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2‐Hydrazinyl‐N‐(4‐sulfamoylphenyl)acetamide 3 was the key intermediate for the synthesis of novel hydrazones 4–10 and pyrazole derivatives 11–17 . All compounds were tested for their in vivo anti‐inflammatory activity and their ability to inhibit the production of PGE2 in serum samples of rats. IC50 values for the most active compounds for inhibition of COX‐1 and COX‐2 enzymes were determined in vitro, and they were also tested for their ulcerogenic effect. Molecular docking was performed on the active site of COX‐2 to predict their mode of binding to the amino acids. Most of the synthesized compounds showed good anti‐inflammatory activity especially compounds 3, 4, 8, 9, 15, and 17 which showed better activity than diclofenac as the reference drug. Compounds 3, 8, 9, 13, and 15–17 were less ulcerogenic than indomethacine as the reference drug. Most of the synthesized compounds interacted with Tyr 385 and Ser 530 in molecular docking study with additional hydrogen bond for compound 17 . Compound 17 showed good selectivity index value of 11.1 for COX‐1/COX‐2 inhibition in vitro. 相似文献
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Synthesis and Biological Evaluation of New Phthalazinone Derivatives as Anti‐Inflammatory and Anti‐Proliferative Agents
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Alhamzah Dh. Hameed Syed Ovais Raed Yaseen Pooja Rathore Mohammed Samim Surender Singh Kalicharan Sharma Mymona Akhtar Kalim Javed 《Archiv der Pharmazie》2016,349(2):150-159
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Design,Synthesis, and Biological Evaluation of Novel Quinazoline Derivatives as Anti‐inflammatory Agents against Lipopolysaccharide‐induced Acute Lung Injury in Rats
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Lili Dong Zhe Wang Lingfeng Chen Dandan Liang Dengjian Shi Xiaoou Shan Guang Liang 《Chemical biology & drug design》2015,85(6):672-684
Quinazoline has been reported to exhibit multiple bioactivities. The aim of this study was to discover new quinazoline derivatives with preventive effect on lipopolysaccharide‐induced acute lung injury via anti‐inflammatory actions. Thirty‐three 4‐amino quinazolin derivatives were synthesized and screened for anti‐inflammatory activities in lipopolysaccharide‐induced macrophages. The most potent four compounds, 6h, 6m, 6p , and 6q , were shown dose‐dependent inhibition against lipopolysaccharide‐induced TNF‐α and IL‐6 release. Then, the preliminary structure–activity relationship and quantitative structure–activity relationship analyses were conducted. To further determine the effects of quinazolines on acute lung injury treatment, lipopolysaccharide‐induced acute lung injury model was employed. Male Sprague Dawley rats were pretreated with 6m or 6q before instillation of lipopolysaccharide. The results showed that 6m and 6q, especially 6q , obviously alleviated lung histopathological changes, inflammatory cells infiltration, and cytokines mRNA expression initiated by lipopolysaccharide. Taken together, this work suggests that 6m and 6q suppressed the lipopolysaccharide‐induced acute lung injury through inhibition of the inflammatory response in vivo and in vitro, indicating that quinazolines might serve as potential agents for the treatment of acute lung injury and deserve the continuing drug development and research. 相似文献
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Shafiya Yaseen Syed Ovais Rafia Bashir Pooja Rathore Mohammed Samim Surender Singh Vinod Nair Kalim Javed 《Archiv der Pharmazie》2013,346(6):491-498
