148627-63-8Relevant articles and documents
New isoleucine derived dipeptides as antiprotozoal agent: Synthesis, in silico and in vivo studies.
Ekoh, Ogechi C.,Okoro, Uchechukwu C.,Ali, Rafat,Ugwu, David I.,Okafor, Sunday N.,Ezugwu, James A.
, (2021/02/12)
The increasing emergence of malaria drug-resistant parasites and the deficiency in effective chemotherapy for trypanosomiasis represents a huge challenge in infectious disease treatment in tropical regions. As regards to developing effective antiprotozoal agents, ten new ile-gly dipeptide sulphonamide derivatives were synthesized by condensing compound (10) with (8a-j)using peptide coupling reagents. Compounds11b, 11i and 11j were most potent in clearing Trypanosome brucei in mice with 11b showing comparable activity with diminazene aceturate. In the antimalarial study, 11b was the most active compound, even better than the standard. Molecular docking result suggests good interaction between the reported compounds and the target protein. The results of haematological analysis, liver and kidney function tests showed that the compounds had no adverse effect on the blood and organs. Compound 11b stands out amongst the derivatives haven shown better activity in both the antimalarial and antitrypanosomal assay.
Synthesis, molecular docking and antimalarial activity of phenylalanine-glycine dipeptide bearing sulphonamide moiety
Ali, Rafat.,Aronimo, Babatunde. S.,Ezugwu, James. A.,Ibeji, Collins. U.,Okoro, Uchechukwu. C.,Ugwu, David. I.
, (2021/08/10)
Ten novel phenylalanine-glycine dipeptide sulphonamide conjugate were synthesized and characterized using 1HNMR, 13CNMR, FTIR and HRMS spectroscopic techniques. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with standard drugs. The in vivo antimalarial study, hematological study, liver and kidney function test were evaluated on the synthesized compounds. Compounds 7h, 7i and 7j inhibited the parasite by 34.5–60.2% on day 4 of after-treatment exposure. Compound 7j inhibited the multiplication of the parasite by 60.2% on day 4 of after-treatment which was comparable with that of the standard drug with 68.8% inhibition at same day of after-treatment exposure.
Design, synthesis and biological evaluation of novel naturally-inspired multifunctional molecules for the management of Alzheimer's disease
Chittiboyina, Amar G.,Doerksen, Robert J.,Modi, Gyan,Nayak, Prasanta Kumar,Pandey, Amruta,Pandey, Pankaj,Priya, Khushbu,Rai, Geeta,Shankar, Gauri,Singh, Yash Pal,Tej, Gullanki Naga Venkata Charan,Vishwakarma, Swati
, (2020/05/05)
In our overall goal to overcome the limitations associated with natural products for the management of Alzheimer's disease and to develop in-vivo active multifunctional cholinergic inhibitors, we embarked on the development of ferulic acid analogs. A systematic SAR study to improve upon the cholinesterase inhibition of ferulic acid with analogs that also had lower logP was carried out. Enzyme inhibition and kinetic studies identified compound 7a as a lead molecule with preferential acetylcholinesterase inhibition (AChE IC50 = 5.74 ± 0.13 μM; BChE IC50 = 14.05 ± 0.10 μM) compared to the parent molecule ferulic acid (% inhibition of AChE and BChE at 20 μM, 15.19 ± 0.59 and 19.73 ± 0.91, respectively). Molecular docking and dynamics studies revealed that 7a fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Asp74, Trp286, and Tyr337 in AChE and with Tyr128, Trp231, Leu286, Ala328, Phe329, and Tyr341 in BChE. Compound 7a was found to be an efficacious antioxidant in a DPPH assay (IC50 = 57.35 ± 0.27 μM), and it also was able to chelate iron. Data from atomic force microscopy images demonstrated that 7a was able to modulate aggregation of amyloid β1-42. Upon oral administration, 7a exhibited promising in-vivo activity in the scopolamine-induced AD animal model and was able to improve spatial memory in cognitive deficit mice in the Y-maze model. Analog 7a could effectively reverse the increased levels of AChE and BChE in scopolamine-treated animals and exhibited potent ex-vivo antioxidant properties. These findings suggest that 7a can act as a lead molecule for the development of naturally-inspired multifunctional molecules for the management of Alzheimer's and other neurodegenerative disorders.
