85103-41-9Relevant articles and documents
Efficient Synthesis of Fluorinated [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles
Dhotre, B. K.,Jagrut, V. B.,Pathan, M. A.,Patharia, M. A.,Raut, S. V.
, p. 1135 - 1140 (2021/09/08)
Abstract: An efficient synthesis of fluorinated [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives has been achievedby cyclocondensation of 5-substituted 4-amino-1,2,4-triazole-3-thiols withfluoro-substituted aromatic acids using phosphoryl chloride as a cyclizingagent. The synthesized compounds were characterized by spectroscopic techniques,including IR, 1H NMR, and mass spectra.
1,2,4-Triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds: A potent ameliorant of carrageenan-induced inflammation by lessening proinflammatory mediators
Pathak, Prateek,Shukla, Parjanya K.,Naumovich, Vladislav,Grishina, Maria,Verma, Amita,Potemkin, Vladimir
, (2019/11/16)
Inflammation acts as an alarming signal for the progression of various biological complications. Various reports in the literature have revealed that heterocycle-containing synthetic compounds have a restorative capability against acute and chronic inflammatory stages. In the current study, we synthesized a series of 1,2,4-triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds and evaluated their impacts against carrageenan-induced paw edema and proinflammatory markers in Wistar rats. Further, 3D QSAR study (three-dimensional quantitative structure–activity relationships), ADMET (absorption, distribution, metabolism, and excretion) profiling, and docking studies were performed to determine the possible mechanism of the action of the derivatives. The study shows that the most active derivatives, 13f and 13g, have optimal logP, a higher anti-inflammatory activity score, and poor metabolism at various sites of cytochrome P450. The docking studies recommended that the synthesized compounds have a similar affinity as the ligands A307, 63X, and S58 to interact with tumor necrosis factor-α, COX-1, and COX-2. So, these molecules will definitely hold a promise for the future drug development initiative.
Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
, (2020/10/08)
Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
