18331-71-0Relevant articles and documents
Insights into structure-activity relationships of 3-arylhydrazonoindolin-2-one derivatives for their multitarget activity on β-amyloid aggregation and neurotoxicity
Purgatorio, Rosa,De Candia, Modesto,De Palma, Annalisa,De Santis, Francesco,Pisani, Leonardo,Campagna, Francesco,Cellamare, Saverio,Altomare, Cosimo Damiano,Catto, Marco
, (2018/07/13)
Despite the controversial outcomes of clinical trials executed so far, the prevention of β-amyloid (Aβ) deposition and neurotoxicity by small molecule inhibitors of Aβ aggregation remains a target intensively pursued in the search of effective drugs for treating Alzheimer’s disease (AD) and related neurodegeneration syndromes. As a continuation of previous studies, a series of new 3-(2-arylhydrazono)indolin-2-one derivatives was synthesized and assayed, investigating the effects of substitutions on both the indole core and arylhydrazone moiety. Compared with the reference compound 1, we disclosed equipotent derivatives bearing alkyl substituents at the indole nitrogen, and fairly tolerated bioisosteric replacements at the arylhydrazone moiety. For most of the investigated compounds, the inhibition of Aβ40 aggregation (expressed as pIC50) was found to be correlated with lipophilicity, as assessed by a reversed-phase HPLC method, through a bilinear relationship. The N1-cyclopropyl derivative 28 was tested in cell-based assays of Aβ42 oligomer toxicity and oxidative stress induced by hydrogen peroxide, showing significant cytoprotective effects. This study confirmed the versatility of isatin in preparing multitarget small molecules affecting different biochemical pathways involved in AD.
Palladium(II)/N-Heterocyclic Carbene Catalyzed One-Pot Sequential α-Arylation/Alkylation: Access to 3,3-Disubstituted Oxindoles
Reddy Panyam, Pradeep Kumar,Ugale, Bharat,Gandhi, Thirumanavelan
, p. 7622 - 7632 (2018/06/22)
Rationally designed fluorene-based mono- and bimetallic Pd-PEPPSI complexes were synthesized and demonstrated to be effective for the one-pot sequential α-arylation/alkylation of oxindoles. This streamlined approach offers efficient access to functionalized 3,3-disubstituted oxindoles in excellent yields (up to 89%) under mild reaction conditions.
Design, synthesis, and biological evaluation of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives as anti-proliferative agents through ROS-induced cell apoptosis
Song, Zhuang,Chen, Cai-Ping,Liu, Jun,Wen, Xiaoan,Sun, Hongbin,Yuan, Haoliang
, p. 809 - 819 (2016/09/23)
A novel class of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives were designed and synthesized as potent anti-proliferative agents. Most of these compounds showed potent anti-proliferative activity against some tumor cell lines, including SK-BR-3, MDA-MB-231, HCT-116, SW480, Ovcar-3, HL-60, Saos-2 and HepG2. Compounds 8c and 11h were identified as the most potent ones, while HL-60, HCT116 and MDA-MB-231 were the most sensitive cell lines. Mechanistic study revealed that compound 8c enhanced reactive oxygen species level by inhibiting TrxR and then induced apoptosis by activating apoptosis proteins, bax and cleaved-caspase 3 in HCT116?cells. Preliminary SAR analysis indicated that modifications of the double bond and ester group made great effects on the anti-proliferative activity. Our findings suggested that it was worth further studies on the antitumor potency of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetates.
