- Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
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A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
- Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
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-
- Development of Novel (+)-Nootkatone Thioethers Containing 1,3,4-Oxadiazole/Thiadiazole Moieties as Insecticide Candidates against Three Species of Insect Pests
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To improve the insecticidal activity of (+)-nootkatone, a series of 42 (+)-nootkatone thioethers containing 1,3,4-oxadiazole/thiadiazole moieties were prepared to evaluate their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal evaluation revealed that most of the title derivatives exhibited more potent insecticidal activities than the precursor (+)-nootkatone after the introduction of 1,3,4-oxadiazole/thiadiazole on (+)-nootkatone. Among all of the (+)-nootkatone derivatives, compound 8c (1 mg/mL) exhibited the best growth inhibitory (GI) activity against M. separata with a final corrected mortality rate (CMR) of 71.4%, which was 1.54- and 1.43-fold that of (+)-nootkatone and toosendanin, respectively; 8c also displayed the most potent aphicidal activity against M. persicae with an LD50 value of 0.030 μg/larvae, which was closer to that of the commercial insecticidal etoxazole (0.026 μg/larvae); and 8s showed the best larvicidal activity against P. xylostella with an LC50 value of 0.27 mg/mL, which was 3.37-fold that of toosendanin and slightly higher than that of etoxazole (0.28 mg/mL). Furthermore, the control efficacy of 8s against P. xylostella in the pot experiments under greenhouse conditions was better than that of etoxazole. Structure-activity relationships (SARs) revealed that in most cases, the introduction of 1,3,4-oxadiazole/thiadiazole containing halophenyl groups at the C-13 position of (+)-nootkatone could obtain more active derivatives against M. separata, M. persicae, and P. xylostella than those containing other groups. In addition, toxicity assays indicated that these (+)-nootkatone derivatives had good selectivity to insects over nontarget organisms (normal mammalian NRK-52E cells and C. idella and N. denticulata fries) with relatively low toxicity. Therefore, the above results indicate that these (+)-nootkatone derivatives could be further explored as new lead compounds for the development of potential eco-friendly pesticides.
- Cheng, Wanqing,Fan, Jiangping,Guo, Yong,Han, Meiyue,Ma, Nannan,Yan, Xiaoting,Yang, Ruige
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p. 15544 - 15553
(2022/01/03)
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- Efficient formation of C–S bond using heterocyclic thiones and arynes
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Phenylthio heterocyclic compounds are widely used because of their diverse biological activities and medicinal prospects. Here, a facile method was reported. An arylation of 1,3,4-oxa(thia)diazol-2-thiones reacting with arynes to build C(aryl)-S bonds in the presence of CsF had good yields and excellent selectivity. The reaction was completed in short time without using expensive reagents and catalysts. Present reaction system is an efficient procedure to process phenylthio heterocyclic compounds and reveals a sustainable method and better application prospects in future organic synthesis.
- An, Yu,Xu, Gang,Cai, Menglu,Wang, Shihui,Wang, Xiao zhong,Chen, Yingqi,Dai, Liyan
-
-
- Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
- -
-
Paragraph 0055-0056; 0070; 0090; 0094; 0095; 0102
(2021/07/24)
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- The bioisosteric modification of pyrazinamide derivatives led to potent antitubercular agents: Synthesis via click approach and molecular docking of pyrazine-1,2,3-triazoles
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Tuberculosis remains as a major public health risk which causes the highest mortality rate globally and an improved regimen is required to treat the drug-resistant strains. Pyrazinamide is a first-line antitubercular drug used in combination therapy with other anti-TB drugs. Herein, we describe the modification of pyrazinamide structure using bioisosterism and rational approaches by incorporating the 1,2,3-triazole moiety. Three sets of pyrazine-1,2,3-triazoles (3a-o, 5a-o and 9a-l) are designed, synthesized and evaluated for their in vitro inhibitory potency against mycobacterium tuberculosis H37Rv. The pyrazine-1,2,3-triazoles synthesized through the bioisosteric modification displayed improved activity as compared to rationally modified pyrazine-1,2,3-triazoles. Among 42 title compounds, seven derivatives demonstrated significant anti-tubercular activity with the MIC of 1.56 μg/mL, which are two-fold more potent than the parent compound pyrazinamide. Further, the synthesized pyrazinamide analogs demonstrated moderate inhibition activity against several bacterial strains and possessed an acceptable in vitro cytotoxicity profile as well. Additionally, the activity profile of pyrazine-1,2,3-triazoles was validated by performing the molecular docking studies against the Inh A enzyme. Furthermore, in silico ADME prediction revealed good oral bioavailability for the potent molecules.
