- Synthesis, spectral analysis, antibacterial, antifungal, antioxidant and hemolytic activity studies of some new 2,5-disubstituted-1,3,4-oxadiazoles
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Series of 1,3,4-oxadiazole derivatives (5a–5g and 5h, 5i) were synthesized and characterized by FT-IR, 1H NMR, 13C NMR and HR-MS spectral analysis. All the target compounds were screened for their in vitro antibacterial activity against two Gram-negative bacterial strains namely Escherichia coli (MTCC 405) and Salmonella typhi (MTCC 3224) and two Gram-positive bacterial strains namely Bacillus subtilis (MTCC 1790) and Bacillus megaterium (MTCC 1684) and antifungal activity against Aspergillus niger (MTCC 282), Rhizopus oryzae (MTCC 262), Penicillium chrysogenum (MTCC 974), and Candida albicans (MTCC 183) fungal strains. The synthesized compounds exhibited significant antibacterial and antifungal potential. Three compounds (5e, 5f and 5g) have shown higher antibacterial activity with very low MIC values comparable to streptomycin. According to the SAR study, the antibacterial efficacy can be intensified by substituting fluoro and methyl substituents at the para position in acid hydrazide. The synthesized compounds were also screened for % radical scavenging activity by OH and DPPH assay and found to be good antioxidant agents. Besides, the hemolytic study revealed that the synthesized 1,3,4-oxadiazoles possessed negligible cytotoxicity compared with the standard.
- Adole, Vishnu A.,Chobe, Santosh S.,Dhonnar, Sunil L.,Jagdale, Bapu S.,More, Rahul A.,Sadgir, Nutan V.
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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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- Design, Synthesis, and Study of the Insecticidal Activity of Novel Steroidal 1,3,4-Oxadiazoles
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A series of novel steroidal derivatives with a substituted 1,3,4-oxadiazole structure was designed and synthesized, and the target compounds were evaluated for their insecticidal activity against five aphid species. Most of the tested compounds exhibited potent insecticidal activity against Eriosoma lanigerum (Hausmann), Myzus persicae, and Aphis citricola. Compounds 20g and 24g displayed the highest activity against E. lanigerum, showing LC50 values of 27.6 and 30.4 μg/mL, respectively. Ultrastructural changes in the midgut cells of E. lanigerum were detected by transmission electron microscopy, indicating that these steroidal oxazole derivatives might exert their insecticidal activity by destroying the mitochondria and nuclear membranes in insect midgut cells. Furthermore, a field trial showed that compound 20g exhibited effects similar to those of the positive controls chlorpyrifos and thiamethoxam against E. lanigerum, reaching a control rate of 89.5% at a dose of 200 μg/mL after 21 days. We also investigated the hydrolysis and metabolism of the target compounds in E. lanigerum by assaying the activities of three insecticide-detoxifying enzymes. Compound 20g at 50 μg/mL exhibited inhibitory action on carboxylesterase similar to the known inhibitor triphenyl phosphate. The above results demonstrate the potential of these steroidal oxazole derivatives to be developed as novel pesticides.
- Bai, Hangyu,Jiang, Weiqi,Li, Qi,Li, Tian,Ma, Shichuang,Shi, Baojun,Wu, Wenjun
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p. 11572 - 11581
(2021/10/12)
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- Design, synthesis and pharmacological evaluation of tricyclic derivatives as selective RXFP4 agonists
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Relaxin family peptide receptors (RXFPs) are the potential therapeutic targets for neurological, cardiovascular, and metabolic indications. Among them, RXFP3 and RXFP4 (formerly known as GPR100 or GPCR142) are homologous class A G protein-coupled receptors with short N-terminal domain. Ligands of RXFP3 or RXFP4 are only limited to endogenous peptides and their analogues, and no natural product or synthetic agonists have been reported to date except for a scaffold of indole-containing derivatives as dual agonists of RXFP3 and RXFP4. In this study, a new scaffold of tricyclic derivatives represented by compound 7a was disclosed as a selective RXFP4 agonist after a high-throughput screening campaign against a diverse library of 52,000 synthetic and natural compounds. Two rounds of structural modification around this scaffold were performed focusing on three parts: 2-chlorophenyl group, 4-hydroxylphenyl group and its skeleton including cyclohexane-1,3-dione and 1,2,4-triazole group. Compound 14b with a new skeleton of 7,9-dihydro-4H-thiopyrano[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-8(5H)-one was thus obtained. The enantiomers of 7a and 14b were also resolved with their 9-(S)-conformer favoring RXFP4 agonism. Compared with 7a, compound 9-(S)-14b exhibited 2.3-fold higher efficacy and better selectivity for RXFP4 (selective ratio of RXFP4 vs. RXFP3 for 9-(S)-14b and 7a were 26.9 and 13.9, respectively).
- Lin, Lin,Lin, Guangyao,Zhou, Qingtong,Bathgate, Ross A.D.,Gong, Grace Qun,Yang, Dehua,Liu, Qing,Wang, Ming-Wei
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supporting information
(2021/03/16)
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- Design, synthesis, and evaluation of N-benzylpyrrolidine and 1,3,4-oxadiazole as multitargeted hybrids for the treatment of Alzheimer's disease
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Novel N-Benzylpyrrolidine hybrids were designed, synthesized, and tested against multiple in-vitro and in-vivo parameters. Among all the synthesized molecules, 8f and 12f showed extensive inhibition against beta-secretase-1 (hBACE-1), human acetylcholinesterase (hAChE) & human butyrylcholinesterase (hBuChE). These molecules are also endowed with significant AChE-peripheral anionic site (PAS) binding capability, blood-brain barrier permeability, potential disassembly of Aβ aggregates along with neuroprotection ability on SHSY-5Y cell lines. Results of the Y-Maze and Morris water maze test concluded that compounds 8f and 12f ameliorated cognitive dysfunction induced by scopolamine and Aβ. The ex-vivo activity was executed on rat's brain homogenate indicating a reduction in AChE level and oxidative stress. The pharmacokinetic investigation ascertained considerable oral absorption profile of the lead 12f. The results of the in silico docking studies and molecular dynamics simulations demonstrated stable interactions of compounds 8f and 12f with the target residues of hAChE, hBuChE and hBACE-1.
