OBJECTIVES: Based on the multitargeted biological activities approach of ligustrazine based chalcones, in current study 18 synthetic ligustrazine-containing α, β-unsaturated carbonyl-based 1, 3-Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on growth of five different types of cancer cells.
METHODS: All compounds were evaluated for anticancer effects on various cancer cell lines by propidium iodide fluorescence assay and various other assays were performed for mechanistic studies.
RESULTS: Majority of compounds exhibited strong inhibition of cancer cells especially synthetic compounds 4a and 4b bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in main structural backbone were found most powerful inhibitors of cancer cell growth. Most active 9 compounds among whole series were selected for further studies related to different cancer targets including EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E.
CONCLUSION: Synthetic derivatives including 4a-b and 5a-b showed multitarget approach and showed strong inhibitory effects on EGFR, FAK and BRAF while three compounds including 3e bearing methoxy substitution, 4a and 4b with 1- pyridin-3-yl-ethanone moiety showed the inhibition of tubulin polymerization.
MATERIAL AND METHODS: Obese-pregnant women, and women underwent BSs before the current pregnancy, with complete antenatal, and delivery records were included in the current study. Collected data were analyzed using MedCalc 20.106 to calculate the odd ratio (OR), and relative risk (RR) of adverse maternal, and fetal outcomes in relation to maternal obesity vs. BSs.
RESULTS: Data of 14,474 pregnant women were collected during this study; 33.94% (4912/14474) of them were obese, and 3.8% (546/14474) of them had previous BSs before the current pregnancy. The obese group has significantly higher odds, and RR of gestational diabetes mellitus (GDM) [OR 1.9 (p = 0.0001), and RR 1.79 (p = 0.0001)], gestational hypertension [OR 1.7 (p = 0.0002), and RR 1.6 (p = 0.0003)], and preeclampsia (PE) [OR 1.7 (p = 0.0001), and RR 1.6 (p = 0.0001)] compared to BSs group. The obese group has also significantly higher odds, and RR of cesarean sections (CSs) [OR 1.3 (p = 0.008), and RR 1.25 (p = 0.01)], and large for gestational age [OR 1.39 (p = 0.01), and RR 1.3 (p = 0.02)] compared to BSs group.
CONCLUSIONS: About 33.94% of the reproductive-age women in Kuwait are obese, and 3.8% of them had previous BSs. Obese-pregnant women are at increased risks of GDM, gestational hypertension, PE, and CSs. Bariatric surgeries reduced the rates of GDM, gestational hypertension, PE, and CSs significantly.
Methods: Three semi-synthetic series of compounds (C1-4, P1-4, and G1-4) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of Amaranthus spinosus L. (p-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.
Results: Compounds C4 and G4 showed superior inhibitory activity against EGFR (IC50: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC50: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds C4 and G4 exhibited the highest cytotoxic activity with average IC50 values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.
Discussion: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.