- Reddyrajula, Rajkumar,Dalimba, Udayakumar
-
supporting information
(2019/12/24)
-
- Antioxidant and tyrosinase docking studies of heterocyclic sulfide derivatives containing a thymol moiety
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Fourteen heterocyclic sulfide derivatives (4–17) containing a thymol moiety and oxadiazole, thiadiazole, triazole, oxazole, thiazole, imidazole, pyridine or purine heterocycles were synthesized in three steps. The cupric, Cu(II), ion reducing antioxidant capacity of the compounds was examined, and molecular docking studies were performed to determine whether the sulfur, thymol or heterocyclic moieties interact with the Cu ions in tyrosinase, a type-3 copper enzyme. Using the CUPRAC assay, eight compounds (5–8, 10, 15–17) showed equal or better Cu (II) reducing capacity than trolox at neutral pH, with trolox equivalent antioxidant capacity (TEAC) coefficients ranging between 1.00 and 1.48. The compounds containing a thiadiazole moiety were most effective, with the methyl thiadiazole derivative (8) having the highest Cu(II) reducing capacity. Molecular docking studies of the sulfide derivatives with tyrosinase revealed that there were no direct interactions between the sulfur atom and the active site copper ions. However, the compounds displayed two different binding interactions with the histidine-Cu catalytic center. For compounds 4–13, the thymol portion was embedded in the active site cavity, while for compounds 14–17 the heterocyclic portion of the molecule approached the cavity.
- Havasi, Mia H.,Ressler, Andrew J.,Parks, Eden L.,Cocolas, Alexander H.,Weaver, Ashton,Seeram, Navindra P.,Henry, Geneive E.
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- Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents
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Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33h, 33i, 42f and 42h showed strong potencies against all tested cell lines with IC50 values ranging from 14.63 to 49.90 μM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 μM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33h and 42f showed a significant reduction in TNF-α. Furthermore, compounds 33i and 42f exhibited significant elevation in CASP8 levels. Compounds 33i and 42f inhibited VEGF. In addition, compound 42f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42f, were performed. The results indicated that compound 42f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase.
- El-Zahabi, Mohamed Ayman,Sakr, Helmy,El-Adl, Khaled.,Zayed, Mohamed,Abdelraheem, Adel S.,Eissa, Sally I.,Elkady, Hazem,Eissa, Ibrahim H.
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- Synthesis of novel indole derivatives containing double 1,3,4-oxadiazole moiety as efficient bactericides against phytopathogenic bacterium Xanthomonas oryzae
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Abstract: A series of novel indole derivatives containing double 1,3,4-oxadiazole moiety was designed, synthesized and evaluated for their antibacterial activities in vitro. These compounds were fully characterized by 1H NMR, 13C NMR, and HRMS. Bioassay results indicated that most of title compounds exhibited excellent antibacterial activities against rice bacterial pathogen Xanthomonas oryzae (Xoo). For example, compounds 7d, 7h, 7i, 7j, 7k, 7l and 7m had the half-maximal effective concentration (EC50) values of 52.31, 54.12, 40.65, 38.80, 51.13, 52.75 and 50.66?μg/mL, respectively, which was better than that of commercial product bismerthiazol (BMT) (85.18?μg/mL). The experimental results proved that indole derivatives bearing double 1,3,4-oxadiazole unit are promising candidates for the development of new agricultural bactericides against pathogenic bacterium Xoo. Graphical abstract: [Figure not available: see fulltext.].
