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IUCrData Jul 2023The title compound, CHNO, crystallizes with ' = 2 in space group 2 with the two independent mol-ecules having almost the same conformation, differing mostly at the end...
The title compound, CHNO, crystallizes with ' = 2 in space group 2 with the two independent mol-ecules having almost the same conformation, differing mostly at the end of the butanamide chain. A local inversion center near 1/8, 3/4, relates the two mol-ecules, as is common for structures in this space group with ' = 2. The mol-ecule crystallizes as the keto tautomer, and the β-diketone moieties are twisted out of planarity, with O-C⋯C-O pseudo torsion angles of -74.4 (5) and -83.9 (5)°. The N-H group of each independent mol-ecule donates an inter-molecular hydrogen bond to an amide carbonyl oxygen atom by positive or negative translations along the axis, thus forming anti-parallel chains propagating in the [010] direction.
PubMed: 37937129
DOI: 10.1107/S2414314623005655 -
IUCrData Apr 2023The title compound, CHNO, crystallizes with a disordered nitro group in twinned crystals. Both the meth-oxy group and the acetamide groups are nearly coplanar with the...
The title compound, CHNO, crystallizes with a disordered nitro group in twinned crystals. Both the meth-oxy group and the acetamide groups are nearly coplanar with the phenyl ring, and the C-N-C-O torsion angle [0.2 (4)°] is also insignificantly different from zero. Overall, the 12-atom meth-oxy-phenyl-acetamide group is nearly planar, with an r.m.s. deviation of 0.042 Å. The nitro group is twisted out of this plane by about 30°, disordered into two orientations with opposite senses of twist. In the crystal, the N-H group donates a hydrogen bond to a nitro oxygen atom, generating chains propagating in the [101] direction. The amide carbonyl oxygen atom is not involved in the hydrogen bonding.
PubMed: 37151207
DOI: 10.1107/S2414314623002985 -
Microorganisms Jul 2023Phenacetin, an antipyretic and analgesic drug, poses a serious health risk to both humans and aquatic organisms, which is of concern since this micropollutant is...
Phenacetin, an antipyretic and analgesic drug, poses a serious health risk to both humans and aquatic organisms, which is of concern since this micropollutant is frequently detected in various aquatic environments. However, rare pure bacterial cultures have been reported to degrade phenacetin. Therefore, in this study, the novel phenacetin-degrading strain PNT-23 was isolated from municipal wastewater and identified as a sp. based on its morphology and 16S rRNA gene sequencing. The isolated strain could completely degrade 100 mg/L phenacetin at an inoculum concentration of OD 1.5 within 80 h, utilizing the micropollutant as its sole carbon source for growth. Strain PNT-23 exhibited optimal growth in LB medium at 37 °C and a pH of 7.0 with 1% NaCl, while the optimal degradation conditions in minimal medium were 30 °C and a pH of 7.0 with 1% NaCl. Two key intermediates were identified during phenacetin biodegradation by the strain PNT-23: N-acetyl-4-aminophenol and 4-aminophenol. This study provides novel insights into the biodegradation of phenacetin using a pure bacterium culture, expands the known substrate spectra of strains and presents a potential new candidate for the microbial removal of phenacetin in a diverse range of environments.
PubMed: 37630522
DOI: 10.3390/microorganisms11081962 -
IUCrData Aug 2020In the title compound, CHNO, the torsion angles about the bonds to the benzene ring are less than 4°, except for the nitro groups, which are twisted out of the ring...
In the title compound, CHNO, the torsion angles about the bonds to the benzene ring are less than 4°, except for the nitro groups, which are twisted out of the ring plane by 25.27 (3) and 43.63 (2)°. The N-H group forms a bifurcated hydrogen bond, with an intra-molecular component to a nitro group O atom and an inter-molecular component to the other nitro group, thereby forming chains propagating in the [010] direction. Several weak C-H⋯O inter-actions are also present.