- Choubey, Priyanka Kumari,Tripathi, Avanish,Tripathi, Manish Kumar,Seth, Ankit,Shrivastava, Sushant Kumar
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- Synthesis, biological evaluation of benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety as potential anti-oxidant and anti-inflammatory agents
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Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+[rad] bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.
- Bai, Xue-Qian,Cui, Ming-Yue,Li, Chun-Shi,Liang, Cheng-Wu,Song, Ze-Wen,Wang, Hui-Yan,Zhang, Tian-Yi,Zheng, Xian-Jing
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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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- Design and synthesis of new norfloxacin-1,3,4-oxadiazole hybrids as antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)
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Toward the search of new antibacterial agents to control methicillin-resistant Staphylococcus aureus (MRSA), a class of new norfloxacin-1,3,4-oxadiazole hybrids were designed and synthesized. Antibacterial activities against drug-sensitive bacteria S. aureus and clinical drug resistant isolates of MRSA were evaluated. Compound 5k exhibited excellent antibacterial activities against S. aureus (MIC: 2 μg/mL) and MRSA1–3 (MIC: 0.25–1 μg/mL). The time-kill kinetics demonstrated that compound 5k had an advantage over commonly used antibiotics vancomycin in killing S. aureus and MRSA. Moreover, compound 5k could inhibit the bacteria and destroy their membranes in a short time, and showed very low cytotoxicity to NRK-52E cells. Some interesting structure-activity relationships (SARs) were also discussed. These results indicated that these norfloxacin-1,3,4-oxadiazole hybrids could be further developed into new antibacterial agents against MRSA.
- Guo, Yong,Xu, Ting,Bao, Chongnan,Liu, Zhiyan,Fan, Jiangping,Yang, Ruige,Qin, Shangshang
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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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- Synthesis of Thiazolium-Labeled 1,3,4-Oxadiazole Thioethers as Prospective Antimicrobials: In Vitro and in Vivo Bioactivity and Mechanism of Action
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In this study, a type of thiazolium-labeled 1,3,4-oxadiazole thioether bridged by diverse alkyl chain lengths was constructed. The antimicrobial activity of the fabricated thioether toward plant pathogenic bacteria and fungi was then screened. Antibacterial evaluation indicated that title compounds possess specific characteristics that enable them to severely attack three phytopathogens, namely, Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri with minimal EC50 values of 0.10, 3.27, and 3.50 μg/mL, respectively. Three-dimensional quantitative structure-activity relationship models were established to direct the following excogitation for exploring higher active drugs. The in vivo study against plant bacterial diseases further identified the prospective application of title compounds as alternative antibacterial agents. The proteomic technique, scanning electron microscopy patterns, and fluorescence spectrometry were exploited to investigate the antibacterial mechanism. Additionally, some target compounds performed superior inhibitory actions against three tested fungal strains. In view of their simple molecular architecture and highly efficient bioactivity, these substrates could be further explored as promising surrogates for fighting against plant microbial infections.
- Wang, Ming-Wei,Zhu, Huai-He,Wang, Pei-Yi,Zeng, Dan,Wu, Yuan-Yuan,Liu, Li-Wei,Wu, Zhi-Bing,Li, Zhong,Yang, Song
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p. 12696 - 12708
(2019/11/19)
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- 5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma
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Through a phenotypic high-throughput screen using a serum response element luciferase promoter, we identified a novel 5-aryl-1,3,4-oxadiazol-2-ylthiopropionic acid lead inhibitor of Rho/myocardin-related transcription factor (MRTF)/serum response factor (SRF)-mediated gene transcription with good potency (IC50 = 180 nM). We were able to rapidly improve the cellular potency by 5 orders of magnitude guided by sharply defined and synergistic SAR. The remarkable potency and depth of the SAR, as well as the relatively low molecular weight of the series, suggests, but does not prove, that binding to the unknown molecular target may be occurring through a covalent mechanism. The series nevertheless has no observable cytotoxicity up to 100 μM. Ensuing pharmacokinetic optimization resulted in the development of two potent and orally bioavailable anti-fibrotic agents that were capable of dose-dependently reducing connective tissue growth factor gene expression in vitro as well as significantly reducing the development of bleomycin-induced dermal fibrosis in mice in vivo.
- Kahl, Dylan J.,Hutchings, Kim M.,Lisabeth, Erika Mathes,Haak, Andrew J.,Leipprandt, Jeffrey R.,Dexheimer, Thomas,Khanna, Dinesh,Tsou, Pei-Suen,Campbell, Phillip L.,Fox, David A.,Wen, Bo,Sun, Duxin,Bailie, Marc,Neubig, Richard R.,Larsen, Scott D.
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p. 4350 - 4369
(2019/05/08)
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- Synthesis and biological activities of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety
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A series of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety were designed, synthesized and evaluated for their antibacterial, antifungal and antiviral activities. The bioassay results indicated that most of target compounds showed good antiviral activities against tobacco mosaic virus (TMV) and antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (Rs). Especially, the anti-Xoo effect of title compounds 5k (N-(5-methoxybenzo[d]thiazol-2-yl)-2-((5-(2-tolyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) and the anti-Rs effect of title compounds 5a (N-(5-nitrobenzo[d]thiazol-2-yl)-2-((5-(4-(trifluorom ethyl)phenyl)-1,3,4-thiadiazol-2-yl)thio)acetmide) respectively reached 52.4% and 71.6% at 100 μg/mL, which are superior to that of bismerthiazol (32.0% and 52.3%). In addition, the protective and inactivation activities of title compound 5i (N-(5-methoxybenzo [d]thiazol-2-yl)-2-((5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) against TMV were 79.5% and 88.3%, respectively, which are better than that of ningnanmycin (76.4% and 86.8%). The above research showed that benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety may be used as potential molecular templates in searching for highly-efficient antiviral and antibacterial agents.
