- Synthesis, in silico, and in vitro evaluation of anti-leishmanial activity of oxadiazoles and indolizine containing compounds flagged against anti-targets
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Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 μM on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents.
- Stevanovic, Strahinja,Sencanski, Milan,Danel, Mathieu,Menendez, Christophe,Belguedj, Roumaissa,Bouraiou, Abdelmalek,Nikolic, Katarina,Cojean, Sandrine,Loiseau, Philippe M.,Glisic, Sanja,Baltas, Michel,García-Sosa, Alfonso T.
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Read Online
- Syntheses and biological activity of platinum(II) and palladium(II) complexes with phenyl-oxadiazole-ethylenediamine ligands
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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.
- 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
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p. 823 - 837
(2021/01/20)
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- Synthesis and Evaluation of Antibacterial Activity of 1,2,4-Oxadiazole-Containing Biphenylcarboxylic Acids
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Abstract: A one-pot method for the synthesis of biphenylcarboxylic acids containing 1,2,4-oxadiazole ring in the NaOH–DMSO system was developed. The results of in vitro experiments showed that the synthesized compounds exhibit antibacterial activity against susceptible strains of E. coli and S. aureus.
- Baikov, S. V.,Presnukhina, S. I.,Shetnev, A. A.,Tarasenko, M. V.
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p. 1611 - 1619
(2020/10/15)
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- Synthesis and Properties of Energetic 1,2,4-Oxadiazoles
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The synthesis and characterization of a series of 3,5-di-aryl-1,2,4-oxadiazoles are reported and the effects of nitro groups in the aromatic rings on the experimental heats of decomposition (ΔHd) and heats of combustion (ΔHc) are evaluated. Heats of formation (ΔHf) and densities (ρ) were calculated and correlations between ΔHd and ΔHf were assessed for these compounds. Experimental determination of ρ (by gas pycnometry) on a selection of the compounds led to the calculation of detonation velocity (VD), detonation pressure (PD) and specific impulse (ISP) parameters by the Explo 5 program. An X-ray analysis of compound (4i) confirmed the structure and showed a crystal density (at 120 K) close to that determined by gas pycnometry.
- Wang, Zuoquan,Zhang, Hong,Jabeen, Farukh,Gopinathan-Pillai, Girinath,Arami, Justin A.,Killian, Benjamin J.,Stiegler, Kelcie D.,Yudewitz, Dalia S.,Thiemann, Pauline L.,Turk, Jessica D.,Zhou, Wenfeng,Steel, Peter J.,Hall, C. Dennis,Katritzky, Alan R.
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p. 7468 - 7474
(2016/01/25)
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- Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents
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Abstract In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl ketone analogues have been designed and synthesized. The synthesized compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against three human cancer cell lines including A549, NCI-H661, and U937. Most analogues exhibited higher antiproliferative activities against human acute myeloid leukemia cell U937 than the other two human lung cancer cell lines. Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms. Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these compounds might have potential as lead compounds for the development of anti-tumor drugs with HDACs inhibitory activities.
- Cai, Jin,Wei, Hongtao,Hong, Kwon Ho,Wu, Xiaoqing,Zong, Xi,Cao, Meng,Wang, Peng,Li, Lushen,Sun, Chunlong,Chen, Bo,Zhou, Gaoxing,Chen, Junqing,Ji, Min
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p. 3457 - 3471
(2015/08/03)
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- One-pot synthesis of amidoxime via Pd-catalyzed cyanation and amidoximation
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A novel "one-pot" reaction was developed for the synthesis of aryl or heteroaryl-substituted amidoxime compounds containing various functional groups. Fluorescence titration experiments coupled with theoretical analysis revealed that the steric hindrance and electronic effects of substituents influence the binding ability of the amidoxime compounds to uranyl ions. This journal is
- Yang, Chu-Ting,Han, Jun,Liu, Jun,Gu, Mei,Li, Yi,Wen, Jun,Yu, Hai-Zhu,Hu, Sheng,Wang, Xiaolin
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supporting information
p. 2541 - 2545
(2015/04/14)
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- PYRROLOTRIAZINE KINASE INHIBITORS
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 43
(2015/04/28)
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- IMIDAZOPYRIDAZINE KINASE INHIBITORS USEFUL TO TREATING A DISEASE OR DISORDER MEDIATED BY AAK1, SUCH AS ALZHEIMER'S DISEASE, BIPOLAR DISORDER, PAIN, SCHIZOPHRENIA
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 28
(2015/03/13)
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- COMPOUNDS AND METHODS for the inhibition of HDAC
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Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, Z, L and n are as defined herein, and methods of making and using the same.