- Tian, Kun,Li, Xiao-Qin,Zhang, Li,Gan, Yi-Yuan,Meng, Jiao,Wu, Shou-Qun,Wan, Jin-Lin,Xu, Yang,Cai, Chao-Ting,Ouyang, Gui-Ping,Wang, Zhen-Chao
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- Rational Optimization and Action Mechanism of Novel Imidazole (or Imidazolium)-Labeled 1,3,4-Oxadiazole Thioethers as Promising Antibacterial Agents against Plant Bacterial Diseases
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The emergence and widespread occurrence of plant bacterial diseases that cause global production constraints have become major challenges to agriculture worldwide. To promote the discovery and development of new bactericides, imidazole-labeled 1,3,4-oxadiazole thioethers were first fabricated by integrating the crucially bioactive scaffolds of the imidazole motif and 1,3,4-oxadiazole skeleton in a single molecular architecture. Subsequently, a superior antibacterial compound A6 was gradually discovered possessing excellent competence against plant pathogens Xanthomonas oryzae pv oryzae and Xanthomonas axonopodis pv citri with EC50 values of 0.734 and 1.79 μg/mL, respectively. These values were better than those of commercial agents bismerthiazol (92.6 μg/mL) and thiodiazole copper (77.0 μg/mL). Further modifying the imidazole moiety into the imidazolium scaffold led to the discovery of an array of potent antibacterial compounds providing the corresponding minimum EC50 values of 0.295 and 0.607 μg/mL against the two strains. Moreover, a plausible action mechanism for attacking pathogens was proposed based on the concentration dependence of scanning electron microscopy, transmission electron microscopy, and fluorescence microscopy images. Given the simple molecular structures, easy synthetic procedure, and highly efficient bioactivity, imidazole (or imidazolium)-labeled 1,3,4-oxadiazole thioethers can be further explored and developed as promising indicators for the development of commercial drugs.
- Wang, Pei-Yi,Wang, Ming-Wei,Zeng, Dan,Xiang, Meng,Rao, Jia-Rui,Liu, Qing-Qing,Liu, Li-Wei,Wu, Zhi-Bing,Li, Zhong,Song, Bao-An,Yang, Song
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p. 3535 - 3545
(2019/03/26)
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- Antifungal benzo[b]thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles
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Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[b]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[b]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[b]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor.
- Kummari, Lalith K.,Butler, Mark S.,Furlong, Emily,Blundell, Ross,Nouwens, Amanda,Silva, Alberto B.,Kappler, Ulrike,Fraser, James A.,Kobe, Bostjan,Cooper, Matthew A.,Robertson, Avril A.B.
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p. 5408 - 5419
(2018/10/20)
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- Synthesis, spectral analysis and antibacterial evaluation of 5-substituted-1,3,4-oxadiazol-2-yl 4-(4-methylpiperidin-1-ylsulfonyl)benzyl sulfides
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Owing to valuable biological activities of 1,3,4-oxadiazole, sulfamoyl and piperidine functionalities, some new 1-(4-{[(5-substituted-1,3,4-oxadiazol-2-yl) thio]methyl}benzene sulfonyl)-4-methylpiperidine (6a-o) derivatives have been introduced. The target molecules were synthesized from different aralkyl/aryl carboxylic acids, 1a-o, through a series of steps. First the compounds, 1a-o, were converted to heterocyclic 1,3,4-oxadiazole nucleophiles, 4a-o. Second an electrophile as 1-(4-bromomethylbenzenesulfonyl)-4-methylpiperidine (5) was synthesized from 4-methylpiperidine. Finally the target compounds, 6a-o, were prepared by reacting 4a-o with 5 in DMF and LiH. The final compounds were structurally elucidated by spectral data of IR, 1H-NMR and EI-MS. All the compounds were screened for their antibacterial evaluation and found to exhibit valuable results.
