103499-27-0Relevant articles and documents
Design, semisynthesis and cytotoxic activity of novel ester derivatives of betulinic acid-1,2,4 oxadiazoles
Challa, Krishna,Bhargavi, M Vijaya,Krupadanam, G L David
, p. 1158 - 1168 (2016)
Taking into consideration of the biological activity of betulinic acid derivatives containing a oxadiazole ring, the semisynthetic betulinic acid-1,2,4-oxadiazole esters (14–25) were synthesized starting from betulinic acid (1) and 5-(bromomethyl)-3-aryl-1,2,4-oxadiazoles (2–13) and final compounds were tested for cytotoxic activity on three human cancer cell lines in vitro. All tested compounds showed good cytotoxic activity. The structures of synthesized compounds are established based on infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry.
Syntheses and biological activity of platinum(II) and palladium(II) complexes with phenyl-oxadiazole-ethylenediamine ligands
Pereira, Caroline de Souza,Enes, Karine Braga,de Almeida, Angelina Maria,de Mendon?a, Camille Carvalho,da Silva, Vania Lúcia,Gallupo Diniz, Cláudio,Couri, Mara Rubia Costa,Silva, Heveline
, p. 823 - 837 (2021)
This work describes the synthesis, characterization, cytotoxicity and antibacterial activity of three ligands derived from phenyl-oxadiazole-ethylenediamine and their platinum(II) and palladium(II) complexes. These compounds were characterized by elemental analysis, and Raman, IR, and NMR spectroscopies. We have prepared complexes with different substituents on the aromatic ring to provide influence in the antibacterial activity and cytotoxicity. The antibacterial activity was evaluated against Gram-positive bacteria Staphylococcus aureus (ATCC 25213), Staphylococcus epidermidis (ATCC 12228) and Gram-negative bacteria Escherichia coli (ATCC 11229) and Pseudomonas aeruginosa (ATCC 27853). The cytotoxicity was evaluated in two different tumor cell lines: mouse metastatic mammary adenocarcinoma (4T1), and murine colon cancer cells (CT26WT), and a non-tumor cell Baby Hamster Kidney (BHK-21). Based on the results obtained for the antibacterial and the cytotoxic activity it is possible to conclude that the presence of metal and groups NO2 and CF3 contributed to antibacterial activity with low cytotoxicity.
Development of hydroxamate-based histone deacetylase inhibitors containing 1,2,4-oxadiazole moiety core with antitumor activities
Yang, Feifei,Shan, Peipei,Zhao, Na,Ge, Di,Zhu, Kongkai,Jiang, Cheng-shi,Li, Peifeng,Zhang, Hua
, p. 15 - 21 (2019)
Histone deacetylases (HDACs) has proved to be promising target for the development of antitumor drugs. In this study, we reported the design and synthesis of a class of novel hydroxamate-based bis-substituted aromatic amide HDAC inhibitors with 1,2,4-oxadiazole core. Most newly synthesized compounds displayed excellent HDAC1 inhibitory effects and significant anti-proliferative activities. Among them, compounds 11a and 11c increased acetylation of histone H3 and H4 in dose-dependent manner. Furthermore, 11a and 11c remarkably induced apoptosis in HepG2 cancer cells. Finally, the high potency of compound 11a was rationalized by molecular docking studies.
Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles
Caneschi, Wiliam,Enes, Karine Braga,Carvalho de Mendon?a, Camille,de Souza Fernandes, Fábio,Miguel, Fabio Balbino,da Silva Martins, Jefferson,Le Hyaric, Mireille,Pinho, Roberto Rosas,Duarte, Lucas Mattos,Leal de Oliveira, Marcone Augusto,Dos Santos, Hélio F.,Paz Lopes, Miriam Teresa,Dittz, Dalton,Silva, Heveline,Costa Couri, Mara Rubia
, p. 18 - 30 (2019/01/16)
A series of1,2,4- and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their anticancer activity. Halogenated 1,2,4-oxadiazoles were obtained from benzonitrile and coupled either lipophilic amines or with aminoalcohols. Lipophilic 1,3,4-oxadiazole derivatives were obtained through the Mannich reactions between 5-(aryl)-1,3,4-oxadiazole-2-thiol and alkylated or acylated amines. The in vitro cytotoxic effects were evaluated against 4T1– mammary carcinoma and CT26 – colon cancer cells. The best results were obtained for the 1,3,4-oxadiazole coupled to alkylated piperazine with 10–14 carbon chain moiety, with IC50 values ranging from 1.6 to 3.55μΜ for the 4T1 cell line, and from 1.6 to 3.9 μM for the CT26.WT cell line, and selectivity index up to 19. The most potent compounds were investigated with AnnexinV and PI staining as indicative of apoptosis induction.