- Tang, Xu,Wang, Zhongbo,Zhong, Xinmin,Wang, Xiaobin,Chen, Lijuan,He, Ming,Xue, Wei
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p. 241 - 248
(2019/01/04)
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- Novel Molecular Hybrids of N-Benzylpiperidine and 1,3,4-Oxadiazole as Multitargeted Therapeutics to Treat Alzheimer's Disease
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Multitargeted hybrids of N-benzylpiperidine and substituted 5-phenyl-1,3,4-oxadiazoles were designed, synthesized, and evaluated against Alzheimer's disease (AD). Tested compounds exhibited moderate to excellent inhibition against human acetylcholinesterase (hAChE), butyrylcholinesterase (hBChE), and beta-secretase-1 (hBACE-1). The potential leads 6g and 10f exhibited balanced inhibitory profiles against all the targets, with a substantial displacement of propidium iodide from the peripheral anionic site of hAChE. Hybrids 6g and 10f also elicited favorable permeation across the blood-brain barrier and were devoid of neurotoxic liability toward SH-SY5Y neuroblastoma cells. Both leads remarkably disassembled Aβ aggregation in thioflavin T-based self- and AChE-induced experiments. Compounds 6g and 10f ameliorated scopolamine-induced cognitive dysfunctions in the Y-maze test. The ex vivo studies of rat brain homogenates established the reduced AChE levels and antioxidant activity of both compounds. Compound 6g also elicited noteworthy improvement in Aβ-induced cognitive dysfunctions in the Morris water maze test with downregulation in the expression of Aβ and BACE-1 proteins corroborated by Western blot and immunohistochemical analysis. The pharmacokinetic study showed excellent oral absorption characteristics of compound 6g. The in silico molecular docking and dynamics simulation studies of lead compounds affirmed their consensual binding interactions with PAS-AChE and aspartate dyad of BACE-1.
- Sharma, Piyoosh,Tripathi, Avanish,Tripathi, Prabhash Nath,Singh, Saumitra Sen,Singh, Surya Pratap,Shrivastava, Sushant Kumar
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p. 4361 - 4384
(2019/10/16)
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- Design, synthesis, insecticidal activity and 3D-QSR study for novel trifluoromethyl pyridine derivatives containing an 1,3,4-oxadiazole moiety
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A series of trifluoromethyl pyridine derivatives containing 1,3,4-oxadiazole moiety was designed, synthesized and bio-assayed for their insecticidal activity. The result of bio-assays indicated the synthesized compounds exhibited good insecticidal activity against Mythimna separata and Plutella xylostella, most of the title compounds show 100% insecticidal activity at 500 mg L-1 and >80% activity at 250 mg L-1 against the two pests. Compounds E18 and E27 showed LC50 values of 38.5 and 30.8 mg L-1 against Mythimna separata, respectively, which were close to that of avermectin (29.6 mg L-1); compounds E5, E6, E9, E10, E15, E25, E26, and E27 showed 100% activity at 250 mg L-1, which were better than chlorpyrifos (87%). CoMFA and CoMSIA models with good predictability were proposed, which revealed the electron-withdrawing groups with an appropriate bulk at 2- and 4-positions of benzene ring could enhance insecticidal activity.
- Xu,Wang,Luo,Yu,Guo,Fu,Zhao,Wu
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p. 6306 - 6314
(2018/02/19)
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- N-(5-Methyl-1,3-Thiazol-2-yl)-2-{[5-((Un)Substituted- Phenyl)1,3,4-Oxadiazol-2-yl]Sulfanyl}acetamides. Unique Biheterocycles as Promising Therapeutic Agents
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An electrophile, 2-bromo-N-(5-methyl-1,3-thiazol-2-yl)acetamide, was synthesized by the reaction of 5-methyl-1,3-thiazol-2-amine and bromoacetyl bromide in an aqueous medium. In a parallel scheme, a series of (un)substituted benzoic acids was converted sequentially into respective esters, acid hydrazides, and then into 1,3,4-oxadiazole heterocyclic cores. The electrophile was coupled with the aforementioned 1,3,4-oxadiazoles to obtain the targeted bi-heterocyles. Structural analysis of the synthesized compounds was performed by IR, EI-MS, 1H NMR, and 13C NMR. The enzyme inhibition study of these molecules was carried out against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, α-glucosidase, and urease. The interactions of these compounds with respective enzymes were recognized by their in silico study. Moreover, their cytotoxicity was also determined to find out their utility as possible therapeutic agents.
- Abbasi,Ramzan,Aziz-ur-Rehman,Siddiqui,Shah,Hassan,Seo,Ashraf,Mirza,Ismail
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p. 801 - 811
(2019/02/27)
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- Synthesis and Biological Activity of Anthranilic Diamide Derivatives Incorporating 1,3,4-oxadiazole or Nitrogen-containing Saturated Heterocyclic Moieties
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A series of novel anthranilic diamide derivatives incorporating 1,3,4-oxadiazole or nitrogen-containing saturated heterocyclic moieties were synthesized, characterized, and evaluated for bacteriostatic activity against three phytopathogenic bacteria Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), Ralstonia solanacearum (R. solanacearum). The preliminary biological results indicated that most compounds exhibit bacteriostatic activity against three phytopathogenic bacteria. Among these compounds, compounds 6g, 6f, and 6i displayed better antibacterial activity. In the test with concentration of 200 μg/mL, antibacterial activity of compound 6i and 6j was 96%. In particular, the bacteriostatic activity displayed by compound 6h against Xoo is similar to the one displayed by commercial drug bismerthiazol.
- Zhou, Wen-Juan,Zhang, Li,Xiao, Wei,Chen, He-Ju,Wu, Wen-Neng,Ouyang, Gui-Ping
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p. 1423 - 1429
(2017/03/27)
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- Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study
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By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel ‘open-chain’ classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1–23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC50 = 0.15–23.55 μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC50 values of 0.60, 0.15, 0.39 and 0.34 μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide.
