7501-05-5Relevant academic research and scientific papers
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.
Syntheses and characterization of novel oxoisoaporphine derivatives as dual inhibitors for cholinesterases and amyloid beta aggregation
Li, Yan-Ping,Ning, Fang-Xian,Yang, Meng-Bi,Li, Yong-Cheng,Nie, Min-Hua,Ou, Tian-Miao,Tan, Jia-Heng,Huang, Shi-Liang,Li, Ding,Gu, Lian-Quan,Huang, Zhi-Shu
, p. 1572 - 1581 (2011)
A series of 3-substituted (5c-5f, 6c-6f) and 4-substituted (10a-10g) oxoisoaporphine derivatives were synthesized. It was found that all these synthetic compounds had IC50 values at micro or nano molar range for cholinesterase inhibition, and most of them could inhibit amyloid β (Aβ) self-induced aggregation with inhibition ratio from 31.8% to 57.6%. The structure-activity relationship studies revealed that the derivatives with higher selectivity on AChE also showed better inhibition on Aβ self-induced aggregation. The results from cell toxicity study indicated that most quaternary methiodide salts had higher IC50 values than the corresponding non-quaternary compounds. This study provided potentially important information for further development of oxoisoaporphine derivatives as lead compounds for the treatment of Alzheimer's disease.
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.]
Light-induced activities of novel naphtho[1,8-ef]isoindole-7,8,10(9H)-trione and oxoisoaporphine derivatives towards mosquito larvae
Feng, Hao,Shao, Xusheng,Xu, Qi
supporting information, (2021/07/14)
Infected mosquitoes are significant vectors of dengue, yellow fever, chikungunya, zika and other pathogens. In the view of increasing resistance in mosquito larvae control, photoactivated insecticides is a promising approach by utilizing highly toxic singlet oxygen produced by photosensitizer through irradiation. However, the choice of photosensitizer for mosquito control is limited. Here, we report a novel series of naphtho[1,8-ef]isoindole-7,8,10(9H)-trione and oxoisoaporphines derivatives as excellent type II photosensitizers. Meanwhile, the light-dependent activities against permethrin-susceptible and permethrin-resistant strain of Aedes aegypti mosquito larvae of these compounds were evaluated. Among them, compound 7b was proved to be potential photodynamic insecticide due to its excellent phototoxicity, the LC50 value was 0.19 μg mL?1 under visible light irradiation. The irradiation-generated enhancement in the activity was more than 520-fold. This compound could be the potential candidate in the search for new photoactivated insecticide leads. Importantly, 7b has good fluorescence quantum yield (?F = 0.70), it can be used as a fluorescence indicator in mosquito larvae to observe uptake and morphology change.
Tunable System for Electrochemical Reduction of Ketones and Phthalimides
Chen, Gong,Qiao, Tianjiao,Wang, Yaxin,Zhang, Jian,Zhao, Jianyou
supporting information, p. 3297 - 3302 (2021/10/14)
Herein, we report an efficient, tunable system for electrochemical reduction of ketones and phthalimides at room temperature without the need for stoichiometric external reductants. By utilizing NaN3 as the electrolyte and graphite felt as both the cathode and the anode, we were able to selectively reduce the carbonyl groups of the substrates to alcohols, pinacols, or methylene groups by judiciously choosing the solvent and an acidic additive. The reaction conditions were compatible with a diverse array of functional groups, and phthalimides could undergo one-pot reductive cyclization to afford products with indolizidine scaffolds. Mechanistic studies showed that the reactions involved electron, proton, and hydrogen atom transfers. Importantly, an N3/HN3 cycle operated as a hydrogen atom shuttle, which was critical for reduction of the carbonyl groups to methylene groups.
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.]
Graphene Oxide: A Metal-Free Carbocatalyst for the Synthesis of Diverse Amides under Solvent-Free Conditions
Patel, Khushbu P.,Gayakwad, Eknath M.,Patil, Vilas V.,Shankarling, Ganapati S.
supporting information, p. 2107 - 2116 (2019/03/26)
An environmentally friendly, inexpensive, carbocatalyst, graphene oxide (GO) promoted efficient, metal-free transamidation of various carboxamides with aliphatic, cyclic, and aromatic amines is demonstrated. The protocol is equally applicable to phthalimide, urea, and thioamide determining its adaptability. The oxygenated functionalities such as carbonyl (?C=O), epoxy (?O?), carboxyl (?COOH) and hydroxyl (?OH), present on graphene oxide surface impart acidic properties to the catalyst. The graphene oxide being heterogeneous in nature, work efficiently under solvent-free reaction conditions providing desired products in good to excellent yields. The one-pot synthesis of 2,3-Dihydro-5H-benzo[b]-1,4-thiazepin-4-one moiety by GO catalyzed Aza Michael addition followed by intramolecular transamidation is also described. A plausible reaction mechanistic pathway involving H-bonding is discussed. The graphene oxide can be recycled and reused up to five cycles without much loss in catalytic activity. (Figure presented.).
Isoindolinone Synthesis: Selective Dioxane-Mediated Aerobic Oxidation of Isoindolines
Thapa, Pawan,Corral, Esai,Sardar, Sinjinee,Pierce, Brad S.,Foss, Frank W.
supporting information, p. 1025 - 1034 (2019/01/24)
N-Alkyl and N-aryl-isoindolinones were prepared by a dioxane-mediated oxidation of isoindoline precursors. The transformation exhibits unique chemoselectivity for isoindonlines. A chiral tertiary (3°)-benzylic position was not racemized during oxidation, and methyl indoprofen was prepared by late stage oxidation. Mechanistic studies suggest a selective H atom transfer, which avoids many known oxidation (by-)products of isoindolinones.
Isoindolines/isoindoline-1,3-diones as AChE inhibitors against Alzheimer’s disease, evaluated by an improved ultra-micro assay
Andrade-Jorge, Erik,Sánchez-Labastida, Luis A.,Soriano-Ursúa, Marvin A.,Guevara-Salazar, Juan A.,Trujillo-Ferrara, José G.
, p. 2187 - 2198 (2018/08/11)
Alzheimer’s disease (AD), the most common form of dementia, is characterized by a progressive degeneration of the brain that leads to loss of memory and deterioration of others cognitive functions. The only drugs currently approved for treating AD are AChE inhibitors (AChEIs). We previously tested a novel isoindoline-1,3-dione, finding potent inhibition of AChE, in part because the two carbonyl groups of phthalimide facilitate hydrogen bonds with the enzyme. The aims of the present study were: (A) To achieve a faster and cheaper technique with a reduced quantity of reactive, without significant difference in the validation of the results, by modifying the version of the method described by Bonting and Featherstone. (B) To test new isoindolines and dioxoisoindolines as AChEIs and see if the carbonyl group is really important for affinity. Both families of compounds (isoindolines and dioxoisoindolines) had an inhibitory effect. The enzymatic inhibitions produced by isoindolines were uncompetitive, whereas that evoked by dioxoisoindolines were competitive. One of the isoindoline derivatives (IsoB with a Ki of 88–160μM) showed about 5-fold greater inhibition of AChE than its corresponding dioxoisoindoline. According to molecular docking performed, dioxoisoindolines apparently interact with the catalytic active site, the peripheral anionic site, and the aromatic patch, which can explain the kind of inhibition observed. Due to the uncompetitive inhibition of isoindolines, their inhibitory behavior could not be explored in silico. We afforded a faster and more efficient method, while yielding similar results than Bonting and Featherstone method. Additionally, we demonstrated that carbonyl group affects the kind of inhibition and the affinity.
