153407-40-0Relevant academic research and scientific papers
Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin
Bassetto, Marcella,Brancale, Andrea,Pasqualetto, Gaia,Pileggi, Elisa,Rozanowska, Malgorzata,Schepelmann, Martin,Varricchio, Carmine
supporting information, (2021/09/24)
Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.
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.
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.
Synthesis and structure-activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores
Ho, Bin,Michael Crider,Stables, James P
, p. 265 - 286 (2007/10/03)
Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(α-methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the α-methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg-1, TD50 = 36.4 mg kg-1, PI = 6.3). Replacement of the piperidine ring of 1 by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man.