- He, Haifeng,Xia, Hongying,Xia, Qin,Ren, Yanliang,He, Hongwu
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p. 5652 - 5661
(2017/10/09)
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- Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives
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Background: Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation. Subsequently, the synthesis of effective chemotherapeutic agents that can induce apoptosis in tumor cell has emerged as a significant approach in cancer drug discovery. Methods: The goal of this work is to develop a potential antitumor agent exerting significant inhibitory effects on cancer cell and low cytotoxicity, for which we focused on the structural features of 1,3,4-oxadiazoles as it a privileged scaffold in modern medicinal chemistry and have the ability to inhibit growth factors, enzymes and kinases potentially involved in the attainment of cellular immortality and carcinogenesis. Result: In vitro MTT screening assay showed the compound 5-aminophenyl-2-butylthio-1,3,4-oxadiazole (5e) showing the highest inhibitory effect against MCF-7 cancer cell with IC50 value 10.05?±?1.08?μM while it is much safer and less toxic on normal cell line (HEK-293). The dose-dependent treatment of MCF-7 cells with 5e resulted in inhibition of cell migration in the wound healing assay. The flow-cytometry analysis showed the cells arrested in G0/G1 phase of the cell cycle. Compound 5e induced apoptosis of MCF-7 cells was characterized using DAPI staining and Annexin V-PE/7-AAD dual binding assay. Reduction of NBT by compound 5e showed a reduced generation of ROS. Western blotting studies showed high activation of apoptotic protein Caspase3 and decrease in expression of anti-apoptotic protein BCL-2. Conclusion: Based on the results of in vitro studies, it could be concluded that compound 5e showed a significant inhibitory growth effect on MCF-7 cells and have the potential to be developed as lead molecule and further structural modifications may result in promising new anticancer agents.
- Khanam, Rashmin,Ahmad, Kamal,Hejazi, Iram I.,Siddique, Ibrar A.,Kumar, Vikash,Bhat, Abdul Roouf,Azam, Amir,Athar, Fareeda
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p. 1027 - 1042
(2017/10/06)
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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 pharmacological screening: Sulfa derivatives of 2-pipecoline-bearing 1,3,4-oxadiazole core
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An electrophile, 1-(4-(bromomethylbenzenesulfonyl)-2-methylpiperidine, was synthesized by the reaction of 2-methylpiperidine (2-pipecoline) and 4-bromomethylbenzenesulfonyl chloride in a weak basic medium under pH control. A series of nucleophiles, 5-aryl/aralkyl-1,3,4-oxadiazol-2-thiols, were synthesized from corresponding carboxylic acids in three steps. The title molecules were synthesized by coupling the electrophile to nucleophiles in an aprotic medium using LiH as an activator. The structures of all synthesized compounds were corroborated through IR, 1H NMR, and EI-MS techniques. All the compounds were screened for their pharmacological behavior, particularly, antibacterial and enzyme inhibitory activities. Notably efficient results were obtained against both gram-positive and gram-negative bacterial strains. Regarding enzyme inhibition, compounds were efficient against acetylcholinesterase and butyrylcholinesterase.
- Aziz-ur-Rehman,Arif,Abbasi,Siddiqui,Rasool,Shah
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p. 328 - 339
(2017/07/04)
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- Rational design, synthesis and biological evaluation of 1,3,4-oxadiazole pyrimidine derivatives as novel pyruvate dehydrogenase complex E1 inhibitors
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On the basis of previous study on 2-methylpyrimidine-4-ylamine derivatives I, further synthetic optimization was done to find potent PDHc-E1 inhibitors with antibacterial activity. Three series of novel pyrimidine derivatives 6, 11 and 14 were designed and synthesized as potential Escherichia coli PDHc-E1 inhibitors by introducing 1,3,4-oxadiazole-thioether, 2,4-disubstituted-1,3-thiazole or 1,2,4-triazol-4-amine-thioether moiety into lead structure I, respectively. Most of 6, 11 and 14 exhibited good inhibitory activity against E. coli PHDc-E1 (IC50 0.97-19.21 μM) and obvious inhibitory activity against cyanobacteria (EC50 0.83-9.86 μM). Their inhibitory activities were much higher than that of lead structure I. 11 showed more potent inhibitory activity against both E. coli PDHc-E1 (IC50 50 50 = 0.97 μM) and cyanobacteria (EC50 = 0.83 μM). The possible interactions of the important residues of PDHc-E1 with title compounds were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that 11d had more potent inhibitory activity than that of 14d or I due to its 1,3,4-oxadiazole moiety with more binding position and stronger interaction with Lsy392 and His106 at active site of E. coli PDHc-E1.
- He, Haifeng,Wang, Wei,Zhou, Yuan,Xia, Qin,Ren, Yanliang,Feng, Jiangtao,Peng, Hao,He, Hongwu,Feng, Lingling
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p. 1879 - 1888
(2016/04/05)
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- Synthesis and antibacterial activity of some new quinaxaline-benzohydrazides
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Quinoxalines have been found to exhibit various biological activities such as antibacterial, antifungal, anti-tubercular, anxiolytic, anticancer, antioxidant, anti-inflammatory, anti-HIV, antihelmintic and anticonvulsant. The present study aims towards synthesis, characterization and determination of antimicrobial susceptibility testing of various novel quinoxaline derivatives. The quinoxaline-benzohydrazides 6a-m have been obtained by the condensation of quinoxaline-2-carboxaldehyde 4 with various benzohydrazides 5a-m in ethanol at reflux temperature. All the newly synthesized quinoxaline-benzohydrazide derivatives have been characterized by 1H NMR, IR and mass spectroscopic analysis. The synthesized quinoxaline-benzohydrazides 6a-m have been screened for antibacterial activity. Most of the compounds show significant antibacterial activity.
- Haripriya,Laxminarayana,Thirumala Chary
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p. 207 - 212
(2017/01/18)
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- Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating Mycobacterium tuberculosis
-
Herein, we report the discovery and structure-activity relationships of 5-substituted-2-[(3,5-dinitrobenzyl)sulfanyl]-1,3,4-oxadiazoles and 1,3,4-thiadiazoles as a new class of antituberculosis agents. The majority of these compounds exhibited outstanding in vitro activity against Mycobacterium tuberculosis CNCTC My 331/88 and six multidrug-resistant clinically isolated strains of M. tuberculosis, with minimum inhibitory concentration values as low as 0.03 μM (0.011-0.026 μg/mL). The investigated compounds had a highly selective antimycobacterial effect because they showed no activity against the other bacteria or fungi tested in this study. Furthermore, the investigated compounds exhibited low in vitro toxicities in four proliferating mammalian cell lines and in isolated primary human hepatocytes. Several in vitro genotoxicity assays indicated that the selected compounds have no mutagenic activity. The oxadiazole and thiadiazole derivatives with the most favorable activity/toxicity profiles also showed potency comparable to that of rifampicin against the nonreplicating streptomycin-starved M. tuberculosis 18b-Lux strain, and therefore, these derivatives, are of particular interest.
