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    Antioxidant, cytotoxicity, antimicrobial, wound healing potentials and LC-MS/MS analysis of water extract of Rhus coriaria L. (sumak) leaves
    (Elsevier, 2024) Aytar, Mehmet; Boncooglu, Rukiye Yavaser; Erdogan, Omer; Basbulbul, Gamze; Ozturk, Bintug
    The object of this study was to investigate antioxidant, anticancer, antimicrobial and wound healing activities of aqueous extract of R. coriaria L. (sumak) leaves. Antioxidant activity was carried out using 1,1- diphenyl-2picrylhydrazyl (DPPH) and 2,2-azinobis(3 ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays and the extract showed 97.0 +/- 0.74% and 95.7 +/- 1.40% radical scavenging activities, respectively. For anticancer activity, cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against MCF7 breast cancer and L929 mouse fibroblast cells, and the extract was able to inhibit proliferation of MCF7 breast cancer cells with IC 50 of 129.1 +/- 9.27 mu g/mL. Wound closure assay revealed that aqueous extract at 1 mu g/mL was able to close 79% of wound gap after 24 h with high migration rate. Antimicrobial activity depicted high inhibitory effects against C. albicans (17 mm), E. coli (16 mm), P. aeruginosa (21 mm), S. aureus (17 mm), K. pneumoniae (15 mm). Furthermore, LC-MS/MS results revealed that the leaves contain phenolic compounds and mainly rich in gallic acid (2.82 mg/kg) caffeic acid (6.84 mg/kg) and ascorbic acid (45.84 mg/kg) which may be strongly associated with the remarkable biological activities the extract.
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    Synthesis of novel triazole-urea hybrids and their antiproliferative activity against pancreatic cancer through suppression of eEF2K and induction of apoptosis
    (Elsevier, 2024) Tuere, Asli; Ozdemir, Burcu; Cece, Onur; Armagan, Guliz; Erdogan, Mumin Alper; Erdogan, Omer; Cevik, Ozge
    Pancreatic cancer is one of the deadliest cancers with its highly aggressive and metastatic character and there is a huge unmet need for new drugs treating pancreatic cancer. In the present study, a series of 1,2,4-triazole-urea conjugates have been designed and synthesized as novel candidates of antiproliferative agents against pancreatic cancer cells. Among them, compounds 33, 34, 35 and 38 possesing IC50 values between 0.231 and 0.488 mu M against PANC-1 cells demonstrated the highest anti-proliferative activity. These compounds presenting the highest antiproliferative activity were evaluated for further biological studies. The same four compounds inhibited colony formation in pancreatic cancer cells dose dependently. Western blot study on the selected compounds showed that compounds 33 and 38 significantly reduced eEF2K protein levels in cancer cells. These compounds displayed an effective eEF2K activity suppression by down-regulated levels of unphosphorylated eEF2 in PANC-1 cells. Compounds 33, 34, 35 and 38 were also demonstrated to induce apoptosis and activate caspase 3/7. In silico studies were performed to predict the druggability and ADMET/ properties of the active molecules. In summary, 1,2,4-triazole-urea conjugates developed in this study represent a novel and promising lead structure with anticancer activity against pancreatic cancer achieved through eEF2K activity suppression. Compounds being referred to are the first triazole-urea hybrid molecules found to be effective against pancreatic cancer.