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Paragraph 0134-0135; 0479-0480
(2015/11/24)
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- Design, synthesis and biological activity evaluation of 2,5-diphenyl-1,3,4-oxadiazole derivatives as novel inhibitors of fructose-1,6-bisphosphatase
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Fructose-1,6-bisphosphatase (FBPase), an important gluconeogenic enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate. The effort to discover new FBPase inhibitors was carried out by high-throughput screening (HTS) of a library of 56,000 lead-like compounds, and a 2,5-diphenyl-1,3,4-oxadiazole (3a, IC50 = 15.45 μM) which bearing no phosphate group was identified as a potential FBPase inhibitor for the first time. Structure-activity-relationship (SAR) research of a series of analogues obtained by modifying the substituent groups and replacing the 1,3,4-oxadiazole with several other heterocycles disclosed the key structure and substituent groups related to the binding with FBPase.
- He, Hai-Bing,Gao, Li-Xin,Zhou, Yue-Yang,Liu, Ting,Tang, Jie,Gong, Xue-Ping,Qiu, Wen-Wei,Li, Jing-Ya,Li, Jia,Yang, Fan
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p. 2693 - 2712
(2013/01/15)
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- Acetic acid aldose reductase inhibitors bearing a five-membered heterocyclic core with potent topical activity in a visual impairment rat model
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A number of 1,2,4-oxadiazol-5-yl-acetic acids and oxazol-4-yl-acetic acids were synthesized and tested for their ability to inhibit aldose reductase (ALR2). The oxadiazole derivatives, 7c, 7f, 7i, and 8h, 8i, proved to be the most active compounds, exhibiting inhibitory levels in the submicromolar range. In this series, the phenyl group turned out to be the preferred substitution pattern, as its lengthening to a benzyl moiety determined a general reduction of the inhibitory potency. The lead compound, 2-[3-(4-methoxyphenyl)-1,2,4- oxadiazol-5-yl]acetic acid, 7c, showed an excellent in vivo activity, proving to prevent cataract development in severely galactosemic rats when administered as an eye-drop solution in the precorneal region of the animals. Computational studies on the ALR2 inhibitors were performed to rationalize the structure-activity relationships observed and to provide the basis for further structure-guided design of novel ALR2 inhibitors.
- La Motta, Concettina,Sartini, Stefania,Salerno, Silvia,Simorini, Francesca,Taliani, Sabrina,Marini, Anna Maria,Da Settimo, Federico,Marinelli, Luciana,Limongelli, Vittorio,Novellino, Ettore
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supporting information; experimental part
p. 3182 - 3193
(2009/04/06)
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- Oxadiazoles and their manufacture
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An oxadiazole compound and process of making same, is represented by Formula I: wherein R1 represents a substituted or unsubstituted straight, branched, or cyclo-alkyl group having at least two carbon atoms, and R2 represents an alkyl, aryl, or heteroaryl group.
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Page/Page column 5
(2008/06/13)
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- Method for preparation of N-pyrazolylamidoximes
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A method for the preparation of N-pyrazolylamidoximes of the general formula I R1 and R2 independently represent an alkyl, aryl, or heteroaryl group, comprises reacting a 5-(β-ketoalkyl)-3-substituted-1,2,4-oxadiazoles of the general formula II with hydrazine.
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Page/Page column 4
(2008/06/13)
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- Synthesis of 3,5-disubstituted-1,2,4-oxadiazoles using tetrabutylammonium fluoride as a mild and efficient catalyst
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Tetrabutylammonium fluoride (TBAF) was found to be a mild and efficient catalyst for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles. Using 0.1 - 1.0 equivalents of TBAF in THF for 1 - 24 h at room temperature, alkanoyl- and aroyloxyamidines were converted in high yield to the corresponding 3,5-disubstituted-1,2,4-oxadiazoles. A variety of R and R′ substituents were investigated.