- Karabanovich, Galina,Zemanová, Júlia,Smutny, Tomá?,Székely, Rita,?arkan, Michal,Centárová, Ivana,Vocat, Anthony,Pávková, Ivona,?onka, Patrik,Něme?ek, Jan,Stola?íková, Ji?ina,Vejsová, Marcela,Vávrová, Kate?ina,Klime?ová, Věra,Hrabálek, Alexandr,Pávek, Petr,Cole, Stewart T.,Miku?ová, Katarína,Roh, Jaroslav
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supporting information
p. 2362 - 2380
(2016/04/09)
-
- Synthesis and antiviral activity of novel thioether derivatives containing 1,3,4-oxadiazole/thiadiazole and emodin moieties
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A series of novel thioether derivatives containing 1,3,4-oxadiazole/thiadiazole and emodin moieties were designed and synthesized. The structures of the target compounds were confirmed by 1H NMR, 13C NMR, Infrared, and elemental analysis. The results of bioactivity analysis showed that most of the target compounds exhibited moderate to good antiviral activity against tobacco mosaic virus at a concentration of 500 mg/L. Especially, among the title compounds, Y2, Y8, and Y10 possessed appreciable curative activity in vivo, with inhibition rates of 50.51, 52.08, and 54.62%, respectively, which were similar to that of Ningnanmycin (53.40%).
- Dong, Liangrun,Song, Baojing,Wu, Jian,Wu, Zengxue,Zhu, Yunying,Chen, Xuewen,Hu, Deyu
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p. 904 - 907
(2016/07/06)
-
- Synthesis and antibacterial activity of pyridinium-tailored 2,5-substituted-1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives
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By introducing the pyridinium group into 2,5-substituted-1,3,4-oxadiazole, a series of pyridinium-tailored 2,5-substituted-1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives were obtained, and their antibacterial activities were evaluated via turbidimeter test in vitro. The bioassays reveal that most of the target compounds exhibit better inhibition activities against pathogen Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri than positive controls bismerthiazol (CK1) or thiodiazole copper (CK2). Among them, I-8, I-10, I-12, II-10, II-12, III-10, and III-12 exert excellent inhibition activities against the three pathogenic bacteria with the half-maximal effective concentration (EC50) values ranging from 0.54 to 12.14 μg/mL. Our results demonstrate that pyridinium-tailored 1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives can serve as potential alternative bactericides for the management of plant bacterial diseases.
- Wang, Pei-Yi,Zhou, Lei,Zhou, Jian,Wu, Zhi-Bing,Xue, Wei,Song, Bao-An,Yang, Song
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p. 1214 - 1217
(2016/02/23)
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- An efficient nonconventional glycerol-based solid acid catalyzed synthesis and biological evaluation of phosphonate conjugates of 1,2,4-triazole thiones
-
A series of diethyl (3-((5-aryl-1H-1,2,4-triazol-3-yl)thio)propyl)phos-phonates (7a-t) has been synthesized in excellent yields by coupling diethyl (3-bromopropyl)phosphonate and 5-aryl-1H- 1,2,4-triazol-3-thiones employing an efficient, green and nonconventional heterogeneous SO3Hcarbon catalyst derived from glycerol. In addition, a facile and green approach for the esterification of carboxylic acids by utilizing glycerol-based solid acid catalyst has been reported. Structures of the synthesized compounds were characterized by IR, NMR and HRMS studies. These triazole derivatives were screened for their in vitro cytotoxicity using the standard MTT (3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide) assay against a panel of five different human cancer cell lines (HeLa: Cervix, A549: Lung, A375: Skin, MDA-MB-231: Breast and T98G: Brain). The antimicrobial activities of the synthesized compounds were investigated against four bacterial strains: Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and three fungal strains: Aspergillus Niger, Aspergillus terreus, Aspergillus fumigatus. Preliminary results indicate that the compound 7f displayed maximum anticancer activity and the compounds 7d, 7e, 7f, 7m and 7q exhibited moderate antibacterial activity. The compounds 7g, 7h, 7o and 7p showed good antifungal activity with high inhibition zone diameter compared to the standard drug.
- Murty, Madugula S.R.,Katiki, Mohana R.,Rao, Busam R.,Narayanan, Sai S.,Anto, Ruby J.,Buddana, Sudhreer K.,Prakasham, Reddy S.,Devi, Bethala L.A.P.,Prasad, Rachapudi B.N.
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p. 968 - 981
(2016/10/31)
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- Novel hybrid-pyrrole derivatives: Their synthesis, antitubercular evaluation and docking studies
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Using novel hybrid molecules for the treatment of tuberculosis is one of the latest approaches. Keeping this concept in mind, thirty two hybrid compounds were synthesized, with pyrrole as one of the moieties, clubbed to coumarin, ibuprofen and isoniazid. The compounds were evaluated against Mycobacterium tuberculosis H37Rv strain. Compounds 7e and 8e exhibited MIC of 3.7 and 5.10 μg mL-1 and growth inhibition of 95% and 92%, respectively. These compounds were also active against single drug resistant bacterial strains. The compounds were devoid of cytotoxicity when tested against Vero African green monkey kidney cell line. Docking study was carried out on enoyl acyl carrier protein enzyme to provide some understanding into the mechanism of action of these compounds.
- Saha, Rikta,Alam, Md. Mumtaz,Akhter, Mymoona
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p. 12807 - 12820
(2015/02/19)
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- Synthesis and antimicrobial activity of new imidazole-hydrazone derivatives
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Hydrazones demonstrated significant antimicrobial activity, antitubercular activity and antitumoral activity in medicinal areas. The imidazole nucleus is well known to play an important role in living organisms since it is incorporated into the histidine molecule and many other important biological, pharmacological and therapeutic activities. Condensation of 4-phenyl-1H-imidazole-2-carbaldehyde (3) with various selected benzohydrazides (4a-m) resulted in imidazole-hydrazone derivatives (5a-m). They were evaluated for antibacterial and antifungal activity against A. Niger, C. albicans (fungal strains), E. coli and P. aeruginosa (Gram-negative bacteria), S. aureus and S. pyogenes (Gram-positive bacteria) using griseofluvin (for fungi) and ciprofloxacin (for bacteria) as the standard drugs. In general, it is observed that most of the compounds were found to be potent against both the bacterial and fungal strains.
