(-)-Agelasidine A Induces Endoplasmic Reticulum Stress-Dependent Apoptosis in Human Hepatocellular Carcinoma.

Liver cancers, such as hepatocellular carcinoma (HCC), are a highly prevalent cause of cancer-related deaths. Current treatments to combat liver cancer are limited. (-)-Agelasidine A, a compound isolated from the methanol extract of Agelasnakamurai, a sesquiterpene guanidine derived from sea sponge, has antibacterial activity. We demonstrated its anticancer capabilities by researching the associated mechanism of (-)-agelasidine A in human liver cancer cells. We found that (-)-agelasidine A significantly reduced viability in Hep3B and HepG2 cells, and we determined that apoptosis was involved in the (-)-agelasidine A-induced Hep3B cell deaths. (-)-Agelasidine A activated caspases 9, 8, and 3, as well as PARP. This effect was reversed by caspase inhibitors, suggesting caspase-mediated apoptosis in the (-)-agelasidine A-treated Hep3B cells. Moreover, the reduced mitochondrial membrane potential (MMP) and the release of cytochrome c indicated that the (-)-agelasidine A-mediated mitochondrial apoptosis was mechanistic. (-)-Agelasidine A also increased apoptosis-associated proteins (DR4, DR5, FAS), which are related to extrinsic pathways. These events were accompanied by an increase in Bim and Bax, proteins that promote apoptosis, and a decrease in the antiapoptotic protein, Bcl-2. Furthermore, our results presented that (-)-agelasidine A treatment bridged the intrinsic and extrinsic apoptotic pathways. Western blot analysis of Hep3B cells treated with (-)-agelasidine A showed that endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated PERK, phosphorylated eIF2α, ATF4, truncated ATF6, and CHOP) were upregulated. Moreover, 4-PBA, an ER stress inhibitor, could also abrogate (-)-agelasidine A-induced cell viability reduction, annexin V+ apoptosis, death receptor (DR4, DR5, FAS) expression, mitochondrial dysfunction, and cytochrome c release. In conclusion, by activating ER stress, (-)-agelasidine A induced the extrinsic and intrinsic apoptotic pathways of human HCC.

Hydrochars from pinewood for adsorption and nonradical catalysis of bisphenols.

In the present study, hydrochars (HCs) were prepared from pinewood biomass by high-temperature pyrolysis and applied as environmental-friendly adsorbents and catalysts in the removal of bisphenol F (BPF) and bisphenol S (BPS) from water. It was found that the structural oxygen defects on hydrochars not only enhance the specific surface area for adsorption of the bisphenols, but also function as an electron conductor for molecular oxygen activation in nonradical pathways. The hydrochar pyrolyzed at 800 °C (HC-800) showed the superior adsorption and catalytic performances toward BPS and BPF removals in a wide pH range, and the removal efficiencies were hardly inhibited by the coexistent inorganic anions and humic acid. Particularly, the nonradical reaction is the dominated catalytic oxidation process in a H2O2-HC-800 system, different from the traditional radical-based process with persistent free radicals on hydrochars derived from low-temperature pyrolysis. This study provides a novel route toward the efficient removal of endocrine disrupting compounds via the synergistic adsorption and nonradical catalysis.

Efficient degradation of refractory organic contaminants by zero-valent copper/hydroxylamine/peroxymonosulfate process.

Degradation of naproxen, bisphenol S and ibuprofen in a hydroxylamine enhanced zero-valent copper (Cu0) catalyzed peroxymonosulfate system was investigated for the first time. We found that hydroxylamine addition accelerated the reduction of Cu2+ to Cu+ as well as the corrosion of Cu0, and environmental friendly gas nitrogen was the main product of hydroxylamine. Additionally, hydroxyl radical and sulfate radical were identified to be the dominant reaction species by competitive experiments. The degradation of naproxen, bisphenol S and ibuprofen kept highly efficient in the pH range of 3.0-7.0 in Cu0/hydroxylamine/peroxymonosulfate process, with their degradation products identified by HPLC-MS, which showed that Cu0/hydroxylamine/peroxymonosulfate system could be an alternative to remove non-steroidal antiinflammatory drugs or plasticizers in wastewater. Furthermore, the effects of Cu0, hydroxylamine and peroxymonosulfate dosage were studied and optimized by a BBD based response surface model. This study provided a method to solve the disadvantages of Cu0/peroxymonosulfate systems, and gave a promising method to enhance the efficiencies of ZVMs activated system such as iron, cobalt and copper.

Contamination status of bisphenol A and its analogues (bisphenol S, F and B) in foodstuffs and the implications for dietary exposure on adult residents in Zhejiang Province.

An effective method has been developed for the simultaneous determination of four bisphenols (bisphenol A, S, F and B) in various foodstuffs. The contaminants were extracted by QuEChERS-based strategy and subjected to ion-exchange solid-phase extraction for further clean-up. The critical variables were screened by Plackett-Burman design and then optimized by central composite design. Under the optimized conditions, satisfactory accuracy (recoveries 76%-116%) and precision (RSDs < 12%) were achieved. The established method was then used to assess the contamination status of 379 real samples. Bisphenol A was demonstrated to be the predominant bisphenol with highest incidence (79.7%) and average concentration (14.3 µg/kg). The positive rates (mean concentration) of bisphenol S, F and B were 37.7% (1.6 µg/kg), 26.9% (1.4 µg/kg) and 0.0% (not detected), respectively. Finally, the daily dietary intakes of ∑4bisphenolsfor adult residents were estimated (55.9-76.1 ng/kg bw/day) according to the contamination concentrations and the daily recommended intakes.

Preparation of core-shell structured magnetic covalent organic framework nanocomposites for magnetic solid-phase extraction of bisphenols from human serum sample.

