Disease relevance of NSC3108

• Design and optimization of tricyclic phtalimide analogues as novel inhibitors of HIV-1 integrase [1].
• Allergic contact dermatitis from N-(cyclohexylthio) phthalimide in a playground fitter [2].
• Three representative examples N-[2-pyridinyl-1-oxide) methyl] phthalimide 8, 1-[N-2-phthalimidoethyl]-3,4-dihydroiso-quinoline 12, and 1-[N-(2-(1,2,3,4-tetrahydro-2-quinolinyl)] ethylphthalimide 14 were shown to inhibit L1210 leukemia DNA synthesis whereas RNA synthesis was not inhibited at 25-100 uM [3].
• The two compounds containing a phthalimide moiety (compounds 3a and 3b) showed significant and selective cytotoxicity against the breast cancer cell line MDA-MB231 [4].
• However, a comparison of these N-substituted adamantylester imides with the series published previously, indicated that the incorporation of L-alanine and L-phenylalanine into the phthalimide moiety was the best choice regardless of the series and leads to antimicrobial activity against Staphylococcus aureus strains [5].

Psychiatry related information on NSC3108

• The present study investigated the influence of BM-78, BM-121 (gamma-aminobutyric acid amide derivatives) and BM-42, BM-43 (phthalimide precursors of BM-78 and BM-121) on the spontaneous locomotor activity and on the picrotoxin-induced seizures [6].

High impact information on NSC3108

• The chemical efficiencies of these processes are not significantly affected by (1) the lengths of the peptide chains separating the phthalimide and alpha-amidosilane or alpha-amidocarboxylate centers and (2) the nature of the penultimate cation radical alpha-heterolytic fragmentation process (i.e., desilylation vs decarboxylation) [7].
• On the contrary, (S)-thalidomide is preferentially metabolized by hydroxylation in the phthalimide moiety, resulting in the formation of (S)-5-hydroxythalidomide [8].
• As a second step in this process, altering the phthalimide moiety to optimize interactions in the guanine-binding pocket of GPRT is expected to lead to compounds with promising activity against G. lamblia PRT [9].
• Previous structure-activity relationships (SAR) revealed two positively charged centers and two lateral phthalimide moieties in a defined arrangement to be essential of a high allosteric potency [10].
• Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established ligands of the common allosteric binding site of muscarinic M(2) receptors [10].

Biological context of NSC3108

• Kinetics of self-decomposition and hydrogen atom transfer reactions of substituted phthalimide N-oxyl radicals in acetic acid [11].
• Crucial to this success was a very unorthodox phthalimide cleavage procedure, C8 azidation prior to aziridination and late stage alkylation of the 5' amino group with iodoethanol necessitated by the high degree of lability endowed by the aryl azide moiety [12].
• In this analogous series of phthalimide derivatives, minor chemical changes affected dramatically the compounds' pharmacokinetics [13].
• Development of new CoMFA and CoMSIA 3D-QSAR models for anti-inflammatory phthalimide-containing TNFalpha modulators [14].
• Hexane-bisammonium-type compounds containing lateral phthalimide moieties are known to have a rather high affinity for the allosteric site of muscarinic M2 receptors [15].

Anatomical context of NSC3108

• The semicarbazones, thiosemicarbazones and acetyl-hydrazones of phthalimide, o-benzosulfimide, naphthalimide and diphenimide demonstrated potent cytotoxicity against murine and human leukemia cell growth and cultured cell growth from human solid tumors [16].
• The anticancer property of a new alpha-methylene-gamma-lactone derivative of phthalimide (2, NSC 640168) was evaluated in two murine ascitic tumors namely Ehrlich ascites carcinoma (EAC) and sarcoma-180 (S-180) by in vivo screenings and in a battery of human tumor cell lines by in vitro screening [17].
• A series of cyclic imides, which possess a bulkier N-ring structure than phthalimide and saccharin, were shown to suppress LDL receptor binding, internalization and degradation of isolated rat hepatocytes, foam cells, human fibroblasts and mouse macrophages [18].

Associations of NSC3108 with other chemical compounds

• Amino acid-derived phthalimide and saccharin derivatives as inhibitors of human leukocyte elastase, cathepsin G, and proteinase 3 [19].
• Phthalimide analogues were effective in accelerating biliary excretion of cholesterol and blocking its absorption from the gut [20].
• N-hydroxyphthalimide, a simple derivative of phthalimide, was more effective than thalidomide and was also the most effective of the compounds assayed in suppressing the IgM plaque and TNF-alpha responses, but it did not enhance the IL-2 response, instead, it significantly suppressed it [21].
• Amino acid-derived phthalimide and saccharin derivatives have been investigated for their inhibitory activity toward the serine proteinases human leukocyte elastase, cathepsin G, and proteinase 3 [19].
• Apparently, its affinity for the allosteric site in NMS-occupied receptors is 20fold higher compared with the phthalimide containing parent compound W 84 [15].

Gene context of NSC3108

• Design and synthesis of phthalimide-type histone deacetylase inhibitors [22].
• This led us to explore the possibility of using expression of one of the major stress genes, hsp70, in Drosophila as a biomarker against phthalimide group of chemicals, which may accordingly provide an early indication of exposure to these hazardous chemicals [23].
• Replacement of the phthalimide moiety by substituted benzamides led to retention of 5-HT1A affinity but to no improvement in selectivity, whereas replacement by alkyl amides proved beneficial, leading to an improvement in affinity and selectivity [24].
• Some phthalimide analogs, included PP-33 [2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione] and its 4,5,6,7-tetrafluora derivative FPP-33), also showed such an inducer-specific bidirectional TNF-alpha production-regulating activity [25].
• A novel pyrolysis GC-ECD technique that quantified the thermal degradation product phthalimide had pg sensitivity suitable to detect the trace amounts of Folpet that permeated [26].

Analytical, diagnostic and therapeutic context of NSC3108

• Certain differences established between results of thin-layer chromatography, on the one hand, and 15N studies, on the other, are likely to support the assumption that phthalimide is further metabolised by splitting the imide ring yielding phthalamic acid [27].
• In addition the nucleic acid hybridisation properties of a thymidyl-pentamer, T5-POM, with an N-terminal phthalimide group were evaluated using both UV spectroscopy and surface plasmon resonance (SPR) [28].

References