Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxetanocin G(9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine, OXT-G) is a potent and selective agent against human cytomegalovirus (HCMV). In this study we synthesized the triphosphate form of OXT-G, OXT-GTP, and examined its effect on the activities of HCMV DNA polymerase, herpes simplex type 2 (HSV-2) DNA polymerase and human DNA polymerase alpha. OXT-GTP was found to inhibit all these polymerases in a competitive manner with respect to dGTP. The Km for dGTP and the Ki for OXT-GTP of HCMV DNA polymerase were 0.86 and 0.53 mu M, respectively, while the corresponding values of DNA polymerase alpha were 2.2 and 3.6 mu M, respectively. HPLC analysis using [3H]OXT-G also revealed that OXT-G was converted to its triphosphate form 7- to 8-fold more efficiently in HCMV-infected cells than in uninfected cells. The results suggest that both the preferential phosphorylation of OXT-G in HCMV-infected cells and the preferential inhibition of HCMV DNA polymerase by OXT-GTP may contribute towards the selective activity of OXT-G against HCMV replication.
 ...
PMID:Mechanism of inhibition of human cytomegalovirus replication by oxetanocin G. 185 Oct 5

The antiviral activity of a new guanosine analog, 9-(2-deoxy-2-hydroxymethyl-beta-D-erythrooxetanosyl)guanine (OXT-G), against guinea pig cytomegalovirus (GPCMV) was evaluated both in vitro and in vivo. In the plaque reduction assay, the median effective concentration (EC50) of OXT-G, ganciclovir (DHPG) and acyclovir (ACV) against GPCMV was 0.03, 6.4 and 52 micrograms/ml, respectively. The selectivity index, based on the ratio of the median inhibitory concentration for cell growth of guinea pig embryo fibroblasts to the median effective concentration for GPCMV plaque formation, was about 100-fold higher than that of DHPG. In an in vivo study, Hartley guinea pigs infected with GPCMV were treated with OXT-G or DHPG (20 mg/kg/day) for 2 weeks, and it was found that virus titers in the salivary gland were 70-fold lower in OXT-G-treated guinea pigs than in DHPG-treated animals. The results indicate that OXT-G was more potent and selective against GPCMV infection than DHPG.
 ...
PMID:Antiviral effect of oxetanocin G against guinea pig cytomegalovirus infection in vitro and in vivo. 217 63

A series of new compounds, carbocyclic oxetanocins, have been synthesized and their anti-herpesvirus activity determined. Carbocyclic oxetanocin G (OXT-G) was most active against herpes simplex virus (HSV) and human cytomegalovirus (HCMV) among carbocyclic oxetanocins tested; the median effective concentrations (EC50) for HSV-1, -2, and HCMV were 0.23, 0.04 and 0.40 micrograms/ml, respectively. The EC50 value of carbocyclic OXT-G against HSV-2 was significantly lower than those of acyclovir, ganciclovir (DHPG) and OXT-G, while the value for HCMV was comparable to those of DHPG and OXT-G. Carbocyclic OXT-G showed much higher activity against TK+ HSV-2 than against a TK- mutant, suggesting that this compound is a good substrate for HSV-2-induced TK. The antiviral activity of the compound was only partially reversed even by the addition of 100-fold excess deoxyguanosine. The results suggest that the mode of action of carbocyclic OXT-G is different from that of OXT-G.
 ...
PMID:Anti-herpesvirus activity of carbocyclic oxetanocin G in vitro. 255 11

A novel nucleoside with an oxetanosyl-N-glycoside has been recently isolated from a culture filtrate from Bacillus megaterium and named oxetanocin A (N. Shimada, S. Hasegawa, T. Harada, T. Tomisawa, A. Fujii, and T. Takita, J. Antibiot. 39:1623-1625, 1986). In this study, we evaluated the antiherpesvirus activity of oxetanocin A and its derivatives and found that 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine (OXT-G) was very potent and selective in inhibiting the replication of human cytomegalovirus (HCMV) in vitro. The median effective concentration for HCMV strain AD169 was 1.0 microgram/ml, and that for herpes simplex virus type 2 strain 186 was 3.5 micrograms/ml. The selectivity index, based on the ratio of the median inhibitory concentration for cell growth of human diploid fibroblasts to the median effective concentration for HCMV plaque formation, was more than 300. The synthesis of HCMV-induced late polypeptides such as the 150,000-molecular-weight capsid and the 68,000-molecular-weight major matrix proteins was strongly suppressed when OXT-G (5 micrograms/ml) was added to the cultures at the beginning of infection. At this concentration of OXT-G, the amount of HCMV DNA detected in the drug-treated infected cells was less than 1/10 of that detected in the infected control cells. The results suggest that the mode of action of OXT-G is inhibition of viral replication by impairing the viral DNA synthesis.
 ...
PMID:Selective inhibition of human cytomegalovirus replication by a novel nucleoside, oxetanocin G. 284 38