- Aziz-Ur-Rehman,Ahtzaz, Samreen,Abbasi, Muhammad Athar,Siddiqui, Sabahat Zahra,Rasool, Shahid,Ahmad, Irshad
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p. 3370 - 3375
(2017/05/22)
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- Synthesis and biological activities of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors
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A series of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases have been conveniently synthesized in good yields. Their structures were characterized by IR,1H NMR,13C NMR and elemental analysis. The preliminary bioassay results indicated that some of the compounds showed promising in vitro fungicidal activities towards several test plant fungi; some of them exhibited significant herbicidal activities against Brassica campestris and excellent in vitro inhibitory activities against rice ketol-acid reductoisomerase (KARI). Among 14 novel compounds, 8c, 8d and 8m showed potent KARI inhibitory activities with Kivalue of (0.96?±?0.42), (3.86?±?0.49) and (3.10?±?0.71) μmol/L, respectively, and were comparable with IpOHA. These compounds could be novel KARI inhibitors for further investigation. The density functional theory (DFT) calculations and molecular docking were carried out to study the structure–activity relationship (SAR) of the active inhibitors in this Letter.
- Zhang, Yan,Liu, Xing-Hai,Zhan, Yi-Zhou,Zhang, Li-Yuan,Li, Zheng-Ming,Li, Yong-Hong,Zhang, Xiao,Wang, Bao-Lei
-
supporting information
p. 4661 - 4665
(2016/09/13)
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- 1,2,4-Triazolethione derivative containing (hetero)aryl group and piperazine, and preparation method and application thereof
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The invention discloses a 1,2,4-triazolethione derivative containing a (hetero)aryl group and piperazine, and a preparation method and an application thereof. The synthesis method has the advantages of few reaction steps, simple and mild conditions, simple operation and high yield. The derivative has a structural formula represented by general formula I and general formula II, and R, R and R in the general formula I and the general formula II are as defined in claim 1. The above compounds have certain in vitro inhibition activity to cucumber fusarium wilt, Cercospora arachidicola Hori, Macrophoma kawatsukai, Altemaria solani, Fusarium graminearum, Rhizoctonia cerealis and other plant pathogens, and especially have high in vitro inhibition activity on the cucumber fusarium wilt, Cercospora arachidicola Hori, Macrophoma kawatsukai and Rhizoctonia cerealis. The compounds of the general formula I and general formula II simultaneously have rice KARI enzyme in vitro inhibition activity. The derivative is suitable for comprehensive control of fungus damages on various crops.
- -
-
Paragraph 0043; 0044; 0045; 0046; 0047
(2016/10/07)
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- Piperazine-contained 1,3,4-oxadiazole Mannich base compound, and preparation and application thereof
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The invention discloses a piperazine-contained 1,3,4-oxadiazole Mannich base compound, and preparation and application thereof. The compound provided by the invention has the structural formulae shown in general formulae I and II, wherein in the formulae, R1 and R2 are defined according to Claim 1. The compound having the general formulae I and II has high-efficiency KARI enzyme restraining activity, higher weed control activity and particularly significance for activity of dicotyledon oilseed rape; meanwhile, the compound has a certain bactericidal activity, an in-vitro restraining activity for fusarium wilt of cucumber, mycosphaerella arachidicola, rhizoctonia cerealis, ceratobasidium cornigerum, alternaria solani, fusarium asiaticum and the like, and particularly significant effect on rhizoctonia cerealis. The piperazine-contained 1,3,4-oxadiazole Mannich base compound disclosed by the invention is applicable for efficient inhibition for KARI enzyme activity, and comprehensive control for weed and fungus damage on various crops.
