- Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors
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Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2′-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2′-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2′-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 μM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.
- Liu, Mei-Ling,Li, Wei-Yi,Fang, Hai-Lian,Ye, Ya-Xi,Li, Su-Ya,Song, Wan-Qing,Xiao, Zhu-Ping,Ouyang, Hui,Zhu, Hai-Liang
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- New 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: synthesis, in vitro and in silico enzymatic and toxicity evaluations
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Herein, a new series of 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors was designed and synthesized. All the synthesized compounds exhibited excellent inhibition potencies (IC50 values = 55.6–149.2 μM)
- Sepehri, Nima,Azizian, Homa,Ghadimi, Reza,Abedinifar, Fahimeh,Mojtabavi, Somayeh,Faramarzi, Mohammad Ali,Moghadamnia, Ali Akbar,Zabihi, Ebrahim,Mohebbi, Gholamhossein,Larijani, Bagher,Hamedifar, Haleh,Mohammadi-Khanaposhtani, Maryam,Mahdavi, Mohammad
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p. 679 - 693
(2021/06/14)
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- PERIPHERAL ALKYL AND ALKENYL CHAINS EXTENDED BENZENE DERIVATIVES AND PHARMACEUTICAL COMPOSITION INCLUDING THE SAME
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The compounds represented by Formula (I), which are peripheral alkyl and alkenyl chains extended benzene derivatives, are useful as dual autotaxin (ATX) / histone deacetylase (HD AC) inhibitors. These compounds may be included in a pharmaceutical composition along with a pharmaceutically acceptable carrier, and be used in a therapeutically effective amount for prophylaxis or treatment of various diseases and disorders.
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Paragraph 0063; 0388-0391
(2020/10/20)
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- Design and synthesis of novel pyridazine N-aryl acetamides: In-vitro evaluation of α-glucosidase inhibition, docking, and kinetic studies
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We herein applied the four step-synthetic route to prepare the pyridazine core attached to the various N-aryl acetamides. By this approach, a new series of pyridazine-based compounds were synthesized, characterized and evaluated for their activities against α-glucosidase enzyme. In-vitro α-glucosidase assay established that twelve compounds are more potent than acarbose. Compound 7a inhibited α-glucosidase with the IC50 value of 70.1 μM. The most potent compounds showed no cytotoxicity against HDF cell line. Molecular docking and kinetic studies were performed to determine the modes of interaction and inhibition, respectively.
- Faramarzi, Mohammad Ali,Firoozpour, Loghman,Foroumadi, Alireza,Moghimi, Setareh,Mojtabavi, Somayeh,Sadat Ebrahimi, Seyed Esmaeil,Safari, Fatemeh,Salarinejad, Somayeh,Toolabi, Mahsa
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- Synthesis and biological evaluation of N-(substituted phenyl)-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides as antimicrobial, antidepressant, and anticonvulsant agents
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A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtaine
- Shruthi,Poojary, Boja,Kumar, Vasantha,Prathibha,Hussain, Mumtaz Mohammed,Revanasiddappa,Joshi, Himanshu
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p. 223 - 230
(2015/04/14)
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- Design, synthesis and pharmacological evaluation of novel pyrrolizine derivatives as potential anticancer agents
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A new series of novel pyrrolizine derivatives has been synthesized and biologically evaluated as potential anticancer agents. The starting compounds, 6-amino-7-cyano-N-(3,5-disubstitutedphenyl)-2,3-dihydro-1H-pyrrolizine-5- carboxamides 11a-b, were reacte
- Gouda, Ahmed M.,Abdelazeem, Ahmed H.,Arafa, El-Shaimaa A.,Abdellatif, Khaled R.A.
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- Discovery of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4- piperidyl]methyl]-3,5-dichloro-benzamide as a selective T-type calcium channel (Cav3.2) inhibitor
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The T-type calcium channel inhibitor Mibefradil was reported to protect the heart from atrial remodeling, a key process involved in the development of atrial fibrillation and arrhythmias. Mibefradil is not a selective T-type calcium channel inhibitor and also affects the function of different ion channels. Our aim was to develop a selective T-type calcium channel inhibitor to validate the importance of T-type-related pharmacology in atrial fibrillation. Structural optimisation of a previously disclosed hit series focussed on minimising exposure to the central nervous system and improving pharmacokinetic properties, while maintain adequate potency and selectivity. This resulted in the design of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4- piperidyl]methyl]-3,5-dichloro-benzamide, a novel, selective, peripherally restricted chemical probe to verify the role of T-type calcium channel inhibition on atrial fibrillation protection.
- Giordanetto, Fabrizio,W?llberg, Andreas,Knerr, Laurent,Selmi, Nidhal,Ullah, Victoria,Thorstensson, Fredrik,Lindelo, Asa,Karlsson, Staffan,Nikitidis, Grigorios,Llinas, Antonio,Wang, Qing-Dong,Lindqvist, Anders,H?gberg, ?got,Lindhardt, Emma,Astrand, Annika,Duker, G?ran
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p. 119 - 124
(2013/02/25)
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- Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4- dione derivatives for the treatment of inflammatory diseases
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Twenty-two compounds based on thiazolidine-2,4-dione moiety were synthesized and evaluated for the inhibitory potency on the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) activity, and the generation of prostaglandin E2 (PEG2). (Z)-N-(3-Chlorophenyl)-2-(4- ((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acetamide (3I), superior to the commercial anti-inflammatory drug indomethacin, significantly inhibited iNOS activity (IC50 = 8.66 μM), iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE2 production (IC50 = 4.16 and 23.55 μM, respectively) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Docking study revealed that 3I was perfectly docking into the active site of murine iNOS and suppressed the expression of iNOS protein as evidenced by Western blot analysis. At the dose of 50 mg/kg, oral administration of 3I possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.
