dimethylthiazol-2-yl]-5[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTS) cell viability assay, revealing a low level of toxicity. The resulting chemical fingerprint high lights the biotechnological potential of sesquiterpene scaffolds such as isolongifolene for microbial production and biocatalytic transformations. It also supports enzyme-based functionalization strategies for isobornyl acetate and borneol, and opens avenues in sustainable perfumery, pharmaceutical intermediates, and biofuel applications. This semi-quantitative and eco-friendly platform offers a practical foundation for the biotechnological valorization and green production of pine-tar terpenoids. In addition, the observed low cytotoxicity of pine tar contributes to the preliminary safety assessment of this natural product on human endothelial cells.

4-Thiazolidinone derivatives bearing a 2-methyl furan ring are an important class of heterocyclic compounds with wide structural variability. These heterocyclic compounds are of increasing interest in medicinal chemistry due to their reported wide spectrum of pharmacological activities, including antioxidant and anticancer effects. In this study, a series of new 4-thiazolidinone derivative compounds bearing a furan ring system were synthesized, and their antioxidant and cytotoxic activities were investigated. Thiazolidinone compounds (2a-e, 3a-j) were synthesized by refluxing hydrazines and appropriate aldehydes or ketones with mercaptoacetic acid or 2-sulfanylpropanoic acid in toluene using Dean-Stark apparatus for 4 hours. The new compounds (2a-e) were characterized by IR, 1H NMR and 13C NMR (APT) spectral studies. The cytotoxic activities of all the compounds (2a-e, 3a-j) against lung (A549), prostate (PC-3) and endometrial (ECC-1) cancer cells, and non-cancerous Human Umbilical Vein Endothelial Cells (HUVEC), were tested in vitro using 3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium inner salt (MTS) assay. The antioxidant potentials of the compounds were evaluated by the Ferric Reducing Antioxidant Power (FRAP) and the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assays. The findings revealed that 3g demonstrated the highest DPPH. scavenging activity and ferric reducing antioxidant power. Furthermore, 3h exhibited the highest cytotoxic activity, however, 3d demonstrated selective cytotoxicity toward ECC-1 cells. In conclusion, the compounds displayed weak antioxidant properties but comparatively stronger cytotoxic effects. The selectivity of 3d suggests potential for further investigations.