- Prasanna, V. Laxmi,Narender
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p. 3605 - 3608
(2015/12/24)
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- Antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives
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In this study, a series of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt caused by Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum) via the turbidimeter test in vitro. Antibacterial bioassays indicated that most compounds demonstrated appreciable antibacterial bioactivities against Xoo and R. solanacearum. Among the title compounds, compound 4i demonstrated the best inhibitory effect against Xoo and R. solanacearum with half-maximal effective concentration (EC50) values of 14.69 and 15.14 μg/mL, respectively, which were even better than those of commercial agents Bismerthiazol and Thiodiazole Copper. In vivo antibacterial activities tests under greenhouse conditions revealed that the control efficiency of compound 4i against rice bacterial leaf blight and tobacco bacterial wilt were better than those of Bismerthiazol and Thiodiazole Copper. Meanwhile, field trials also indicated that compound 4i demonstrated appreciable control efficiency against rice bacterial leaf blight and tomato bacterial wilt.
- Li, Pei,Shi, Li,Gao, Man-Ni,Yang, Xia,Xue, Wei,Jin, Lin-Hong,Hu, De-Yu,Song, Bao-An
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p. 481 - 484
(2015/02/18)
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- Synthesis, biologicalevaluation, and molecular modeling of (E)-2-aryl-5-styryl-1,3,4-oxadiazolederivatives as acetylcholine esterase inhibitors
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A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a-o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a-q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC50 values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein-ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives. Springer Science+Business Media 2013.
- Kamal, Ahmed,Shaik, Anver Basha,Reddy, G. Narender,Kumar, C. Ganesh,Joseph, Joveeta,Kumar, G. Bharath,Purushotham, Uppula,Sastry, G. Narahari
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p. 2080 - 2092
(2014/05/06)
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- Design, synthesis and molecular modelling studies of novel 3-acetamido-4-methyl benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B
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A novel series of 3-acetamido-4-methyl benzoic acid derivatives designed on the basis of vHTS hit ZINC02765569 were synthesized and screened for PTP1B inhibitory activity. The most potent compounds 3-(1-(5-methoxy-1H-benzo[d] imidazol-2-ylthio)acetamido)-4-methyl benzoic acid (10c, IC50 8.2 μM) and 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)-4-methyl benzoic acid (10e, IC50 8.3 μM) showed maximum PTP1B inhibitory activity. Docking studies were also performed to understand the nature of interactions governing the binding mode of the designed molecules within the active site of the PTP1B enzyme.
- Rakse, Monika,Karthikeyan, Chandrabose,Deora, Girdhar Singh,Moorthy,Rathore, Vandana,Rawat, Arun K.,Srivastava,Trivedi, Piyush
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p. 469 - 476
(2013/11/19)
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- Synthesis, antibacterial activities, and 3d-qsar of sulfone derivatives containing 1, 3, 4-oxadiazole moiety
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A series of sulfone derivatives containing 1, 3, 4-oxadiazole moiety were prepared and evaluated for their antibacterial activities by the turbidimeter test. Most compounds inhibited growth of Ralstonia solanacearum (R. solanacearum) from tomato and tobacco bacterial wilt with high potency, among which compounds 5a and 5b exhibited the most potent inhibition against R. solanacearum from tomato and tobacco bacterial wilts with EC50 values of 19.77 and 8.29 μg/mL, respectively. Our results also demonstrated that 5a, 5b, and a number of other compounds were more potent than commercial bactericides Kocide 3000 and Thiodiazole Copper, which inhibited R. solanacearum from tomato bacterial wilt with EC50 values of 93.59 and 99.80 μg/mL and tobacco bacterial wilt with EC50 values of 45.91 and 216.70 μg/mL, respectively. The structure-activity relationship (SAR) of compounds was studied using three-dimensional quantitative structure-activity relationship (3D-QSAR) models created by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) based on compound bioactivities against tomato and tobacco bacterial wilts. The 3D-QSAR models effectively predicted the correlation between inhibitory activity and steric-electrostatic properties of compounds.
- Li, Pei,Yin, Juan,Xu, Weiming,Wu, Jian,He, Ming,Hu, Deyu,Yang, Song,Song, Baoan
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p. 546 - 556
(2013/11/06)
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- Pharmacological screening for anti-inflammatory, analgesic activity of pyrazolyl derivatives along with molecular docking studies
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The pyrazole derivatives were synthesized and pharmacologically evaluated for analgesic (tail flick) and anti-inflammatory (based on carrageenan-induced paw edema) activities. Compound 4k showed high potency as an anti-inflammatory agent after 3 and 4-h time intervals (P0.001) equipotent to indomethacin. They were devoid of ulcerogenic potential when administered at a dose of 30 mg/kg. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde content (MDA), which is one of the byproduct of lipid peroxidation. Further docking studies of titled compounds was done to understand key interactions responsible for observed inhibition of COX enzyme. The most active compound 4k was found to have -11.192 kcal/mol, as the free energy of binding. Various other key interactions between the synthesized molecules and active site of COX-2 enzyme, responsible for the obtained pharmacological results were also reported. Most of the active compounds were docked well into the active sites of the receptor. Springer Science+Business Media, LLC 2011.
- Kaushik, Darpan,Kumar, Rajnish,Khan, Suroor Ahmed,Chawla, Gita
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p. 3646 - 3655
(2013/02/23)
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- Novel benzofuroxan derivatives against multidrug-resistant Staphylococcus aureus strains: Design using Topliss' decision tree, synthesis and biological assay
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The aim of this study was the design of a set of benzofuroxan derivatives as antimicrobial agents exploring the physicochemical properties of the related substituents. Topliss' decision tree approach was applied to select the substituent groups. Hierarchical cluster analysis was also performed to emphasize natural clusters and patterns. The compounds were obtained using two synthetic approaches for reducing the synthetic steps as well as improving the yield. The minimal inhibitory concentration method was employed to evaluate the activity against multidrug-resistant Staphylococcus aureus strains. The most active compound was 4-nitro-3-(trifluoromethyl)[N′-(benzofuroxan-5-yl) methylene]benzhydrazide (MIC range 12.7-11.4 μg/mL), pointing out that the antimicrobial activity was indeed influenced by the hydrophobic and electron-withdrawing property of the substituent groups 3-CF3 and 4-NO2, respectively.