Nine 4‐arylphthalazones bearing benzenesulfonamide (2a – i ) were synthesized by the condensation of the appropriate 2‐aroylbenzoic acid ( 1a – i ) and 4‐hydrazinobenzenesulfonamide in ethanol. The structures of these compounds were elucidated by elemental analysis, IR, 1H NMR, 13C NMR, and MS spectroscopy. Two compounds, 2b and 2i , showed significant anti‐inflammatory activity comparable to that of the standard drug celecoxib in the carrageenan‐induced rat paw edema model. These compounds ( 2b and 2i ) had selective inhibitory activity towards the COX‐2 enzyme. Compound 2b had a better selectivity ratio (COX‐1/COX‐2) compared to that of celecoxib and can be used as a novel template for the design of selective COX‐2 inhibitors. Compounds 2d and 2i were screened for their antiproliferative activity toward 60 human cancer cell lines by the National Cancer Institute (USA). The compounds 2d and 2i displayed mild activity toward the renal cancer cell line UO‐31. 相似文献
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A novel series of pazopanib derivatives were designed, synthesized, and evaluated for their inhibitory activity against a series of kinases including VEGFR‐2, EGFR, AKT1, ALK1, and ABL1. The anti‐angiogenic activities ex vivo of some compounds were also investigated. Compounds P2d and P2e demonstrated outstanding inhibitory activity against VEGFR‐2 and ABL1 and higher anti‐angiogenic activity compared with Pazopanib, the reference standard. These two compounds ( P2d and P2e ) could be used as novel lead compounds for further development of anticancer agents. 相似文献
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Bo Jiang Yi Zeng Meng‐Jie Li Jin‐Yi Xu Yong‐Na Zhang Qiu‐Juan Wang Ni‐Yue Sun Tao Lu Xiao‐Ming Wu 《Archiv der Pharmazie》2010,343(9):500-508
A series of 1,5‐diaryl‐1,2,4‐triazole derivatives were synthesized and evaluated as cyclooxygenase‐2 (COX‐2) inhibitors. The results of the preliminary biological assays in vivo showed that eight compounds 5b , 6b , 6c , 7c , 8b , 8d , 9c , and 9d have potent anti‐inflammatory activity (P < 0.01), while compounds 6b , 6c , and 9c exhibit marked potency. Compound 6c was then selected for further investigation. In the COX inhibition assay in vitro, compound 6c was identified as a potent and selective inhibitor of COX‐2 (COX‐2 IC50 = 0.37 µM; SI = 0.018), being equipotent to celecoxib (COX‐2 IC50 = 0.26 µM; SI = 0.015). In a rat carrageenan‐induced paw edema assay, 6c exhibited moderate anti‐inflammatory activity (35% inhibition of inflammation) at 2 h after administration of 15 mg/kg as an oral dose. A docking study also revealed that compound 6c binds in the active site of COX‐2 in a similar mode to that of the known selective COX‐2 inhibitor SC‐558. 相似文献
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Pritam N. Dube Shweta S. Bule Santosh N. Mokale Manoj R. Kumbhare Pravin R. Dighe Yogesh V. Ushir 《Chemical biology & drug design》2014,84(4):409-419
The present study reported the synthesis and biologic evaluation of new pyrazolone derivatives for COX‐2 inhibitory activities and investigated in vivo for their anti‐inflammatory activities using carrageenan‐induced rat paw edema model as well as in vitro using HRBC membrane stabilization and protein denaturation method. Eight derivatives showed pronounced COX‐2 inhibition, and 5a, 5d, and 5f exhibited the highest COX‐2 inhibition. The derivatives were further evaluated for antioxidant activity wherein 5a and 5b showed potent free radical‐scavenging activity against DPPH, nitric oxide, and hydrogen peroxide radicals. Molecular docking study revealed the binding orientations of pyrazolone derivatives into the active sites of COX‐2 and thereby helps to design the potent inhibitors. 相似文献
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Zhao‐Hui Wang Tao Wang Shi‐Ning Yao Jing‐cai Chen Wei‐Yi Hua Qi‐Zheng Yao 《Archiv der Pharmazie》2010,343(3):160-166
A series of novel 7‐azaisoindigo derivatives 3–14 were designed, synthesized, and structurally characterized by IR, 1H‐NMR, 13C‐NMR, mass spectra, and elemental analyses. Their antiproliferative activities were evaluated in a hormone‐independent prostate cancer cell line DU145. Among them, compounds 8 , 9 , 14 showed the highest activities. Our study also showed that compounds 7 , 11 , 12 exhibited higher inhibitory activities on CDK2/cyclin A than that of the positive control meisoindigo. Western blot analysis on DU145 cells treated with compounds 7 and 9 demonstrated that 7‐azaisoindigo derivatives could decrease the level of CDK2 activity (phosphorylation) and the expression of cyclin D1, and increase the expression of endogenous cyclin‐dependent inhibitor p27. 相似文献