Development of 1,2,4-Oxadiazoles as Potent and Selective Inhibitors of the Human Deacetylase Sirtuin 2: Structure–Activity Relationship, X-ray Crystal Structure, and Anticancer Activity
Moniot, Sébastien,Forgione, Mariantonietta,Lucidi, Alessia,Hailu, Gebremedhin S.,Nebbioso, Angela,Carafa, Vincenzo,Baratta, Francesca,Altucci, Lucia,Giacché, Nicola,Passeri, Daniela,Pellicciari, Roberto,Mai, Antonello,Steegborn, Clemens,Rotili, Dante
, p. 2344 - 2360 (2017/04/01)
Sirt2 is a target for the treatment of neurological, metabolic, and age-related diseases including cancer. Here we report a series of Sirt2 inhibitors based on the 1,2,4-oxadiazole scaffold. These compounds are potent Sirt2 inhibitors active at single-digit μM level by using the Sirt2 substrate a-tubulin-acetylLys40 peptide and inactive up to 100 μM against Sirt1, -3, and -5 (deacetylase and desuccinylase activities). Their mechanism of inhibition is uncompetitive toward both the peptide substrate and NAD+, and the crystal structure of a 1,2,4-oxadiazole analog in complex with Sirt2 and ADP-ribose reveals its orientation in a still unexplored subcavity useful for further inhibitor development. Tested in leukemia cell lines, 35 and 39 induced apoptosis and/or showed anti proliferative effects at 10 or 25 μM after 48 h. Western blot analyses confirmed the involvement of Sirt2 inhibition for their effects in NB4 and in U937 cells. Our results provide novel Sirt2 inhibitors with a compact scaffold and structural insights for further inhibitor improvement.
Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles
Cottrell, Denise M.,Capers, Jeffrey,Salem, Manar M.,DeLuca-Fradley, Kate,Croft, Simon L.,Werbovetz, Karl A.
, p. 2815 - 2824 (2007/10/03)
A series of 5-thiocyanatomethyl- and 5-alkyl-3-aryl-1,2,4-oxadiazoles were synthesized and evaluated for their activity against kinetoplastid parasites. Formation of the oxadiazole ring was accomplished through the reaction of benzamidoximes with acyl chlorides, while the thiocyanate group was inserted by reacting the appropriate 5-halomethyl oxadiazole with ammonium thiocyanate. The thiocyanate-containing compounds possessed low micromolar activity against Leishmania donovani and Trypanosoma brucei, while the 5-alkyl oxadiazoles were less active against these parasites. 3-(4-Chlorophenyl)-5-(thiocyanatomethyl)-1, 2,4-oxadiazole (compound 4b) displayed modest selectivity for L. donovani axenic amastigote-like parasites over J774 macrophages, PC3 prostate cancer cells, and Vero cells (6.4-fold, 3.8-fold, and 9.1-fold, respectively), while 3-(3,4-dichlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4h) showed 30-fold selectivity against Vero cells but was not selective against PC3 cells. In a murine model of visceral leishmaniasis, compound 4b decreased liver parasitemia caused by L. donovani by 48% when given in five daily i.v. doses at 5mg/kg and by 61% when administered orally for 5days at 50mg/kg. These results indicate that aromatic thiocyanates hold promise for the treatment of leishmanial infections if the selectivity of these compounds can be improved.