- Jorge, Salomao Doria,Palace-Berl, Fanny,Masunari, Andrea,Cechinel, Cleber Andre,Ishii, Marina,Pasqualoto, Kerly Fernanda Mesquita,Tavares, Leoberto Costa
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supporting information; experimental part
p. 5031 - 5038
(2011/10/05)
-
- Synthesis of some novel 3,5-disubstituted 1,3,4-oxadiazole derivatives and anticancer activity on EAC animal model
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A series of novel 3,5-disubstituted 1,3,4-oxadiazole- 2-thione derivatives (1e, 2e, 3e, 4e, and 5e) have been synthesized from different substituted aromatic acids. The structure determination of these compounds have been made on the basis of IR, 1H NMR, and Elemental analysis. The effect of all the compounds on tumor growth inhibition was evaluated by studying the parameters-tumor volume, percentage of the tumor cell count (viable and nonviable), hematological values, and the mean survival status of the treated animals on eight groups of Swiss albino mice. Compounds were given at the dose of 50 mg/kg body weight intraperitoneally and all exhibited the significant (P0.001) anticancer activity compared to control. 5-Fluorouracil was used as a standard drug (20 mg/kg body weight i.p.) in the study. All the compounds demonstrated a prominent anticancer activity. The study supported the derivatives of oxadiazoles for the development as potent anticancer molecules. Springer Science+Business Media, LLC 2010.
- Dash, Sasmita,Kumar, B. Ashok,Singh, Jagadish,Maiti,Maity
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experimental part
p. 1206 - 1213
(2012/06/04)
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- N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 2/4-substituted hydrazides: Synthesis and anticonvulsant activity
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A series of N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 2/4-substituted hydrazides were synthesized using appropriate synthetic route and characterized by elemental analysis and spectral data. The anticonvulsant activity of some of the synthesized compounds were evaluated against maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) induced seizure models in mice. The neurotoxicity were assessed using the rotorod method. All the test compounds were administered at doses of 30, 100, and 300 mg/kg body weight and the anticonvulsant activity was noted at 0.5 and 4 h time intervals after the drug administration. Among the compound tested, all except 5g showed protection from seizures in both the animal models. Some titled compounds exhibited lesser CNS depression and neurotoxicity compared to phenytoin. A series of substituted hydrazide derivatives were synthesized, evaluated for their anticonvulsant potency in two animal models along with behavioural and neurotoxicity screen and also subjected to computational parameters.
- Kaushik, Darpan,Khan, Suroor Ahmad,Chawla, Gita,Kumar, Suresh
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experimental part
p. 3943 - 3949
(2010/09/11)
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- Development and assessment of green synthesis of hydrazides
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An expeditious, solvent free one pot method for the preparation of hydrazides from corresponding acids directly under microwave irradiation is developed. The method has been assessed using green chemistry measures and found superior to conventional method with higher E(environmental) factor, atom economy, atom efficiency, carbon efficiency, reaction mass efficiency.
- Saha, Ajoy,Kumar, Rajesh,Kumar, Rajendra,Devakumar
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experimental part
p. 526 - 531
(2010/10/03)
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- Green synthesis of 5-substituted-1,3,4-thiadiazole-2-thiols as new potent nitrification inhibitors [1]
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(Chemical Equation Presented) A fast, efficient synthesis of 5-substituted-1,3,4-thiadiazole-2-thiols was successfully developed, assessed using green chemistry matrices, and compounds were screened for their in vitro nitrification inhibitory activity. The greener method was superior with higher energy efficiency, E(nvironmental) factor, atom economy, atom efficiency, carbon efficiency, and reaction mass efficiency.
- Saha, Ajoy,Kumar, Rajesh,Kumar, Rajendra,Devakumar
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experimental part
p. 838 - 845
(2010/10/04)
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- Novel 4H-1,3,4-oxadiazin-5(6H)-ones with hydrophobic and long alkyl chains: Design, synthesis, and bioactive diversity on inhibition of monoamine oxidase, chitin biosynthesis and tumor cell
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A new series of nitrogen-containing heterocycles 4H-1,3,4-oxadiazin-5(6H)-ones derivatives with hydrophobic and long chains were designed and synthesized by direct cyclization reaction of N′-alkylation substituted aroylhydrazines with chloroacetyl chloride. The preliminary assays showed that some of the compounds displayed moderate to good inhibitory activities toward monoamine oxidase (MAO) at the concentration of 10-5-10-3 M, and antitumor activities against human lung cancer A-549 and human prostate cancer PC-3 cell lines at μM level, which might provide new scaffold for anticancer agents. Furthermore, compounds 5i and 5m exhibited significant inhibitory activity on chitin biosynthesis, which might represent a novel class of highly potential inhibitors of chitin synthesis. Crown Copyright
- Ke, Shao-Yong,Qian, Xu-Hong,Liu, Feng-Yi,Wang, Ni,Yang, Qing,Li, Zhong
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scheme or table
p. 2113 - 2121
(2009/10/02)
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- Diacylhydrazine derivatives as novel potential chitin biosynthesis inhibitors: Design, synthesis, and structure-activity relationship
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A series of diacylhydrazine derivatives containing hydrophobic alkyl chains have been designed and synthesized. The target molecules have been identified on the basis of analytical spectral (IR, 1H NMR, 13C NMR, and HRMS) data. All synthesized compounds have been screened for their potential inhibition in vitro against chitin synthesis using yeast cell extracts. The preliminary assays indicate that some of the compounds display moderate to good inhibitory activity. Structure-activity relationship (SAR) is also discussed based on the experimental data, and the further analysis of the quantitative structure-activity relationship (QSAR) indicates that the electronic parameter is the main factor to affect inhibition activities.