- -
-
Paragraph 0018
(2016/10/09)
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- Synthesis and biological evaluation of new Mannich and Schiff bases containing 1,2,4-triazole and 1,3,4-oxadiazole nucleus
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5-(Pyridine-3-yl)-1,3,4-oxadiazole-2-thiole 2, obtaining starting from nicotinic acid hydrazide were converted to the corresponding Mannich bases (3a–c) by the reaction with several heterocyclic amines in the presence of formaldehyde. 1,2,4-Triazole-3-thi
- Ceylan, Sule
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p. 1958 - 1970
(2016/10/03)
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- Oxadiazoles and thiadiazoles: Novel α-glucosidase inhibitors
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Oxadiazoles and thiadiazoles 1-37 were synthesized and evaluated for the first time for their α-glucosidase inhibitory activities. As a result, fifteen of them 1, 4, 5, 7, 8, 13, 17, 23, 25, 30, 32, 33, 35, 36 and 37 were identified as potent inhibitors of the enzyme. Kinetic studies of the most active compounds (oxadiazoles 1, 23 and 25, and thiadiazoles 35 and 37) were carried out to determine their mode of inhibition and dissociation constants Ki. The most potent compound of the oxadiazole series (compound 23) was found to be a non-competitive inhibitor (Ki= 4.36 ± 0.017 μM), while most potent thiadiazole 35 was identified as a competitive inhibitor (Ki= 6.0 ± 0.059 μM). The selectivity and toxicity of these compounds were also studied by evaluating their potential against other enzymes, such as carbonic anhydrase-II and phosphodiesterase-I. Cytotoxicity was evaluated against rat fibroblast 3T3 cell line. Interestingly, these compounds were found to be inactive against other enzymes, exhibiting their selectivity towards α-glucosidase. Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. α-Glucosidase inhibitors can also be used as anti-obesity and anti-viral drugs. Our study identifies two novel series of potent α-glucosidase inhibitors for further investigation.
- Kashtoh, Hamdy,Hussain, Shafqat,Khan, Ajmal,Saad, Syed Muhammad,Khan, Jalaluddin A.J.,Khan, Khalid Mohammed,Perveen, Shahnaz,Choudhary, M. Iqbal
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p. 5454 - 5465
(2015/02/02)
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- Diaryl-Substituted Azolylthioacetamides: Inhibitor Discovery of New Delhi Metallo-β-Lactamase-1 (NDM-1)
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The emergence and spread of antibiotic-resistant pathogens is a global public health problem. Metallo-β-lactamases (MβLs) such as New Delhi MβL-1 (NDM-1) are principle contributors to the emergence of resistance because of their ability to hydrolyze almost all known β-lactam antibiotics including penicillins, cephalosporins, and carbapenems. A clinical inhibitor of MBLs has not yet been found. In this study we developed eighteen new diaryl-substituted azolylthioacetamides and found all of them to be inhibitors of the MβL L1 from Stenotrophomonas maltophilia (KiiiII ion(s) preferentially via the triazole moiety, while other moieties interact mostly with the conserved active site residues Lys224 (CcrA, NDM-1, and ImiS) or Ser221 (L1).
- Zhang, Yi-Lin,Yang, Ke-Wu,Zhou, Ya-Jun,LaCuran, Alecander E.,Oelschlaeger, Peter,Crowder, Michael W.
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p. 2445 - 2448
(2015/08/24)
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- ZnCl2 catalyzed efficient synthesis of 1,3,4-oxadiazole and 1,3,4-thiadiazole
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New methods for the synthesis of 1,3,4-oxadiazole and 1,3,4-thiadiazole have been described. No cyclizations took place in the absence of ZnCl 2. 1,3,4-Thiadiazoles are formed in the presence of ZnCl2 alone, whereas oxadiazoles are produced when a base such as Et3N or KOH was used along with ZnCl2. % Yields are optimized.
- Rahman, Md.A.,Karim, Mohammad R.,Arifuzzaman, Md.,Siddiquee, Tasneem A.,Mirza, Aminul H.
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p. 3267 - 3273
(2014/06/09)
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- Synthesis, biological evaluation and QSAR study of a series of substituted quinazolines as antimicrobial agents
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A novel series of 1-N-substituted-3-(4-(5-(pyridin-3-yl)-1,3,4-oxadiazol-2- ylthio)quinazolin-6-yl)urea/thiourea derivatives (6a-6r) and 1-N-substituted-3-(7-(4-methylpiperazin-1-yl)-4-(5-(pyridin-3-yl)-1,3, 4-oxadiazol-2-ylthio)quinazolin-6-yl)urea/thiourea derivatives (14a-14s) were synthesized and screened for antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli. Biological results indicated that the synthesized compounds showed a broad-spectrum activity against tested microorganisms at MIC values between 6.25 and 100 μg/mL. Compound 6r showed a broad spectrum of activity and was found to be active against all tested species. A quantitative structure-activity relationship study has been carried out on the synthesized compounds to get better insights into pharmacophoric features responsible for the antibacterial activity. Genetic function approximation technique was used to identify descriptors that influence biological activity. Hydrophobic (AlogP98), electronic (atomic polarizability), and topological (radius of gyration) descriptors were found to affect the activity significantly. Generated model was found to be statistically significant (r 2 = 0.86, predictive index = 0.96) and predictive as indicated by very low residuals in internal and external cross-validation.
