- Oxazole ring-containing honokiol thioether derivative and preparation method and application thereof
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The invention discloses an oxazole ring-containing honokiol thioether derivative, a preparation method thereof and application of the oxazole ring-containing honokiol thioether derivative as an alpha-glucosidase inhibitor, the chemical structure of the oxazole ring-containing honokiol thioether derivative is shown as a general formula (I), and R is selected from non-substituted or substituted phenyl. Compared with the prior art, the invention provides the novel honokiol thioether derivative containing the oxazole ring, and the honokiol thioether derivative containing the oxazole ring has good inhibitory activity on alpha-glucosidase, provides more possibilities for treating diabetes, and is expected to be used for preparing novel candidate drug molecules for treating diabetes. In addition, the preparation process is simple, the cost is low, and the yield is high.
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Paragraph 0042; 0047-0048
(2021/08/11)
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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 and biological evaluation of honokiol derivatives bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3h)-ones as potential viral entry inhibitors against sars-cov-2
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The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 μM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 μM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD’s binding with ACE2. Importantly, 6a and 6p (TC50 > 100 μM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p’s antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.
- Bai, Li-Ping,Guo, Yong,Jiang, Zhi-Hong,Liu, Jia-Zheng,Meng, Jie-Ru,Xu, Ting,Zheng, Zhi-Yuan
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- Discovery of 3,5-dimethylisoxazole derivatives as novel, potent inhibitors for bromodomain and extraterminal domain (BET) family
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Bromodomain and extra-terminal (BET) is a promising therapeutic target for various hematologic cancers. We used the BRD4 inhibitor compound 13 as a lead compound to develop a variety of compounds, and we introduced diverse groups into the position of the compound 13 orienting toward the ZA channel. A series of compounds (14–23, 38–41, 43, 47–49) bearing triazolopyridazine motif exhibited remarkable BRD4 protein inhibitory activities. Among them, compound 39 inhibited BRD4(BD1) protein with an IC50 of 0.003 μM was superior to lead compound 13. Meanwhile, compound 39 possess activity, IC50 = 2.1 μM, in antiproliferation activity against U266 cancer cells. On the other hand, compound 39 could arrest tumor cells into the G0/G1 phase and induce apoptosis, which was consistent with its results in inhibiting cell proliferation. Biological and biochemical data suggest that BRD4 protein might be a therapeutic target and that compound 39 is an excellent lead compound for further development.
- Fang, Lincheng,Hu, Zhaoxue,Yang, Yifei,Chen, Pan,Zhou, Jinpei,Zhang, Huibin
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supporting information
(2021/04/15)
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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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- Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents
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Structural based molecular docking approach revealed the findings of 2-(phenoxymethyl) -5-phenyl-1,3,4-oxadiazole derivatives. The compounds (7a-o) were synthesized and characterized well by using conventional methods. The compounds, 7b and 7m were reconfirmed through single crystal XRD analysis. The synthesized compounds (7a-o) were evaluated their antiproliferative activities against MCF-7 and MDA-MB-453. Furthermore, Lipinski's rule of five and pharmacokinetic properties were predicted for the test compounds. These results demonstrate that the compounds 7b and 7d exhibit more potent cytotoxicity and 7d exhibits dose-dependent activity and reduced cell viability. Further, the mechanism of action for the induced apoptosis was observed through morphological changes and western blotting analysis. These findings may furnish the lead for further development.
- Lakshmithendral,Saravanan,Elancheran,Archana,Manikandan,Arjun,Ramanathan,Lokanath,Kabilan
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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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- Synthesis and antitumor activities of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety
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A series of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety were designed, synthesized and evaluated for their in vitro antitumor activities against SMMC-7721, MCF-7 and A549 human tumor cell lines by CCK-8 assay. The bioassay results demonstrated that most of the tested compounds showed potent antitumor activities, and some compounds exhibited stronger effects than positive control 5-fluorouracil (5-FU) against various cell lines. Among these compounds, compound 8d showed the best inhibitory effect against SMMC-7721 cells, with IC50 value of 2.84 μM. Compounds 8k and 8n displayed highly effective antitumor activities against MCF-7 cells, with IC50 values of 4.56 and 4.25 μM, respectively. Compounds 8a and 8n exhibited significant antiproliferative activity against A549 cells, with IC50 values of 4.11 and 4.13 μM, respectively. The pharmacological results suggest that the substituents of phenyl ring on the 1,3,4-oxadiazole are vital for modulating antiproliferative activities against various tumor cell lines.
