Synthesis, crystallographic characterization, molecular docking and biological activity of isoquinoline derivatives
CHEMISTRY CENTRAL JOURNAL
Authors: Abuelizz, Hatem A.; Al-Salahi, Rashad; Al-Asri, Jamil; Mortier, Jeremie; Marzouk, Mohamed; Ezzeldin, Essam; Ali, Azza A.; Khalil, Mona G.; Wolber, Gerhard; Ghabbour, Hazem A.; Almehizia, Abdulrahman A.; Jaleel, Gehad A. Abdel
Abstract
The main objective of this work was to synthesize novel compounds with a benzo[de][1,2,4] triazolo[5,1-a] isoquinoline scaffold by employing ( dioxo-benzo[de] isoquinolin-2-yl) thiourea as a building block. Molecular docking was conducted in the COX-2 active site to predict the plausible binding mode and rationalize the structure-activity relationship of the synthesized compounds. The structures of the synthesized compounds were confirmed by HREI-MS, and NMR spectra along with X-ray diffraction were collected for products 1 and 5. Thereafter, anti-inflammatory effect of molecules 1-20 was evaluated in vivo using carrageenan-induced paw edema method, revealing significant inhibition potency in albino rats with an activity comparable to that of the standard drugs indomethacin. Compounds 8, 9, 15 and 16 showed the highest anti-inflammatory activity. However, thermal sensitivity-hot plat test, a radiological examination and motor coordination assessment were performed to test the activity against rheumatoid arthritis. The obtained results indicate promising anti-arthritic activity for compounds 9 and 15 as significant reduction of the serum level of interleukin-1 beta [IL-1 beta], cyclooxygenase-2 [COX-2] and prostaglandin E2 [PGE2] was observed in CFA rats.
CeRNA Expression Profiling Identifies KIT-Related circRNA-miRNA-mRNA Networks in Gastrointestinal Stromal Tumour
FRONTIERS IN GENETICS
Authors: Jia, Ning; Tong, Hanxing; Zhang, Yong; Katayama, Hiroshi; Wang, Yuan; Lu, Weiqi; Zhang, Sumei; Wang, Jin
Abstract
Gastrointestinal stromal tumours (GISTs) are the most common human sarcomas and are typically located in the stomach or small intestine. Although circular RNAs (circRNAs) reportedly play vital roles in tumour oncogenesis and progression, the molecular basis of the aggressive tumour biology of these circRNAs in GISTs remains unclear. In this study, we applied SBC ceRNA microarrays to screen for tumour-specific circRNA profiles in GISTs and identified that a total of 5,770 circRNAs and 1,815 mRNAs were differentially expressed in GISTs. Three significantly differential circRNAs (circ_0069765, circ_0084097, and circ_0079471) and their host genes (KIT, PLAT, and ETV1) were also verified in 68 pairs of GISTs and adjacent normal gastrointestinal tissues by qRT-PCR. A GIST-specific circRNA-miRNA-mRNA regulatory network analysis demonstrated that the specific KIT-related regulatory networks involved the three circRNAs, the circRNA host genes and three miRNAs (miR-142-5p, miR-144-3p and miR-485-3p), which may be key regulators of GISTs that could serve as molecular biomarkers and potential therapeutic targets for this malignant disease.