PubMed: 36338512
DOI: 10.1107/S2414314620011219 -
Heliyon Jun 2022Direct evidence of Triphala-drug interactions has not been provided to date.
CONTEXT
Direct evidence of Triphala-drug interactions has not been provided to date.
OBJECTIVE
This study was aimed to determine the effects of Triphala on cytochrome P450 (CYP) isoforms and P-glycoprotein (P-gp) and to investigate pharmacokinetic interactions of Triphala with CYP-probes in rats.
MATERIALS AND METHODS
Effects of Triphala on the activities of CYP isoforms and P-gp were examined using human liver microsomes (HLMs) and Caco-2 cells, respectively. Pharmacokinetic interactions between Triphala and CYP-probes (i.e., phenacetin and midazolam) were further examined in rats.
RESULTS
Triphala extract inhibited the activities of CYP isoforms in the order of CYP1A2>3A4>2C9>2D6 with the IC values of 23.6 ± 9.2, 28.1 ± 9.8, 30.41 ± 16.7 and 93.9 ± 27.5 μg/mL, respectively in HLMs. It exhibited a non-competitive inhibition of CYP1A2 and 2C9 with the values of 23.6 and 30.4 μg/mL, respectively, while its inhibition on CYP3A4 was competitive manner with the i values of 64.9 μg/mL. The inhibitory effects of Triphala on CYP1A2 and 3A4 were not time-dependent. Moreover, Triphala did not affect the P-gp activity in Caco-2 cells. Triphala, after its oral co-administration at 500 mg/kg, increased the bioavailabilities of phenacetin and midazolam by about 61.2% and 40.7%, respectively, in rats.
DISCUSSION AND CONCLUSIONS
Increases observed in the bioavailabilities of phenacetin and midazolam after oral co-administration of Triphala in rats provided a direct line of evidence to show Triphala-drug interactions inhibition of CYP1A and CYP3A activities, respectively. These results, together with the lack of time-dependency of CYP 1A2 and 3A4 inhibition , suggested that the inhibitory effect of Triphala is primarily reversible.
PubMed: 35785236
DOI: 10.1016/j.heliyon.2022.e09764 -
Molecular Pharmaceutics Mar 2021Hydrolytic reactions constitute an important pathway of drug metabolism and a significant route of prodrug activation. Many ophthalmic drugs and prodrugs contain ester...
Hydrolytic reactions constitute an important pathway of drug metabolism and a significant route of prodrug activation. Many ophthalmic drugs and prodrugs contain ester groups that greatly enhance their permeation across several hydrophobic barriers in the eye before the drugs are either metabolized or released, respectively, hydrolysis. Thus, the development of ophthalmic drug therapy requires the thorough profiling of substrate specificities, activities, and expression levels of ocular esterases. However, such information is scant in the literature, especially for preclinical species often used in ophthalmology such as rabbits and pigs. Therefore, our aim was to generate systematic information on the activity and expression of carboxylesterases (CESs) and arylacetamide deacetylase (AADAC) in seven ocular tissue homogenates from these two species. The hydrolytic activities were measured using a generic esterase substrate (4-nitrophenyl acetate) and, in the absence of validated substrates for rabbit and pig enzymes, with selective substrates established for human CES1, CES2, and AADAC (d-luciferin methyl ester, fluorescein diacetate, procaine, and phenacetin). Kinetics and inhibition studies were conducted using these substrates and, again due to a lack of validated rabbit and pig CES inhibitors, with known inhibitors for the human enzymes. Protein expression levels were measured using quantitative targeted proteomics. Rabbit ocular tissues showed significant variability in the expression of CES1 (higher in cornea, lower in conjunctiva) and CES2 (higher in conjunctiva, lower in cornea) and a poor correlation of CES expression with hydrolytic activities. In contrast, pig tissues appear to express only CES1, and CES3 and AADAC seem to be either low or absent, respectively, in both species. The current study revealed remarkable species and tissue differences in ocular hydrolytic enzymes that can be taken into account in the design of esterase-dependent prodrugs and drug conjugates, the evaluation of ocular effects of systemic drugs, and in translational and toxicity studies.
