Design, biological evaluation, molecular docking study and in silico ADME prediction of novel imidazo[2,1-b]thiazole derivatives as a novel class of α-glucosidase inhibitors

Inhibiting the degradation of carbohydrates into glucose is considered to be an effective treatment for type 2 diabetes mellitus. Herein, a series of novel thiosemicarbazide and 1,2,4-triazole-3-thione derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their α-glucosidase inhibitory activity. Compound5c(IC50: 4.54 ± 0.19 µM) was found approximately 47 times more active thanAcarbose(IC50: 214.71 ± 8.34 µM). In addition to thein vitroanalysis, molecular docking studies were employed to explore the possible binding interactions of the title compounds. Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship between biological, electronic, and physicochemical qualifications of the target compounds was determined. Consequently, our studies indicated that these imidazo[2,1-b]thiazole derivatives possess the potential of being a novel class of α-glucosidase inhibitors

Identification of AKT1/β-catenin mutations conferring cetuximab and chemotherapeutic drug resistance in colorectal cancer treatment

In anticancer therapy, the effectiveness of therapeutics is limited by mutations causing drug resistance.KRASmutations 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 betweenAKT1/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 ofAKT1E17K, E49K, and L52R mutations, as well asCTNNB1T41A, S45F, and S33P mutations compared with that of respective WT proteins.AKT1/CTNNB1mutations 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/CTNNB1mutations may be used as an important predictive biomarker in CRC treatment

In vitro inhibitory potential of Amaranthus lividus L. against therapeutic target enzymes

Background and Aims: The search for new enzyme inhibitors in plants is attractive because they can be used as drugs in the treatment of various diseases. Amaranthus spp. (Amaranthaceae) includes about 70 different species, some of which are edible and some of which are used in traditional medicine to treat various ailments. Amaranthus lividus L. is a vegetable whose stems and leaves are used for human consumption in Turkey