Substituted carboxamide analogues as a new class of local anesthetic agents: Synthesis and bio-evaluation
Al-Otaibi, Faisal
, p. 649 - 658 (2018/08/03)
A series of N-(2-oxo-2-(phenylamino) ethyl) substituted-4-carboxamide derivatives were synthesized as local anesthetic agents. The structures of carboxamide derivatives were established on the basis of IR, and1H spectral data. All the compounds were subjected to surface local anesthetic activity assay and infiltration local anesthetic activity assay. Among the tested compounds, N-(2-oxo-2-(p-tolylamino) ethyl) piperidine-1-carboxamide (4h) and N-(2-((4-methoxyphenyl) amino)-2-oxoethyl) piperidine-1-carboxamide (4m) were most promising compounds in terms of surface local anaesthetic and infiltration local anaesthetic activity on rats having considerably lower liver toxicity.
Pyreneamide-based dipodal probes for ultra-sensitive and selective detection of 3,5-dinitrosalicylic acid in an aqueous solution
Kumar, Ashwani,Seok Chae, Pil
, p. 400 - 412 (2017/09/02)
Pyrene-appended dipodal probes (probes 1 and 2) with differences in conformational rigidity were synthesized for sensitive detection of 3,5-dinitrosalicylic acid (DNSA) in an aqueous solution. Both dipodal probes had two pyrene units and exhibited quenchi
COMPOUNDS WHICH HAVE A PROTECTIVE ACTIVITY WITH RESPECT TO THE ACTION OF TOXINS AND OF VIRUSES WITH AN INTRACELLULAR MODE OF ACTION
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, (2016/04/19)
The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells.
N-SUBSTITUTED PYRAZOLO [3,4-D] PYRIMIDINE KETONE COMPOUND, AND PREPARATION PROCESS AND USE THEREOF
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Paragraph 0062; 0063; 0064; 0068; 0069; 0070, (2015/09/22)
Disclosed are an N-substituted pyrazolo[3,4-d]pyrimidine ketone compound of formula (I), and a preparation process and use thereof as a phosphodiesterase IX (PDEIX) inhibitor: wherein R′ is selected from isopropyl, cyclopentyl, cyclohexyl, isobutyl, and o
In silico and pharmacological screenings identify novel serine racemase inhibitors
Mori, Hisashi,Wada, Ryogo,Li, Jie,Ishimoto, Tetsuya,Mizuguchi, Mineyuki,Obita, Takayuki,Gouda, Hiroaki,Hirono, Shuichi,Toyooka, Naoki
, p. 3732 - 3735 (2014/09/03)
d-Serine is a coagonist of the N-methyl-d-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.
Synthesis and anticonvulsant activity of some N-(benzoyl)glycinanilide derivatives
Soyer, Zeynep,Akgul, Ozlem,Tarikogullari, Ayse H.,Calis, Unsal
, p. 4708 - 4714 (2013/09/23)
Glycine is a major inhibitory neurotransmitter and recent studies have shown that certain lipophilic glycine derivatives demonstrate anticonvulsant activity in animal epilepsy models. On the other hand, anilide is another fruitful structure for designing potential anticonvulsant agents. Ameltolide, ralitoline and some phthalimide derivatives are the examples of anilide analogs with potent anticonvulsant activity. In this study, two key structural pharmacophores were combined and a series of N-benzoylglycinanilide derivatives were designed. Their anticonvulsant activities evaluated against maximal electroshock (MES) and subcutaneous metrazole seizure tests, whereas their neurotoxicity was examined by rotarod test. The preliminary screening results indicated that majority of the compounds were effective in the MES test. None of the compounds showed neurotoxicity according to the rotarod test at studied doses. The most active compound in the series is N-(2-((4-methoxyphenyl)amino)- 2-oxoethyl)benzamide (compound 8) which bearing 4-methoxy substituent on the N-phenyl ring.
BIARYL-SUBSTITUTED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
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Page/Page column 19, (2008/12/08)
Biaryl-substituted tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions media
