73568-26-0Relevant articles and documents
Synthesis and characterization of biologically important quinoline incorporated triazole derivatives
D'Souza, Vineetha Telma,Nayak, Janardhana,D'Mello, Desmond Edward,Dayananda
, (2020/11/04)
Triazoles are well recognized in literature for their significant biologically active heterocyclic compounds. Also the quinoline nucleus found in several natural products shows a varied biological activity. Keeping in the view of these observations, a novel series of 6/7/8-substtuted-2-[(5-((4-chlorophenoxy)methyl)-4H-1,2,4-triazol-3-yl)thio]quinoline-3-carbaldehydes and 6/7/8-substituted-2-[(5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio]quinoline-carbaldehydes were synthesized by the condensation of 5-(4-chloro phenoxy methyl)-2,4-dihydro-1,2,4-triazole-3-thiones and 5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiols with 6/7/8-substituted-2-chloro quinoline-3-carbaldehydes. The new series were established by Mass, NMR and IR spectroscopy and were also screened for their antimicrobial activities. A few of the novel compounds exhibited tremendous bioactivities compared to that of normal drug.
Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
Ibrahim, Tarek S.,Hawwas, Mohamed M.,Malebari, Azizah M.,Taher, Ehab S.,Omar, Abdelsattar M.,Neamatallah, Thikryat,Abdel-Samii, Zakaria K.,Safo, Martin K.,Elshaier, Yaseen A. M. M.
, p. 802 - 818 (2021/03/29)
A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC50 ranging from 0.010 to 0.042 μM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G2/M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer.Highlights A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised. Compound 12c showed significant antiproliferative activities against different cancer cell lines. Compound 12c effectively inhibited tubulin polymerisation and competed with [3H] colchicine in binding to tubulin. Compound 12c arrested the cell cycle at G2/M phase, effectively inducing apoptosis and inhibition of cell migration.
Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition
Ghanim, Amany M.,Rezq, Samar,Ibrahim, Tarek S.,Romero, Damian G.,Kothayer, Hend
, (2021/04/23)
Based on the observed pharmacophoric structural features for the reported dual COX/15-LOX inhibitors and inspired by the abundance of COX/LOX inhibitory activities reported for the 1,2,4-triazine and quinoline scaffolds, we designed and synthesized novel 1,2,4-triazine-quinoline hybrids (8a-n). The synthesized hybrids were evaluated in vitro as dual COXs/15-LOX inhibitors. The new triazine-quinoline hybrids (8a-n) exhibited potent COX-2 inhibitory profiles (IC50 = 0.047–0.32 μM, SI ～ 20.6–265.9) compared to celecoxib (IC50 = 0.045 μM, SI ～ 326). Moreover, they revealed potent inhibitory activities against 15-LOX enzyme compared to reference quercetin (IC50 = 1.81–3.60 vs. 3.34 μM). Hybrid 8e was the most potent and selective dual COX-2/15-LOX inhibitor (COX-2 IC50 = 0.047 μM, SI = 265.9, 15-LOX IC50 = 1.81 μM). These hybrids were further challenged by their ability to inhibit NO, ROS, TNF-α, IL-6 inflammatory mediators, and 15-LOX product, 15-HETE, production in LPS-activated RAW 264.7 macrophages cells. Compound 8e was the most potent hybrid in reducing ROS and 15-HETE levels showing IC50 values of 1.02 μM (11-fold more potent than that of celecoxib, IC50 = 11.75 μM) and 0.17 μM (about 43 times more potent than celecoxib, IC50 = 7.46 μM), respectively. Hybrid 8h exhibited an outstanding TNF-α inhibition with IC50 value of 0.40 μM which was about 25 times more potent than that of celecoxib and diclofenac (IC50 = 10.69 and 10.27 μM, respectively). Docking study of the synthesized hybrids into the active sites of COX-2 and 15-LOX enzymes ensures their favored binding affinity. To our knowledge, herein we reported the first 1,2,4-triazine-quinoline hybrids as dual COX/15-LOX inhibitors.
