- 1,3,4-oxadiazole n-mannich bases: Synthesis, antimicrobial, and anti-proliferative activities
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The reaction of 5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thione 3 with formalde-hyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temper-ature yielded the corresponding N-Mannich bases 3-arylaminomethyl-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 4a–l or 3-[(4-substituted piperazin-1-yl)methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 5a–d, respectively. The in vitro inhibitory activity of compounds 4a–l and 5a–d was assessed against pathogenic Gram-positive, Gram-negative bacteria, and the yeast-like pathogenic fungus Candida albicans. The piperazinomethyl derivatives 5c and 5d displayed broad-spectrum antibacterial activities the minimal inhibitory concentration (MIC) 0.5–8 μg/mL) and compounds 4j, 4l, 5a, and 5b showed potent activity against the tested Gram-positive bacteria. In addition, the anti-proliferative activity of the compounds was evaluated against prostate cancer (PC3), human colorectal cancer (HCT-116), human hepatocellular carcinoma (HePG-2), human epithe-lioid carcinoma (HeLa), and human breast cancer (MCF7) cell lines. The optimum anti-proliferative activity was attained by compounds 4l, 5a, 5c, and 5d.
- Al-Wahaibi, Lamya H.,Mohamed, Ahmed A. B.,Tawfik, Samar S.,Hassan, Hanan M.,El-Emam, Ali A.
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- Synthesis, molecular docking, antimicrobial evaluation, and DNA cleavage assay of new thiadiazole/oxadiazole ciprofloxacin derivatives
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Abstract: Herein we report the synthesis of new N-4-piperazinyl thiadiazole and oxadiazole ciprofloxacin derivatives and their antibacterial and antimycobacterial activities. Although thiadiazole ciprofloxacin derivatives compound showed broad spectrum antibacterial activity against all the tested strains either Gram-positive or Gram-negative organisms, the oxadiazole derivatives exhibited weaker antibacterial and antimycobacterial activities than thiadiazole derivatives against most of the tested strains compared with the reference ciprofloxacin. Moreover, the antimycobacterial screening revealed that compounds which containing thiadiazole scaffold potently inhibited Mycobacterium smegmatis at MIC of 1.56 and 3.13, respectively, and modestly inhibited the drug-resistant strains. DNA cleavage assay revealed that thiadiazole ciprofloxacin derivatives inhibited supercoil relaxation, albeit to a lesser extent than ciprofloxacin, and it also increased the amount of nicked substrate produced. Graphic abstract: [Figure not available: see fulltext.].
- Mohammed, Hamada H. H.,Abbas, Samar H.,Abdelhafez, El-Shimaa M. N.,Berger, James M.,Mitarai, Satoshi,Arai, Masayoshi,Abuo-Rahma, Gamal El-Din A. A.
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p. 1809 - 1824
(2019/11/05)
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- 1,3,4-oxadiazole/chalcone hybrids: Design, synthesis, and inhibition of leukemia cell growth and EGFR, Src, IL-6 and STAT3 activities
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A new series of 1,3,4-oxadiazole/chalcone hybrids was designed, synthesized, identified with different spectroscopic techniques and biologically evaluated as inhibitors of EGFR, Src, and IL-6. The synthesized compounds showed promising anticancer activity, particularly against leukemia, with 8v being the most potent. The synthesized compounds exhibited strong to moderate cytotoxic activities against K-562, KG-1a, and Jurkat leukemia cell lines in MTT assays. Compound 8v showed the strongest cytotoxic activity with IC50 of 1.95 μM, 2.36 μM and 3.45 μM against K-562, Jurkat and KG-1a leukemia cell lines, respectively. Moreover; the synthesized compounds inhibited EGFR, Src, and IL-6. Compound 8v was most effective at inhibiting EGFR (IC50 = 0.24 μM), Src (IC50 = 0.96 μM), and IL-6 (% of control = 20%). Additionally, most of the compounds decreased STAT3 activation.
- Fathi, Marwa Ali A.,Abd El-Hafeez, Amer Ali,Abdelhamid, Dalia,Abbas, Samar H.,Montano, Monica M.,Abdel-Aziz, Mohamed
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p. 150 - 163
(2018/12/11)
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- Design, Synthesis and Evaluation of Antitubercular Activity of Novel 1,2,4-Triazoles Against MDR Strain of Mycobacterium tuberculosis
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Emergence of various forms of resistant strains of Mycobacterium tuberculosis led to the exploration of drugs with novel mechanism of action. Recently econazole, an azole based antitubercular agent, attracted major attention for targeting mycobacterial cytochrome P450. In the present study, we designed novel 1,2,4-triazole derivatives based on econazole moiety and evaluated them for in vitro antitubercular activity against M. tuberculosis H37Rv and multi-drug resistant (MDR) strains of Mycobacterium.