- Ma, Liang,Xie, Caifeng,Ma, Yinghua,Liu, Juan,Xiang, Mingli,Ye, Xia,Zheng, Hao,Chen, Zhizhi,Xu, Qinyuan,Chen, Tao,Chen, Jinying,Yang, Jincheng,Qiu, Neng,Wang, Guangcheng,Liang, Xiaolin,Peng, Aihua,Yang, Shengyong,Wei, Yuquan,Chen, Lijuan
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supporting information; experimental part
p. 2060 - 2068
(2011/06/17)
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- Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease
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Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.
- Ma, Liang,Li, Shilin,Zheng, Hao,Chen, Jinying,Lin, Lin,Ye, Xia,Chen, Zhizhi,Xu, Qinyuan,Chen, Tao,Yang, Jincheng,Qiu, Neng,Wang, Guangcheng,Peng, Aihua,Ding, Yi,Wei, Yuquan,Chen, Lijuan
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experimental part
p. 2003 - 2010
(2011/06/25)
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- Discovery of N-(1-adamantyl)-2-(4-alkylpiperazin-1-yl)acetamide derivatives as T-type calcium channel (Cav3.2) inhibitors
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Chemical evolution of a HTS-based fragment hit resulted in the identification of N-(1-adamantyl)-2-[4-(2-tetrahydropyran-4-ylethyl)piperazin-1- yl]acetamide, a novel, selective T-type calcium channel (Cav3.2) inhibitor with in vivo antihypertensive effect in rats.
- Giordanetto, Fabrizio,Knerr, Laurent,Selmi, Nidhal,Llins, Antonio,Lindqvist, Anders,Wang, Qing-Dong,Sthlberg, Pernilla,Thorstensson, Fredrik,Ullah, Victoria,Nilsson, Kristina,O'Mahony, Gavin,Hoegberg, Got,Lindhardt, Emma,Strand, Annika,Duker, Goeran
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scheme or table
p. 5557 - 5561
(2011/10/12)
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- Synthesis and antitumor activities of novel 1,4-substituted phthalazine derivatives
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A series of 1,4-substituted phthalazine derivatives were designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. Among them, compounds 7a-7h showed excellent selectivity for MDA-MB-231 cell line with IC50 values from 1nmol/L to 0.92μmol/L. A preliminary SAR study of these derivatives was performed.
- Zhang, Shu Lan,Liu, Ya Jing,Zhao, Yan Fang,Guo, Qiu Ting,Gong, Ping
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scheme or table
p. 1071 - 1074
(2011/10/05)
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- BENZENESULFONAMIDE COMPOUNDS AND THEIR USE AS BLOCKERS OF CALCIUM CHANNELS
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The invention relates to piperidinyl and hexahydroazepinyl compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein R1-R3, Z and q are defined as set forth in the specification. The inve
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Page/Page column 179-180
(2010/11/28)
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- Infrared and Raman spectra of substituted N-(phenyl)-2-chloroacetamides, XYC5-yNHCOCH2Cl (X = H, o/m/p-CH3, Cl or No2 and y = 1, 2 or 3)
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Several substituted N-(phenyl)-2-chloroacetamides of the configuration XyC6H5-yNHCOCH2Cl (where X = H, o/m/p-CH3, Cl or NO2 and y = 1, 2 or 3) have been synthesized, and their infrared and Raman spectra measured in the solid state with the objective of correlating CO and NH frequencies of these substituted phenylchloroacetamides with 35C1 NQR frequencies of the compounds. The study reveals that there is no systematic variation on substitution with either the infrared CO or NH absorption frequencies or the Raman scattered CO or NH frequencies. The effect of substitution in the phenyl ring in terms of either the electron-donating or electron-withdrawing groups could not be generalized. The same trend is observed even with the disubstituted phenyl-2-chloroacetamides, which may be due to the varying crystalline states of the amides on substitution, as the spectra are measured in the solid state. The infrared frequencies of the amides of the configuration XyC 6H5-yNHCOCH3 (where X = H, Cl, NO2 or CH3 and y = 1, 2 or 3) or CH3CONHR (where R = H, CH3, phenyl or substituted phenyl group) and RCONH2 (where R = H, CH3, C2H5, (CH3) 2, C6H5, (C6H5) 2, C6H5CH2, CH2Cl, CH2F, CHF2, CHCl2, CCl3) have also been examined for comparison purpose. The entire data indicate that even the spectra of these compounds do not show regular trends, for the reasons stated above. The correlation of CO and NH absorption frequencies with 35Cl NQR frequencies of the title compounds are also poor.
- Bhat, D. Krishna,Gowda, B. Thimme
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p. 163 - 168
(2007/10/03)
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