Topics: Animals; Carboxylesterase; Eye; Female; Humans; Hydrolysis; Male; Nitrophenols; Prodrugs; Proteomics; Rabbits; Substrate Specificity; Swine
PubMed: 33595329
DOI: 10.1021/acs.molpharmaceut.0c01154 -
Trends in Psychiatry and Psychotherapy Jul 2019Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of...
INTRODUCTION
Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence.
METHOD
We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained.
RESULTS
Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%).
CONCLUSION
Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.
Topics: Adolescent; Adult; Brazil; Cocaine-Related Disorders; Crack Cocaine; Drug Contamination; Female; Hair; Humans; Levamisole; Lidocaine; Male; Phenacetin; Young Adult
PubMed: 31314858
DOI: 10.1590/2237-6089-2017-0143 -
Molecules (Basel, Switzerland) Jul 2021The thermodynamic properties of phenacetin in solid state and in saturated conditions in neat and binary solvents were characterized based on differential scanning...
The thermodynamic properties of phenacetin in solid state and in saturated conditions in neat and binary solvents were characterized based on differential scanning calorimetry and spectroscopic solubility measurements. The temperature-related heat capacity values measured for both the solid and melt states were provided and used for precise determination of the values for ideal solubility, fusion thermodynamic functions, and activity coefficients in the studied solutions. Factors affecting the accuracy of these values were discussed in terms of various models of specific heat capacity difference for phenacetin in crystal and super-cooled liquid states. It was concluded that different properties have varying sensitivity in relation to the accuracy of heat capacity values. The values of temperature-related excess solubility in aqueous binary mixtures were interpreted using the Jouyban-Acree solubility equation for aqueous binary mixtures of methanol, DMSO, DMF, 1,4-dioxane, and acetonitrile. All binary solvent systems studied exhibited strong positive non-ideal deviations from an algebraic rule of mixing. Additionally, an interesting co-solvency phenomenon was observed with phenacetin solubility in aqueous mixtures with acetonitrile or 1,4-dioxane. The remaining three solvents acted as strong co-solvents.
Topics: Phenacetin; Physical Phenomena; Solubility; Solvents; Temperature; Thermodynamics; Water
PubMed: 34279418
DOI: 10.3390/molecules26134078 -
Frontiers in Oncology 2021Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. If primary cutaneous melanoma is mostly...
Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. If primary cutaneous melanoma is mostly treated with a curative wide local excision, malignant melanoma has a poor prognosis and needs other therapeutic approaches. Angiogenesis is a normal physiological process essential in growth and development, but it also plays a crucial role in crossing from benign to advanced state in cancer. In melanoma progression, angiogenesis is widely involved during the vertical growth phase. Currently, no anti-angiogenic agents are efficient on their own, and combination of treatments will probably be the key to success. In the past, phenacetin was used as an analgesic to relieve pain, causing side effects at large dose and tumor-inducing in humans and animals. By contrast, low-dilution is often used in skin febrile exanthema, patches profusely scattered on limbs, headache, or flushed face without side effects. Herein are described the , , and anti-angiogenic and anti-tumoral potentials of low-dilution in a B16F1 tumor model and endothelial cells. We demonstrate that low-diluted inhibits tumor growth and tumor vascularization and thus increases the survival time of B16F1 melanoma induced-C57BL/6 mice. Moreover, modulates the lung metastasis in a B16F10 induced model. and , we evidence that low-diluted inhibits the migration and the recruitment of endothelial cells and leads to an imbalance in the pro-tumoral macrophages and to a structural malformation of the vascular network. All together these results demonstrate highly hopeful anti-tumoral, anti-metastatic, and anti-angiogenic effects of low-dilution on melanoma. Continued studies are needed to preclinically validate low-dilution as a complementary or therapeutic strategy for melanoma treatment.
PubMed: 33747916
DOI: 10.3389/fonc.2021.597503