- Ke, Shaoyong,Qian, Xuhong,Liu, Fengyi,Wang, Ni,Fan, Feng,Li, Zhong,Yang, Qing
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experimental part
p. 2985 - 2993
(2009/10/02)
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- Novel lead structures for p38 MAP kinase via FieldScreen virtual screening
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p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-eight diverse compounds were selected for biological analysis, using molecular field similarity to known inhibitors, while explicitly removing any structure that shared a scaffold with previously reported p38 inhibitors. Of these, 11 (19%) showed ≥20% inhibition of p38 at 10 μM. We chose to prepare analogues of two distinct chemical series resulting in a potential lead compound with pIC50 of 6.4. Modeling of SAR using FieldAlign, a ligand alignment protocol, was used to rationalize the SAR of the series of thiadiazole based inhibitors.
- Cheeseright, Timothy J.,Holm, Melanie,Lehmann, Frank,Luik, Sabine,Gottert, Marcia,Melville, James L.,Laufer, Stefan
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scheme or table
p. 4200 - 4209
(2010/01/16)
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- 1,3,4-Oxadiazoline derivatives as novel potential inhibitors targeting chitin biosynthesis: Design, synthesis and biological evaluation
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Two series of 1,3,4-oxadiazoline heterocycle derivatives were designed, synthesized and identified. Bioactivity assays showed that all synthesized compounds inhibited chitin synthesis in yeast, suggesting they might be a novel class of potential inhibitors against chitin biosynthesis. The structure-activity relationships (SAR) of these compounds are discussed.
- Ke, Shaoyong,Liu, Fengyi,Wang, Ni,Yang, Qing,Qian, Xuhong
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scheme or table
p. 332 - 335
(2011/02/26)
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- 1,3,4-Oxadiazole-3(2H)-carboxamide derivatives as potential novel class of monoamine oxidase (MAO) inhibitors: Synthesis, evaluation, and role of urea moiety
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A new series of 1,3,4-oxadiazole-3(2H)-carboxamide derivatives have been synthesized by direct heterocyclization reaction of substituted benzoylisocyanate with various aroylhydrazones as novel monoamine oxidase inhibitors (MAOIs). The target molecules have been identified on the basis of satisfactory analytical and spectra (IR, 1H NMR, 13C NMR, and HR-MS) data. The newly synthesized compounds were evaluated for their MAO inhibitory activity by kynuramine fluorimetric assay method. The preliminary results showed that most of the compounds have moderate inhibitory activities toward MAO at the concentration of 10-5-10-3 M. This work may provide a novel class of lead compounds with potential MAO inhibitions for further optimization.
- Ke, Shaoyong,Li, Zhong,Qian, Xuhong
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p. 7565 - 7572
(2008/12/23)
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- Synthesis and?antimicrobial studies of?a?new series of?2-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}-5-substituted-1,3,4-oxadiazoles
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A series of novel 2-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}-5-substituted-1,3,4-oxadiazoles were synthesized by the oxidative cyclisation of hydrazones derived from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde and aroylhydrazines using chloramine-T as oxidant. IR, NMR and elemental analysis characterized the newly synthesized compounds. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Out of the compounds studied, compounds 8c and 8d showed significant inhibition. Compounds 8b, 8f, 8k and 8e showed moderate activity. The minimum inhibitory concentration of the compounds was in the range of 8-26 μg ml-1 against bacteria and 8-24 μg ml-1 against fungi. The title compounds represent a novel class of potent antimicrobial agents.
- Gaonkar,Rai,Prabhuswamy
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p. 841 - 846
(2007/10/03)
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- Stereoselective synthesis and fungicidal activities of (E)-α- (methoxyimino)-benzeneacetate derivatives containing 1,3,4-oxadiazole ring
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Fifteen novel (E)-α-(methoxyimino)-benzeneacetate derivatives, the analogues of strobilurins, which contain two pharmacophoric substructures of (E)-methyl methoxyiminoacetate moiety and 1,3,4-oxadiazole ring were stereoselectively synthesized. It was first found that the coupling reaction could give stereoselectively the key intermediate (E) and (Z)-methyl 2-(hydroxyimino)-2-o-tolylacetate 2 with a ratio of 14:1. The preliminary bioassays indicated that all the compounds 1 showed potent fungicidal activity against Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Physalospora piricola and Bipolaris mayclis, and all of the tested compounds 1a-1o had more potent fungicidal activities against R. solani than Kresoxim-methyl.
- Li, Yan,Liu, Jie,Zhang, Hongquan,Yang, Xiangping,Liu, Zhaojie
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p. 2278 - 2282
(2007/10/03)
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- Four substituted benzohydrazides: Hydrogen-bonded structures in one, two and three dimensions
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The molecules of 2,6-dichlorobenzohydrazide, C7H 6Cl2N2O, are linked into simple chains by a single N-H...O hydrogen bond, while in the isomeric compound 2,4-dichlorobenzo-hydrazide, the molecules are linked by
- Wardell, Solange M.S.V.,Vasconcelos, Thatyana R. A.,De Souza, Marcus V. N.,Wardell, James L.,Low, John N.,Glidewell, Christopher
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p. o618-o624
(2007/10/03)
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- Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their structure-anti-mycobacterial activities
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The preparation of novel 5-aryl-2-thio-1,3,4-oxadiazoles 4a-41 and the computer-aided study of their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) are reported. The average accuracy of the electronic-topological method and neural network methods applied to the activity prediction in leave-one-out cross validation is 80%.
- Macaev, Fliur,Rusu, Ghenadie,Pogrebnoi, Serghei,Gudima, Alexandru,Stingaci, Eugenia,Vlad, Ludmila,Shvets, Nathaly,Kandemirli, Fatma,Dimoglo, Anatholy,Reynolds, Robert
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p. 4842 - 4850
(2007/10/03)
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- Structural modifications of the primary amino group of anticonvulsant aryl semicarbazones
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A number of aryl semicarbazones had been shown previously to possess significant anticonvulsant properties. The principal objective of the present investigation was to determine the importance of the primary amino group in this series of compounds by replacing it with other substituents. The results indicate that the amino group was not essential for anticonvulsant activity. However its replacement by an aryl ring generally abolished activity while a terminal phenylamino function was better tolerated. Thus both the size of the group and its hydrogen bonding capabilities appear to influence bioactivity. Alteration of the oxygen atom of the semicarbazones by isosteres did not enhance anticonvulsant properties.
- Dimmock,Puthucode,Lo,Quail,Yang,Stables
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