7501-05-5Relevant articles and documents
Oxoisoaporphine alkaloid derivatives: Synthesis, DNA binding affinity and cytotoxicity
Tang, Huang,Wang, Xiao-Dong,Wei, Yong-Biao,Huang, Shi-Liang,Huang, Zhi-Shu,Tan, Jia-Heng,An, Lin-Kun,Wu, Jian-Yong,Sun-Chi Chan, Albert,Gu, Lian-Quan
, p. 973 - 980 (2008)
A series of novel oxoisoaporphine alkaloid derivatives, 9-aminoalkanamido-1-azabenzanthrone (general formula Ar-NHCO(CH2)nNR2, Ar = 1-azabenzanthrone, n = 1, 2 or 3), had been synthesized. Compared with 1-azabenzanthrone, the derivatives had significantly higher DNA binding affinity with calf thymus DNA, and higher potent cytotoxicity against different tumor cell lines. The cytotoxicity and the structure-activity relationship of the prepared compounds were studied. The derivatives with two methylene groups (n = 2), and piperidine or ethanolamine functional group in the side chain exhibited highest DNA binding affinity and cytotoxicity.
An Oxidation Study of Phthalimide-Derived Hydroxylactams
Adjei, Bernard L.,Luzzio, Frederick A.
, (2022/01/24)
A systematic study of the oxidation of 3-hydroxy-2-substituted isoindolin-1-ones (hy-droxylactams) and their conversion to the corresponding phthalimides was undertaken using three oxidants. Of special interest was the introduction of nickel peroxide (NiO2 ) as an oxidation system for hydroxylactams and comparison of its performance with the commonly used pyridinium chlorochromate (PCC) and iodoxybenzoic acid (IBX) reagents. Using a range of hydroxylactams, optimal conversions of these substrates to the corresponding imides was achieved with 50 equivalents of freshly prepared NiO2 in refluxing toluene over 5–32 h reaction times. By comparison, oxidations of the same substrates using PCC/silica gel (three equivalents) and IBX (three equivalents) required oxidation times of 1–3 h for full conversion but required lengthier purification. While nominal amounts (~25 mg) of substrate hydroxylactams were used to ascertain conversion, scale-up procedures using all three methods gave good to excellent isolated yields of imides.
4-Hydroxyl-oxoisoaporphine, one small molecule as theranostic agent for simultaneous fluorescence imaging and photodynamic therapy as type II photosensitizer
Xu, Qi,Ji, Yunfan,Chen, Meijun,Shao, Xusheng
, p. 501 - 512 (2021/03/24)
Oxoisoaporphine (OA) is a plant phototoxin isolated from Menispermaceae, however, its weak fluorescence and low water solubility impede it for theranostics. We developed here 4-hydroxyl-oxoisoaporphine (OHOA), which has good singlet oxygen-generating ability (0.06), strong fluorescence (0.72) and improved water solubility. OHOA displays excellent fluorescence for cell imaging and exhibits light-induced cytotoxicity against cancer cell. In vitro model of human cervical carcinoma (HeLa) cell proved that singlet oxygen generated by OHOA triggered photosensitized oxidation reactions and exert toxic effect on tumor cells. The MTT assay using HeLa cells verified the low cytotoxicity of OHOA in the dark and high phototoxicity. Confocal experiment indicates that OHOA mainly distributes in mitochondria and western blotting demonstrated that OHOA induces cell apoptosis via the mitochondrial pathway in the presence of light. Our molecule provides an alternative choice as a theranostic agent against cancer cells which usually are in conflict with each other for most traditional theranostic agents. Graphic abstract: [Figure not available: see fulltext.]
Inhibitory activity on cholinesterases produced by aryl-phthalimide derivatives: green synthesis, in silico and in vitro evaluation
Andrade-Jorge, Erik,Padilla-Martínez, Itzia I.,Ruiz-Maciel, Omar,Sánchez-Labastida, Luis A.,Soriano-Ursúa, Marvin A.,Trujillo-Ferrara, José G.
, (2020/05/08)
Background: Alzheimer’s disease (AD) is characterized by cognitive impairment and loss of immediate memory resulting from neuronal death in different brain areas, mainly those producing acetylcholine. Acetylcholinesterase inhibitors improve cognitive function, delay mental deterioration, and reduce other symptoms. Despite being the cornerstone for treating mild–moderate AD, these compounds are only palliative agents and often have severe adverse effects. Recently, butyrylcholinesterase (BuChE) has been found to be involved in AD. The aim of this study was to synthesize a series of six phthalimides with structural relationship with monoamines and evaluate them in vitro and in silico as AChE and BuChE inhibitors. In addition, a modified version of the Bonting and Featherstone method for determining AChE activity was adapted for the assessment of BuChE activity. Results: Six molecules (dioxoisoindolines A–F) were synthesized in good yields using a green chemistry approach. Dioxoisoindolines E and F were more active for AChE, with a Ki of 232 and 193 μM, respectively. Contrarily, dioxoisoindolines C and D showed up to fivefold greater selectivity for BuChE than AchE, with a Ki of 200 and 100 μM, respectively. The competitive inhibitory activity of the latter two molecules was similar to that of the reference compounds. Molecular docking demonstrated the participation of carbonyl carbons and aromatic rings in the high affinity of dioxoisoindoles for cholinesterases. Conclusion: The modified version of the Bonting and Featherstone method was successfully adapted to quantify BuChE activity. Dioxoisoindolines C and D displayed greater inhibition of BuChE versus AChE, with good inhibition of both enzymes. Thus, they are promising lead compounds for developing new BuChE/AChE inhibitors. [Figure not available: see fulltext.]