- Gangloff, Anthony R.,Litvak, Joane,Shelton, Emma J.,Sperandio, David,Wang, Vivian R.,Rice, Kenneth D.
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p. 1441 - 1443
(2007/10/03)
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- Synthesis and reactivity of carbohydroximoyl azides: I. Aliphatic and aromatic carbohydroximoyl azides and 5-substituted 1-hydroxytetrazoles based thereon
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Chlorination of 1-hydroxyiminopentane gave 1-chloro-1-nitrosopentane which reacted with sodium azide in DMF to form pentanohydroximoyl azide. The azidation of benzohydroximoyl chlorides was always accompanied by decomposition to benzonitriles. Treatment of carbohydroximoyl azides in ether with gaseous hydrogen chloride afforded 5-butyl-and 5-aryl-1-hydroxytetrazoles which reacted with acetic anhydride to form the corresponding acetates.
- Tselinskii,Mel'nikova,Romanova
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p. 430 - 436
(2007/10/03)
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- Kinetics of methanolysis of substituted benzamide O-(phenoxycarbonyl)- and O-(alkoxycarbonyl)oximes catalyzed by sodium methanolate
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The kinetics of methanolysis of substituted benzamide O-(phenoxycarbonyl)-and O-(alkoxycarbonyl)oximes catalyzed by sodium methanolate was studied at 25 °C. The reaction proceeds in two steps. In the first, faster step, the substituted phenoxy group is exchanged for a methoxy group giving rise to substituted O-(methoxycarbonyl)oximes. In the second step, a benzamide oxime is eliminated and dimethyl carbonate is formed. The slope of the plot of the rate constant in dependence on the sodium methanolate concentration has an increasing tendency in both steps. In the presence of 18-crown-6, the plots are linear and the rate constants are lower than in the absence of the crown ether. The rate constants of the reaction of the substrate with the methanolate ion and with the MeONa ion pair were determined assuming that the sodium cation-catalyzed reactions constitute the rate-determining step of the reaction of the substrate with the MeONa ion pair. For the elimination of the aryloxy group and of the substituted benzamide oxime, the rate constants of the reaction with the ion pair are roughly twelvefold and twentyfold higher, respectively, than in the uncatalyzed reaction. The slope of the dependence of log k on the pKa of the substituted phenols (β1g) has the value of -0.52 for the uncatalyzed reaction of elimination of the substituted phenoxy group, -0.83 for the elimination of the benzamide oxime group, and -0.53 for the reaction with the ion pair. In the first step and probably also in the second step, the reaction proceeds by the concerted mechanism. The relatively high ρ value of methanolysis of substituted benzamide O-(4-nitrophenoxycarbonyl)oximes, 0.63, suggests that the structure of the transition state approaches that of the tetrahedral intermediate.
- Dusek, Libor,Kavalek, Jaromir,Sterba, Vojeslav
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p. 265 - 287
(2007/10/03)
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- A new method for the synthesis of nitriles enriched with the 15N isotope
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A new synthetic method for the preparation of 15N-labeled nitriles from nonlabeled nitriles is proposed. - Key words: 15N isotope; nitriles; amidoximes.
- Yarovebko, V. N.,Krayushkin, M. M.,Lysenko, O. V.,Kustov, L. M.,Zavarzin, I. V.
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p. 402 - 404
(2007/10/02)
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- Syntheses based on nitrile oxides. 3. Interaction of aromatic nitrile oxides with bis-trimethylsilylthiodiimide
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Interaction of aromatic nitrile oxides with bis-trimethylsilylthiodiimide results in 2-amino-4-aryl-1,2,3,5-oxathiadiazoles, the first representatives of a new class of heterocyclic compounds.
- Ogurtsov, V. A.,Rakitin, O. A.,Strelenko, Yu. A.,Obruchnikova, N. V.,Khmel'nitskii, L. I.
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p. 706 - 708
(2007/10/02)
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