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Synthesis,Biological Evaluation,and Docking Studies of New 2‐Furylbenzimidazoles as Anti‐Angiogenic Agents: Part II
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Ahmed Temirak Yasser M. Shaker Fatma A. F. Ragab Mamdouh M. Ali Salwa M. Soliman Jeremie Mortier Gerhard Wolber Hamed I. Ali Hoda I. El Diwani 《Archiv der Pharmazie》2014,347(4):291-304
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Synthesis and Evaluation of 3‐(furo[2,3‐b]pyridin‐3‐yl)‐4‐(1H‐indol‐3‐yl)‐maleimides as Novel GSK‐3β Inhibitors and Anti‐Ischemic Agents
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Qing Ye Qiu Li Yubo Zhou Lei Xu Weili Mao Yuanxue Gao Chenhui Li Yuan Xu Yazhou Xu Hong Liao Luyong Zhang Jianrong Gao Jia Li Tao Pang 《Chemical biology & drug design》2015,86(4):746-752
A series of novel 3‐(furo[2,3‐b]pyridin‐3‐yl)‐4‐(1H‐indol‐3‐yl)‐maleimides were designed, synthesized, and biologically evaluated for their GSK‐3β inhibitory activities. Most compounds showed favorable inhibitory activities against GSK‐3β protein. Among them, compounds 5n , 5o , and 5p significantly reduced GSK‐3β substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK‐3β activity. In the in vitro neuronal injury models, compounds 5n , 5o , and 5p prevented neuronal death against glutamate, oxygen–glucose deprivation, and nutrient serum deprivation which are closely associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 5o reduced infarct size by 10% and improved the neurological deficit. The results may provide new insights into the development of novel GSK‐3β inhibitors with potential neuroprotective activity against brain ischemic stroke. 相似文献
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V. Alagarsamy V. Raja Solomon R. V. Sheorey R. Jayakumar 《Chemical biology & drug design》2009,73(4):471-479
A new series of 3‐(3‐ethylphenyl)‐2‐substituted hydrazino‐3H‐quinazolin‐4‐ones were synthesized by reacting the amino group of 2‐hydrazino‐3‐(3‐ethylphenyl)‐3H‐quinazolin‐4‐one with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti‐inflammatory and ulcerogenic index behavior. The compound 2‐(N′‐3‐pentylidene‐hydrazino)‐3‐(3‐ethylphenyl)‐3H‐quinazolin‐4‐one ( AS2 ) emerged as the most active compound in exhibiting analgesic activity and the compound 2‐(N′‐2‐pentylidene‐hydrazino)‐3‐(3‐ethylphenyl)‐3H‐quinazolin‐4‐one ( AS3 ) emerged as the most active compound in exhibiting anti‐inflammatory activity; and these compounds are moderately potent when compared with the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared with aspirin. 相似文献
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Design,Synthesis, and Biological Evaluation of 1,4‐dihydropyridine Derivatives as Potent Antitubercular Agents
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Nisheeth C. Desai Amit R. Trivedi Hardik C. Somani Kandarp A. Bhatt 《Chemical biology & drug design》2015,86(3):370-377
A series of novel 1,4‐dihydropyridine‐3,5‐dicarbamoyl derivatives bearing an imidazole nucleus at C‐4 position were synthesized in excellent yields via multicomponent Hantzsch reaction. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectroscopy. The synthesized compounds 3a‐p were screened for antitubercular activity. Among all the screened compounds, compounds 3j and 3m showed most prominent activity against Mycobacterium tuberculosis with minimum inhibitory concentration of 0.02 μg/mL and SI > 500, making it more potent than first‐line antitubercular drug isoniazid. In addition, these compounds displayed relatively low cytotoxicity. 相似文献
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Synthesis and Cytotoxic Evaluation of Monocarbonyl Analogs of Curcumin as Potential Anti‐Tumor Agents
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Preclinical Research |