Our study of 390 patients enrolled in a birthing suite program revealed that antepartum or intrapartum problems allowed only 160 (41%) to actually give birth in the birthing suite. Antepartum complications included premature labor in ten (2.5%), premature ruptured membranes in 31 (8%), postdatism in 50 (13%), preeclampsia in 27 (7%), and diabetes mellitus in five (1.3%). Intrapartum complications included meconium in 62 (16%), arrest of labor in 64 (16%), oxytocin use in 85 (22%), and fetal heart rate decelerations in 28 (7%). Two hundred ninety-seven births (76%) were spontaneous. Forty-two low-forceps deliveries (10%), 12 mid-forceps deliveries (3%), and 39 cesarean sections (10%) were done in the traditional labor and delivery suite. Puerperal complications included one uterine inversion, two cases of placenta accreta, one rectovaginal fistula, and two requirements of blood transfusion. Neonatal morbidity included 22 low Apgar scores (7%), two shoulder dystocia, three cytomegalovirus infestations, and one lethal anomaly. Six infants had meconium aspiration, two with severe hypoxia. Any of these complications would overwhelm the patient in home birth. Intense prenatal screening may decrease some risk factors, but the intrapartum period was found to pose unacceptable risks for home birth in this population.
 ...
PMID:Home birth: negative implications derived from a hospital-based birthing suite. 682 92

A new procedure to introduce the fluorine into the carbocycle of carbocyclic oxetanocin in A (C.OXT-A) was developed. The cyclobutanols 5 and 10, obtainable from the 2,3-di-O-benzoate 3, were condensed with 6-chloropurine using Mitzunobu reaction to give the cyclobutyl nucleosides 6 and 11, respectively. Addition of iodine fluoride to compound 6 afforded [(1R*,2S*,3R*)-isomer 7 as a sole addition product, which was converted to 1. This compound (1) exhibited a broad spectrum of antiviral activity, especially against human cytomegalovirus. Also partial depretection of 11 and successive fluoridation using DAST gave the fluoromethyl derivatives from which another target compounds 2a,b were obtained.
 ...
PMID:Synthesis of carbocyclic oxetanocin analogs bearing fluorine and their antiviral activities. 884 1

The inhibitory activities of acyclovir (ACV), 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), ganciclovir (GCV), 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine (OXT-G), and (+)-9-[(1R,2R,3S)-2,3-bis(hydroxymethyl)Cyclobutyl]guanine (cOXT-G) on the replication of wild-type and thymidine kinase (TK)-negative strains of herpes simplex virus types 1 and 2 and varicella-zoster virus (VZV) and the wild-type strain of human cytomegalovirus were tested to clarity whether the phosphorylation of these compounds is catalyzed by viral TK or other enzymes. ACV and BV-araU had little effect on the replication of TK-negative virus strains. On the other hand, GCV, OXT-G, and cOXT-G inhibited the replication of TK-negative VZV at concentrations 10 times higher than those at which they inhibited wild-type VZV, indicating that a kinase other than TK phosphorylates GCV and OXT-G in VZV-infected cells. GCV phosphorylation activity was not detected in VZV-infected cell lysates; therefore, this activity was evaluated in COS 1 cells expressing viral TK and viral protein kinase (PK). The COS 1 cells expressing VZV TK were shown to be susceptible to all compounds tested. In contrast, VZV Pk-expressing COS 1 cells were susceptible to only GCV, OXT-G, and cOXT-G. These results suggest that VZV PK phosphorylates some nucleoside analogs, for example, GCV, OXT-G, and cOXT-G. This phosphorylation pathway may be important in the anti-VZV activities of some nucleoside analogs.
 ...
PMID:Analysis of phosphorylation pathways of antiherpesvirus nucleosides by varicella-zoster virus-specific enzymes. 884 52