- Buha, Vipul M.,Rana, Dharmaraj N.,Chhabria, Mahesh T.,Chikhalia, Kishor H.,Mahajan, Bhushan M.,Brahmkshatriya, Pathik S.,Shah, Nisha K.
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p. 4096 - 4109
(2013/09/02)
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- Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents
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A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.
- Du, Qian-Ru,Li, Dong-Dong,Pi, Ya-Zhou,Li, Jing-Ran,Sun, Jian,Fang, Fei,Zhong, Wei-Qing,Gong, Hai-Bin,Zhu, Hai-Liang
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p. 2286 - 2297
(2013/05/09)
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- Synthesis and biological evaluation of nonsymmetrical aromatic disulfides as novel inhibitors of acetohydroxyacid synthase
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46 Novel nonsymmetrical aromatic disulfides containing [1,3,4]thiadiazole or [1,3,4]oxadiazole groups were synthesized and their biological activities were evaluated as inhibitors of acetohydroxyacid synthase (AHAS, EC 2.2.1.6). Besides their strong in vitro inhibition against plant AHAS, compounds 3e and 3f also display 80-100% post-emergence herbicidal activities in greenhouse bioassay at 1500 g/ha dosage. The assay of exogenous branched-chain amino acids supplementation on rape root growth of 3e suggests that the herbicidal activity has relationship with AHAS inhibition.
- Li, Zai-Shun,Wang, Wei-Min,Lu, Wei,Niu, Cong-Wei,Li, Yong-Hong,Li, Zheng-Ming,Wang, Jian-Guo
-
supporting information
p. 3723 - 3727
(2013/07/25)
-
- 2-(Quinolin-4-ylthio)-1,3,4-oxadiazole derivatives: Design, synthesis, antibacterial and antifungal studies
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A series of novel hybrid 2-(7-chloroquinolin-4-ylthio)-5-(substituted)-1,3, 4-oxadiazole derivatives have been designed, synthesized which contains different pharmacophores like quinoline and 1,3,4-oxadiazole linked via sulfur atom. All the newly synthesized derivatives have been characterized by IR, 1H NMR, 13C NMR spectral and elemental analysis. Further, All the final synthesized scaffolds have been subjected to in vitro antimicrobial activity against several bacteria (E.coli, P.aeruginosa, S.aureus, S.pyogenus) and fungi (C.albicans, A.niger, A.clavatus) using broth dilution technique. Among the compounds tested, compounds 3f substituted with coumarin analogue and 3b with amine group at second position of phenyl to oxadiazole moiety are found to be most potent.
- Modh, Rahul P,Shah, Dhruvin,Chikhalia, Kishor H
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p. 1318 - 1324
(2014/01/06)
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- Calix[4]arene based 1,3,4-oxadiazole and thiadiazole derivatives: Design, synthesis, and biological evaluation
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In the present investigation, we describe some novel calixarene based heterocyclic compounds (5a-5i) in which 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives have been coupled with 5,11,17,23-tetra-tert-butyl-25,27- bis(chlorocarbonyl-methoxy)-26,28-dihydroxy calix[4]arene. All the newly synthesized calixarene based heterocyclic compounds have been characterized by elemental analysis and various spectroscopic methods like FTIR, 1H NMR, 13C NMR, and FAB-MS. All the final scaffolds have been subjected to antioxidant activity, in vitro antimicrobial screening against two gram (+ve) bacteria (S. aureus, S. pyogenes), two gram (-ve) bacteria (E. coli, P. aeruginosa) and two fungal strains (C. albicans, A. clavatus) and also have been screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv.
- Patel, Manishkumar B.,Modi, Nishith R.,Raval, Jignesh P.,Menon, Shobhana K.
