588680-00-6Relevant articles and documents
Computational study and synthesis of a new class of anticonvulsants with 6 Hz psychomotor seizure test activity: 2-(1,3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides
Kumar, Praveen,Tripathi, Laxmi
, p. 1175 - 1193 (2021/12/21)
Background: About 50 million epileptic cases worldwide and 12 million in India are re-ported. Currently, available drugs yield adequate control of seizure in 60-70% of patients and show many toxic effects. These actualities provoked the search for novel, more efficacious and safer anti-convulsants. Objective: The concatenation of 2-(1,3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides SA 1-10 was designed by molecular hybridization, optimized by computational study and synthesized with the objective of obtaining a prototype of potent anticonvulsant molecules especially active against partial seizures. Methods: Computational study was performed to calculate the pharmacophoric design, projection of the pharmacokinetic parameters and docking scores of the titled compounds with molecular targets of epilepsy. The anticonvulsant activity was ascertained by 6 Hz psychomotor seizure test. Minimal motor impairment showing neurotoxicity was assessed using the Rotarod test. Results: Titled compounds possessed the indispensable elements of pharmacophore and displayed good binding affinity with molecular targets of epilepsy, such as GABA (A) alpha-1 & delta receptor, glutamate receptor, Na+/H+ exchanger and GABA-aminotransferase in docking studies. The most potent compound of the concatenation was 2-(1,3-benzodioxol-5-yloxy)-N'-[4-(4-chlorophenoxy)benzylidene]-acetohydrazide SA 4, showing 100% protection at four different time points with ED50 value 146.8 mg/kg at a TPE of 1 h in mice. Conclusion: The protection shown in 6 Hz test is implicated as the compound's ability to control partial seizures. Thus, the titled compounds can be considered as potential prototype candidates for antiepileptic therapy against partial seizures.
Synthesis, Anticonvulsant Evaluation and Molecular Docking Studies of Novel Benzo[1,3]dioxol-5-yloxy-N′-(4-substituted benzylidene)acetohydrazide Derivatives
Singh, Shailesh Kumar,Tripathi, Laxmi
, p. 199 - 204 (2019/12/02)
Novel (benzo[1,3]dioxol-5-yloxy)-N′-(4-substituted benzylidene)acetohydrazide derivatives were synthesized and their anticonvulsant activity evaluated by MES and scMET seizure models. Compound 2-(benzo[d][1,3]dioxol-5-yloxy)-N′-benzylideneacetohydrazide (
Identification of a Novel Oxadiazole Inhibitor of Mammalian Target of Rapamycin
Lim, Sunwoo,Lee, Hyomin,Kim, Euijung,Hur, Wooyoung
, p. 296 - 303 (2020/02/04)
We performed a biochemical screen against mTOR using in-house small molecule library. Two novel, structurally distinct hits were identified. Among them, a novel oxadiazole scaffold compound (2) suppressed the phosphorylation of both S6K1 and Akt1 in HeLa cells. Docking study suggested that 2 is ATP-competitive and shows a pi-pi interaction with Trp2239 and hydrogen bonds with Trp2239 and Thr2245. Through derivatization, a slightly more potent analogue (2a) was identified with IC50 of 9.6 μM. Our study provides a starting point for discovery of novel potent mTOR inhibitors.
Design and synthesis of 3,4-methylenedioxy-6-nitrophenoxyacetylhydrazone derivatives obtained from natural safrole: New lead-agents with analgesic and antipyretic properties
Bezerra-Netto, Heleno J.C.,Lacerda, Daniel I.,Miranda, Ana Luisa P.,Alves, Helio M.,Barreiro, Eliezer J.,Fraga, Carlos A.M.
, p. 7924 - 7935 (2007/10/03)
In this work, we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and antipyretic properties of new 2-(6-nitro-benzo[1,3]dioxol-5-yloxy)-acetylhydrazone derivatives (3), designed exploring molecular hybridization and isosteric replacement approaches between nimesulide (1) and carbanalogue NAH series (2) developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (4) as starting material. The evaluation of the antinociceptive properties of this series led us to discover a new potent prototype of analgesic and antipyretic agent, that is, NAH derivative 3c, named LASSBio-891, which showed to be more potent than dipyrone used as standard.