- Zhang, Kai,Wang, Peng,Xuan, Li-Na,Fu, Xiao-Yun,Jing, Fen,Li, Sha,Liu, Yu-Ming,Chen, Bao-Quan
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supporting information
p. 5154 - 5156
(2014/12/11)
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- Synthesis and antimicrobial properties of 1,3,4-oxadiazole analogs containing dibenzosuberane moiety
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A series of ten novel 1,3,4-oxadiazole analogs containing dibenzosuberane moiety were synthesized using linear as well as convergent synthesis approach. All the compounds were characterized by mass spectrometry, infrared (IR), 1H and 13C nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopies and elemental analysis. These compounds were evaluated for antibacterial and antifungal activities. Among ten analogs, four compounds, namely, 8a, 8d, 8e and 8j were found to be highly active antibacterial and antifungal agents.
- Moger, Manjunath,Satam, Vijay,Govindaraju, Darshan Raj C.,Paniraj,Gopinath, Vadiraj S.,Hindupur, Rama Mohan,Pati, Hari N.
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p. 104 - 111
(2014/02/14)
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- Synthesis and structure-activity relationships of antitubercular 2-nitroimidazooxazines bearing heterocyclic side chains
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Recently described biphenyl analogues of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying potent new candidates with improved aqueous solubility. The compounds were constructed by coupling the chiral 2-nitroimidazooxazine alcohol with various halomethyl-substituted arylheterocycles, by cycloadditions to a propargyl ether derivative of this alcohol, or by Suzuki couplings on haloheterocyclic methyl ether derivatives. The arylheterocyclic compounds were all more hydrophilic than their corresponding biphenyl analogues, and several showed solubility improvements. 1-Methylpyrazole, 1,3-linked-pyrazole, 2,4-linked-triazole, and tetrazole analogues had 3- to 7-fold higher MIC potencies against replicating M. tb than predicted by their lipophilicities. Two pyrazole analogues were >10-fold more efficacious than the parent drug in a mouse model of acute M. tb infection, and one displayed a 2-fold higher solubility. 2009 American Chemical Society.
- Sutherland, Hamish S.,Blaser, Adrian,Kmentova, Iveta,Franzblau, Scott G.,Wan, Baojie,Wang, Yuehong,Ma, Zhenkun,Palmer, Brian D.,Denny, William A.,Thompson, Andrew M.
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experimental part
p. 855 - 866
(2010/06/15)
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- Microwave-assisted one-step synthesis of substituted 2-chloromethyl-1,3,4- oxadiazoles
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We have developed a simple one-step synthesis of 2-chloromethyl-1,3,4- oxadiazoles from commercially available acylhydrazides using 1-chloro-2,2,2-trimethoxyethane as a solvent under microwave irradiation.
- Natero, Reina,Koltun, Dmitry O.,Zablocki, Jeffery A.
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p. 2523 - 2529
(2007/10/03)
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- Synthesis and antifeedant activity of new oxadiazolyl 3(2H)-pyridazinones
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A total of 20 new compounds containing the oxadiazolyl 3(2H)-pyridazinone moiety were synthesized. The structures of all the compounds were confirmed by 1H NMR, IR, MS, and elemental analysis. Their insect antifeedant activities against Asiatic corn borer Ostrinia furnacalis (Guenee) were examined and compared with commercial azadirachtin. The compounds exhibited significant levels of activity. The feeding deterrency values of IIIa,j were 57% and 51% at 500 mg/kg concentration, respectively.
- Cao, Song,Qian, Xuhong,Song, Gonghua,Chai, Bing,Jiang, Zhisheng
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p. 152 - 155
(2007/10/03)
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- Synthesis and insecticidal activity of neonicotinoids derivatives
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A new class of compounds- neonicotinoids containing oxadiazole -were synthesized and characterized by using 1H NMR, IR, MS and Elemental Analysis. Their insecticidal activities were tested against Mythimna separata Walker and Aphis rumicis Linnaeus, some of them showed some insecticidal activity.
- Chai, Bing,Cao, Song,Liu, Haidong,Song, Gonghua,Qian, Xuhong
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p. 601 - 606
(2007/10/03)
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- Syntheses and insecticidal activity of new 2-(5-(trifluoromethyl)pyridyloxymethyl)-1,3,4-oxadiazoles
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Eight 2-(5-(trifluoromethyl)pyridyloxymethyl)-1,3,4-oxadiazoles have been designed and synthesized by four-step synthetic route. The structures of all new compounds were confirmed by 1H NMR, mass and HR mass spectroscopy. The preliminary bioass
- Cao, Song,Qian, Xuhong,Song, Gonghua,Huang, Qingchun
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