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experimental part
p. 1785 - 1794
(2012/04/23)
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- Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring
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Novel thiazolidinedione derivatives were synthesized by incorporating pharmacologically significant heterocycles viz, substituted thiazole, triazole, and oxadiazole moieties linked to the central phenyl ring via heteroatomlinkage with one/two carbon spacer as the structural analogs of Pioglitazone by employing multistep synthetic protocols. Structures of all the newly synthesized intermediates and target molecules were established by analytical and spectral data. These newly synthesized compounds were screened for their invivo hypoglycemic and hypolipidemic activities in male wistar rats. Some of the synthesized compounds demonstrated good activity.
- Mohammed Iqbal,Khan, Ashraf Y.,Kalashetti, Mallikarjun B.,Belavagi, Ningaraddi S.,Gong, Young-Dae,Khazi, Imitiyaz Ahmed M.
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body text
p. 308 - 315
(2012/08/08)
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- Propylene oxide assisted one-pot, tandem synthesis of substituted-1,3,4- oxadiazole-2(3H)-ones in water
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It has been developed for the synthesis of substituted-1,3,4-oxadiazole- 2(3H)-one derivatives via a novel one-pot, tandem procedure assisted by propylene oxide. The 5-substitued-1,3,4-oxadiazole-2(3H)-ones and 3,5-disubstitued-1,3,4-oxadiazole-2(3H)-ones were, respectively, obtained from three-component reaction of acylhydrazines, carbon disulfide, and propylene oxide, and four-component reaction of acylhydarazines, carbon disulfide, propylene oxide, and organic halides. The reactions were carried out using water as solvent in the presence of potassium phosphate to afford the expected products in good to excellent yields.
- Yan, Xu,Zhou, Shuo,Wang, Yuanqiang,Ge, Zemei,Cheng, Tieming,Li, Runtao
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experimental part
p. 7978 - 7983
(2012/09/21)
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- Design, synthesis and biological evaluation of 1,3,4-oxadiazole derivatives
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3D QSAR analysis for the 21 molecules of 1,3,4-oxadiazoles was carried out by using k-Nearest Neighbor Molecular Field Analysis (kNN-MFA) combined with various selection procedures. 30 3D QSAR models were generated; one of these models was selected on the basis of q2 and pred-r2 values. The selected Model has training set of 17 molecules and test set of 4 molecules with validation (q2) and cross validation (pred-r2) values of 0.6969 and 0.6148 respectively. Title compounds of 1,3,4-oxadiazole derivatives were synthesized by the ring closure reactions of various acylhydrazides with carbon disulphide (4a-e) and with aromatic acids in POCl3 (5a-e). After structural elucidation, all the synthesized compounds were evaluated for their antimicrobial activity against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis.
- Jha, Keshari Kishore,Samad, Abdul,Kumar, Yatendra,Shaharyar, Mohd.,Khosa, Ratan Lal,Jain, Jainendra,Kumar, Vikash,Singh, Priyanka
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experimental part
p. 4963 - 4967
(2010/11/18)
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- A new method of reducing 2-mercapto-substituted 1,3,4-oxadizoles: Synthesis of acylhydrazine derivatives
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A new method has been developed for the synthesis of acylhydrazines 5a-g by the reduction of unsymmetrical 1,3,4-oxadiazoles 4a-g by using sodium borohydride/acetic acid combination. Later on, acylhydrazines 5a-g were converted to their corresponding sulfonamide derivatives 6a-d.
- Zareefa, Muhammad,Iqbal, Rashid,Zaidi, Javid Hussain,Arfan, Muhammad,Ali, Muhammad,Khan, Khalid M.
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scheme or table
p. 411 - 414
(2011/03/23)
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- Synthesis and characterization of mono- and bicyclic heterocyclic derivatives containing 1,2,4-triazole, 1,3,4-thia-, and -oxadiazole rings
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A series of new N- and S-substituted 1,3,4-oxadiazole derivatives were synthesized. 5-Pyridin-3-yl-3-[2-(5-thioxo-4,5-dihydro-l,3,4-thiadiazol-2-yl) ethyl]-1,3,4-oxadiazole-2(3H)-thione and 5-[(5-(pyridin-3-yl)-1,3,4-oxadiazol-2- ylthio)methyl]-N-phenyl-1
- El-Sayed, Wael A.,Hegab, Mohamed I.,Tolan, Hala E. M.,Abdel-Rahman, Adel A.-H.
