77295-62-6Relevant articles and documents
Anti-inflammatory, ulcerogenic and platelet activation evaluation of novel 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids
Felipe, Josyelen L.,Cassamale, Tatiana B.,Louren?o, Leticia D.,Carvalho, Diego B.,das Neves, Amarith R.,Duarte, Rita C.F.,Carvalho, Maria G.,Toffoli-Kadri, Monica C.,Baroni, Adriano C.M.
, (2021/12/27)
This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs 8–13 (L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non– ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski's rule of five. A molecular docking study showed that the hybrids 8–13 (L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.
Synthesis and biological evaluation of 1-(benzofuran-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole derivatives as tubulin polymerization inhibitors
Qi, Zhi-Yuan,Hao, Shu-Yi,Tian, Heng-Zhi,Bian, Hong-Li,Hui, Ling,Chen, Shi-Wu
, (2019/11/13)
The key functions of microtubules and the mitotic spindle in cell division make them attractive targets for cancer therapy. In this study, a series of 1-(benzofuran-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole derivatives was synthesized, and their
Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G
Trefzger, Ozildéia S.,das Neves, Amarith R.,Barbosa, Natália V.,Carvalho, Diego B.,Pereira, Indiara C.,Perdomo, Renata T.,Matos, Maria F. C.,Yoshida, Nidia C.,Kato, Massuo J.,de Albuquerque, Sérgio,Arruda, Carla C. P.,Baroni, Adriano C. M.
, p. 313 - 324 (2018/11/30)
Using bioisosterism as a medicinal chemistry tool, 16 3,5-diaryl-isoxazole analogues of the tetrahydrofuran neolignans veraguensin, grandisin and machilin G were synthesized via 1,3-dipolar cycloaddition reactions, with yields from 43% to 90%. Antitrypanosomatid activities were evaluated against Trypanosoma cruzi, Leishmania (L.) amazonensis and Leishmania (V.) braziliensis. All compounds were selective for the Leishmania genus and inactive against T.?cruzi. Isoxazole analogues showed a standard activity on both promastigotes of L.?amazonensis and L.?braziliensis. The most active compounds were 15, 16 and 19 with IC50 values of 2.0, 3.3 and 9.5?μM against L.?amazonensis and IC50 values of 1.2, 2.1 and 6.4?μM on L.?braziliensis, respectively. All compounds were noncytotoxic, showing lower cytotoxicity (>250?μM) than pentamidine (78.9?μM). Regarding the structure–activity relationship (SAR), the methylenedioxy group was essential to antileishmanial activity against promastigotes. Replacement of the tetrahydrofuran nucleus by an isoxazole core improved the antileishmanial activity.