- Ganesh Kumar,Gautham Shenoy,Kar, Sidhartha Sankar,Shenoy, Vishnu,Bairy, Indira
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p. 907 - 917
(2018/02/07)
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- Design, synthesis, biological evaluation, and 3D-QSAR analysis of podophyllotoxin–dioxazole combination as tubulin targeting anticancer agents
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The advancement of cancer-fighting drugs has never been a simple linear process. Those drug design professionals begin to find inspiration from the nature after failing to find the ideal products by creative drug design and high-throughput screening. To obtain new molecules for inhibiting tubulin, podophyllotoxin was adopted as the leading compound and 1,3,4-oxadiazole was brought in to the C-4 site of podophyllotoxin in this research. A series of seventeen podophyllotoxin-derived esters have been achieved and then evaluated their antitumor activities against four different cancer cell lines: A549, MCF-7, HepG2, and HeLa. Among all the compounds, compound 7c showed the best antiproliferating properties with IC50?=?2.54?±?0.82?μm against MCF-7 cancer cell line. It was obvious that the content of ROS grew significantly in MCF-7 in a way depending on the dosage. The time- and dose-dependent cell cycle assays revealed that compound 7c could apparently block cell cycle in the phase of G2/M along with the upregulation of cyclin A2 and CDK2 protein. According to further studies, confocal microscopy experiment has certified that compound 7c could restrain cancer from growing by blocking the polymerization of microtubule. Meanwhile, compound 7c could be ideally integrated with the colchicine site of tubulin. In future, it would be feasible to selectively design tubulin inhibitors with the help of 3D-QSAR. This means that it is hopeful to develop compound 7c as a potential agent against cancer due to its biological characteristics.
- Wang, Zi-Zhen,Sun, Wen-Xue,Wang, Xue,Zhang, Ya-Han,Qiu, Han-Yue,Qi, Jin-Liang,Pang, Yan-Jun,Lu, Gui-Hua,Wang, Xiao-Ming,Yu, Fu-Gen,Yang, Yong-Hua
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p. 236 - 243
(2017/07/13)
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- Novel 1,3,4-oxadiazole/oxime hybrids: Synthesis, docking studies and investigation of anti-inflammatory, ulcerogenic liability and analgesic activities
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A novel group of 1,3,4-oxadaiazoles, a group known for their anti-inflammatory activity, is hybridized with nitric oxide (NO) releasing group, oxime, for its gastro-protective action and potential synergistic effect. The synthesized hybrids were evaluated for their anti-inflammatory, analgesic, antioxidant and ulcerogenic activities. Most of the tested compounds showed excellent anti-inflammatory activity with compound 8e being more active than indomethacin. They also showed moderate analgesic activity but no antioxidant one. The ability of the synthesized compounds to inhibit COX-1 and COX-2 is studied and the prepared compounds were able to inhibit both COXs non-selectively with IC50s of 0.75–70.50?μM. Docking studies revealed the mode of interaction of the tested compounds into the empty pocket of the isozymes. All of the synthesized compounds interact with COXs active site with energy scores comparable to that of ibuprofen. All compounds showed a safer profile on the stomach tissue integrity compared to conventional NSAIDs. The designed strategy was applied to ibuprofen to introduce ibuprofen/oxadiazole/NO hybrid. The synthesized ibuprofen hybrid is a promising alternative to ibuprofen having similar anti-inflammatory activity but with safer GIT profile.
- Abd-Ellah, Heba S.,Abdel-Aziz, Mohamed,Shoman, Mai E.,Beshr, Eman A.M.,Kaoud, Tamer S.,Ahmed, Al-Shaimaa F.F.
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supporting information
p. 48 - 63
(2016/09/28)
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- Inhibition of tobacco bacterial wilt with sulfone derivatives containing an 1,3,4-oxadiazole moiety
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A series of new sulfone compounds containing the 1,3,4-oxadiazole moiety were designed and synthesized. Their structures were identified by 1H and 13C nuclear magnetic resonance and elemental analyses. Antibacterial bioassays indicated that most compounds exhibited promising in vitro antibacterial bioactivities against tobacco bacterial wilt at 200 μg/mL. The relationship between structure and antibacterial activity was also discussed. Among the title compounds, 5′c, 5′h, 5′i, and 5′j could inhibit mycelia growth of Ralstonia solanacearum in vitro by approximately 50% (EC50) at 39.8, 60.3, 47.9, and 32.1 μg/mL, respectively. Among them, compound 5′j was identified as the most promising candidate due to its stronger effect than that of Kocide 3000 [Cu(OH)2] within the same concentration range. Field trials demonstrated that the control effect of compound 5′j against tobacco bacterial wilt was better than that of the commercial bactericide Saisentong. For the first time, the present work demonstrated that sulfone derivatives containing 1,3,4-oxadiazole can be used to develop potential bactericides for plants.
- Xu, Wei-Ming,Han, Fei-Fei,He, Ming,Hu, De-Yu,He, Jiang,Yang, Song,Song, Bao-An
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p. 1036 - 1041
(2012/06/04)
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- Synthesis, biological evaluation, and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumor agents
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A series of new 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 6o and 6u exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 6o exhibited significant telomerase inhibitory activity (IC 50 = 2.3 ± 0.07 μM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 6o into the active site of telomerase (3DU6) to determine the probable binding model.
- Zheng, Qing-Zhong,Zhang, Xiao-Min,Xu, Ying,Cheng, Kui,Jiao, Qing-Cai,Zhu, Hai-Liang
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scheme or table
p. 7836 - 7841
(2011/01/13)
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