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experimental part
p. 1055 - 1060
(2009/12/05)
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- OXADIAZOLE AND THIADIAZOLE COMPOUNDS AND THEIR USE AS NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS
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This invention relates to oxadiazolyl and thiadiazolyl derivatives, which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.
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Page/Page column 19
(2008/12/05)
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- Synthesis and structure determination of some oxadiazole-2-thione and triazole-3-thione galactosides
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The syntheses of 5-pyridyl-3(β-D-galactopyranosyl)-1,3,4-oxadiazole-2-thiones 3a-3c and 5-pyridyl-2(β-D-galactopyranosyl)-4-benzyl-l,2, 4-triazole-3-thiones 6a-6c are reported. The existence of N-galactosides - not S-galactosides - was proven by IR and 15N NMR spectroscopy. The structures of the final products and the intermediates were elucidated by IR, 1H, 13C and 15N NMR spectroscopy and mass spectrometry.
- Ahmad, Roshan,Iqbal, Rashid,Akhtar, Humaira,Duddeck, Helmut,Stefaniak, Lech,Sitkowski, Jerzy
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p. 1671 - 1682
(2007/10/03)
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- Studies on the synthesis and biological activity of 3-arylaminomethyl-5-(3-pyridyl)- 1,3,4-oxadiazole-2-thione derivatives
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Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences, Mangalore, INDIA. 3-arylaminomethyl-5-(3-pyridyl)-1,3,4-oxadiazole-2-thiones were prepared by reaction of 5-(3-pyridyl)-1,3,4-oxadiazole-2-thione with formaldehyde and appropriate alky and aryl amines in ethanol, as potential biological active agents. These new synthesized Mannich bases were screened for their antimicrobial, antifungal and antiinflammatory activities.
- Satyanarayana,Gorge,Subrahmanyam,Kalluraya
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p. 228 - 232
(2007/10/03)
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- Novel inhibitors of cell adhesion molecule expression
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2-Alkylsulfinyl-1,3,4-oxadiazoles have been identified as novel inhibitors of cell adhesion molecule expression on endothelial cells. These compounds have been shown to inhibit the up-regulation of ELAM-1 and VCAM-1 on activated human umbilical vein endothelial cells (HUVECs) as measured by ELISA.
- Dodd, Dharmpal S.,Shen, Zhongqi,Nishi, Takao,Graber, Norma,Bealls, Dawson,Fong, Miranda,Ebert, Tracy
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p. 2693 - 2698
(2007/10/03)
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- 2-mercapto-5-pyridyl-1,3,4-oxadiazoles and 2-mercapto-5-pyridyl-1,3,4-thiadiazoles of the formula I
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The invention relates to 2-mercapto-5-pyridyl-1,3,4-oxadiazoles and 2-mercapto-5-pyridyl-1,3,4-thiadiazoles of the formula I STR1 wherein X is oxygen or sulfur, R' is C1 -C3 alkyl which is substituted by bromine, fluorine, C1 -C3 alkoxy or cyano; unsubstituted or halogen-substituted C3 -C7 alkenyl; unsubstituted or halogen-substituted C4 -C7 alkynyl, R is C1 -C3 alkyl, unsubstituted C1 -C3 alkoxy or C1 -C3 alkoxy which is substituted by halogen or C1 -C3 alkoxy; unsubstituted or halogen-substituted C3 -C7 alkenyl; C3 -C7 alkynyl, C1 -C3 alkylthio, halogen, cyano, hydroxy, amino or amino which is substituted by one or two C1 -C3 alkyl groups; or is aminocarbonyl; and n is 0, 1, 2, 3 or 4, to the preparation of the compounds of formula I and to novel intermediates for the synthesis of these compounds. The compounds of formula I have nematicidal properties. The invention further relates to nematicidal compositions which contain at least one compound of formula I as active component, and to methods of using said compounds and of the compositions containing them for controlling nematodes.
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