Disease relevance of benzothiophene

• Though structurally unrelated to chrysin, an HIV-1 inhibitory benzothiophene also bound selectively to CKII [1].
• PURPOSE: We conducted this phase I trial to determine the safety and toxicity profile of LY353381.HCl-a novel, potent, third-generation selective estrogen receptor modulator (SERM)-because this benzothiophene derivative demonstrated an SERM profile in preclinical studies [2].
• Biodesulfurization of naphthothiophene and benzothiophene through selective cleavage of carbon-sulfur bonds by Rhodococcus sp. strain WU-K2R [3].
• Isopropylbenzene-degrading bacteria, including Pseudomonas putida RE204, transform benzothiophene to a mixture of compounds [4].
• MATERIALS AND METHODS: Cellular models of latent (OM-10.1 and U1) and chronic (8E5) HIV infection were used to evaluate two benzothiophene derivatives, PD 121871 and PD 144795, for an ability to inhibit HIV activation and expression [5].

High impact information on benzothiophene

• Raloxifene (LY139481 HCI) is a benzothiophene derivative that binds to the estrogen receptor and inhibits the effects of estrogen on the uterus [6].
• These results demonstrate that the DNA binding of p53 to the HIV-1 LTR can be modulated by calcineurin and provide a framework to understand the anti-HIV properties of benzothiophene derivatives [7].
• The major one in development is the benzothiophene arzoxiphene (LY353381), which is now in Phase III clinical trial versus tamoxifen [8].
• We selected the benzo[b]thiophene and benzofuran combretastatin analogues 11 (ST2151) and 13 (ST2179) and their phosphate prodrugs (29 and 30) for their high antitumor activity in in vitro and in vivo models [9].
• The organotin-oxomolybdates [(R(3)Sn)(2)MoO(4)].n H(2)O (R=methyl, n-butyl, cyclohexyl, phenyl, benzyl) have been prepared and tested as catalysts for the oxidation of benzothiophene with aqueous hydrogen peroxide, at 35 degrees C and atmospheric pressure [10].

Chemical compound and disease context of benzothiophene

• Dibenzothiophene is degraded to 3-hydroxy-2-formyl benzothiophene by various bacteria, including a strain of Pseudomonas putida that also forms dibenzothiophene sulfone via an alternate pathway [11].
• These results suggest that 4'F-DMA might be an improved benzothiophene SERM with similar antiestrogenic activity to raloxifene but improved metabolic stability and attenuated toxicity, showing that simple chemical modification can abrogate oxidative bioactivation to potentially toxic metabolites without loss of activity [12].
• The benzothiophene selective estrogen receptor modulators (SERMs), raloxifene and arzoxifene, in the clinic or clinical trials for treatment of breast cancer and postmenopausal symptoms, are highly susceptible to oxidative metabolism and formation of electrophilic metabolites [12].
• CI-959, a new benzothiophene cell activation inhibitor, has the capacity to suppress spontaneous polarity and locomotion of Walker carcinosarcoma cells [13].
• The present study tested the hypothesis that a benzothiophene analogue and selective estrogen receptor modulator, LY353381.HCl (LY), reduces tissue infarction after MCA occlusion in estrogen-deficient, ovariectomized female rats [14].

Biological context of benzothiophene

• Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 5. Potency, efficacy, and pharmacokinetic properties of modified C-3 side chain derivatives [15].
• The benzothiophene derivatives also inhibited HIV-1 activation by phorbol ester treatment of OM-10.1 promyelocytes, although no inhibition of cellular differentiation toward a macrophage-like phenotype was observed [5].
• Biotransformation of benzothiophene by isopropylbenzene-degrading bacteria [4].
• Hence, compound 20 (6-(2-imidazolin-2-yl)-2-[4-(2-imidazolin-2-yl)phenyl] benzo[b]thiophene) emerged as the most potent inhibitor of L1210 cell growth (ID50: 0.21 micrograms/ml) [16].
• The benzothiophene derivatives did not inhibit the activity of the HIV-1 trans-activator, Tat, when evaluated in transient transfection assays [5].

Anatomical context of benzothiophene

• Subsequently, GSH adducts of raloxifene were identified in incubations with human liver microsomes; substitution with GSH occurred at the 5- or 7-position of the benzothiophene moiety or at the 3'-position of the phenol ring, with the 7-glutathionyl derivative being most abundant based on LC/MS and NMR analyses [17].
• In the present study, the preliminary in vitro metabolic routes of a series of novel 2-substituted benzothiophene-containing discovery molecules were determined in fresh and cryopreserved hepatocyte suspensions [18].
• Marked suppression of T cells by a benzothiophene derivative in patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis [19].
• METHODS: The biological effects of LY117018, a nonsteroidal antiestrogen benzothiophene derivative, were assessed on a human adenocarcinoma cell line (HCT8 cells), and on DT cells and colorectal cancer derived fibroblasts in primary culture [20].
• Benzothiophene residues were not detected in adipose tissue, liver, and serum of rats in the 200 mg/kg rats, but a small quantity was detected in the urine [21].

Associations of benzothiophene with other chemical compounds

• Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA) [22].
• Benzo[b]furan and indole analogues of some recently identified benzo[b]thiophene inhibitors of tubulin polymerization have been prepared, and their biological activity has been assessed [23].
• Mineralization of the dibenzothiophene biodegradation products 3-hydroxy-2-formyl benzothiophene and dibenzothiophene sulfone [11].
• A new, substituted benzo[b]thiophene carboxylic acid derivative (tritiated) is proposed as an alternative ligand for cytosolic retinoic acid binding protein [24].
• On the other hand, partial antiestrogens, such as hydroxytamoxifen (a triphenylethylene) and LY 117,018 (a benzothiophene) stabilized ER, making it immune to radicicol-induced degradation [25].

Gene context of benzothiophene

• The inhibition of TNF alpha-stimulated HIV expression and the anti-inflammatory property of PD144795, a new benzothiophene derivative, have been recently described [26].
• Carbonic anhydrase inhibitors: inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with benzo[b]thiophene 1,1-dioxide sulfonamides [27].
• A series of benzo[b]thiophene-derived NPY-1 receptor antagonists is described [28].
• Structure-activity relationships of a series of benzothiophene-derived NPY Y1 antagonists: optimization of the C-2 side chain [28].
• The benzothiophene LY329146 reverses the drug resistance phenotype in multidrug resistance protein (MRP1)-overexpressing cells when dosed in combination with MRP1-associated oncolytics doxorubicin and vincristine [29].

Analytical, diagnostic and therapeutic context of benzothiophene

• A bacterial strain, SWU-4, capable of using benzothiophene (BT) as a sole carbon and energy source was isolated from a petroleum-contaminated site in Thailand and identified by 16S rRNA gene sequence analysis to be in the genus of Mycobacterium [30].

References