Core-shell structured magnetic covalent organic framework (Fe3O4@COF) nanocomposites were synthesized via a facile approach at room temperature and explored as an absorbent for magnetic solid-phase extraction (MSPE) of bisphenols (BPs) from human serum sample. The as-prepared Fe3O4@COF nanocomposites with core-shell structure possessed high specific surface area (181.36m2/g), uniform mesoporous size (~ 3.6nm), high saturation magnetization (42.7emu/g), and excellent thermal and chemical stability, rendering it as an ideal adsorbent with high adsorption efficiency and size selectivity. The experimental parameters influencing extraction efficiency, including adsorbent dosage, extraction time, pH and ion strength, desorption solvent and time, were investigated in detail. Taking these advantages together, a simple, fast, effective and sensitive method that MPSE followed by HPLC-MS, was proposed to detect five BPs, which exhibited good linearity (r > 0.9982) within the concentration ranges of 0.1-50µg/L. Moreover, the low detection limits (1.0-78.1ng/L), signal-to-noise ratio (S/N = 3), the high enrichment factors (56-95 fold), and good recoveries (93.0-107.8%) with relative standard deviations (RSDs) less than 3.4% for inter-day and 6.9% for intra-day were achieved. The developed method was also successfully applied to the analysis of trace BPs in human serum sample, which demonstrated the most promising potential of the Fe3O4@COF nanocomposites as good adsorbent in sample pretreatment.

Graphene oxide-doping improves the biocompatibility and separation performance of polyethersulfone hollow fiber membranes for bioartificial kidney application.

HYPOTHESIS: Graphene oxide (GO)-doping in polyethersulfone hollow fiber membranes (PES HFMs) improves the biocompatibility and separation performance for bioartificial kidney (BAK) application. EXPERIMENTS: GO was doped in PES HFMs. The physicochemical characterization of the developed HFMs was carried out. The biocompatibility tests including hemocompatibility and cytotoxicity tests, and separation experiments including uremic toxins clearance were performed. FINDINGS: GO-doping resulted in low hemolysis (0.37 ±â€¯0.15%), prolonged coagulation times, and low SC5b-9 marker level (6.84 ±â€¯1.7 ng/mL), i.e., significantly improved hemocompatibility of GP HFMs. The monolayer attachment and improved proliferation of kidney cells on the outer surface of GP HFMs were achieved. GO-doping significantly enhanced the separation performance, i.e., high pure water permeability (154 ±â€¯3 mL/m2/h/mmHg) was measured, and similar solute rejection profile as that of the commercial dialyzer membranes was recorded. The clearance of urea, creatinine and phosphorous from the simulated blood was measured to be almost 1.6 to 3.3 times higher than that measured for the commercial membranes. Thus, these results indicated that the GO-doping remarkably improved the performance of the developed GP HFMs thereby making them a potential membrane material for the BAK application.

Development and evaluation of microwave-assisted and ultrasound-assisted methods based on a quick, easy, cheap, effective, rugged, and safe sample preparation approach for the determination of bisphenol analogues in serum and sediments.

Microwave- and ultrasound-assisted methods based on a quick, easy, cheap, effective, rugged, and safe sample preparation approach followed by high-performance liquid chromatography with tandem mass spectrometry were developed for the simultaneous determination of eight bisphenol analogues in serum and sediment. The developed methods provided satisfactory extraction efficiency for the energy provided by microwaves and ultrasound. Compositions of commercial sorbents (primary secondary amine, MgSO4 , octadecyl-modified silica, and graphitized carbon black) were evaluated. The ultrasound-assisted method was suited for serum using primary secondary amine, MgSO4 , and octadecyl-modified silica as sorbents and a mixture of hexane and ethyl acetate as extraction solvent. The microwave-assisted method worked better for sediment with tetrahydrofuran and methanol as solvents and primary secondary amine, MgSO4 , octadecyl-modified silica, and graphitized carbon black as sorbents. Other experimental parameters, such as extraction temperature and time, were also optimized. The inter- and intraday relative standard deviations ranged from 2.7 to 5.5%. The limits of detection were between 0.1 and 1.0 ng/mL for serum and between 0.1 and 0.5 ng/g dry weight for sediment. The proposed methods were successfully applied to seven sediment and 20 human serum samples. The results showed that the developed methods were practical for the analysis and biomonitoring of bisphenols in sera and sediment.

Performance comparison of dispersive solid-phase extraction and multiplug filtration cleanup methods for the determination of tefuryltrione in plant and environmental samples using UHPLC-MS/MS.

The detection frequencies of tefuryltrione, a new type of 4-hydroxyphenyl-pyruvate dioxygenase inhibitor herbicide, are rarely reported, probably because of the paucity of analytical methods. Herein, an effective and sensitive analytical method has been developed to detect tefuryltrione in vegetables (tomato and cucumber), cereals (rice and corn), soil, and water by ultra high performance liquid chromatography coupled with tandem mass spectrometry. Comparisons of the performances of dispersive solid-phase extraction and multiplug filtration cleanup methods were carried out for tefuryltrione in complex matrices. Extraction solvents and purification sorbents were further optimized for dispersive solid-phase extraction. Tefuryltrione was analyzed with electrospray ionization in the positive mode within 2.0 min. Mean recoveries for tefuryltrione were 75.4-108.9% with relative standard deviations less than 11.0% at three fortification levels (10, 100, 500 µg/kg) in the sample matrixes. Limits of quantification ranged from 0.70 to 5.12 µg/kg, and an excellent linearity (R2 ≥ 0.9902) was obtained for tefuryltrione at concentrations of 5-1000 µg/L. The results showed that the developed dispersive solid-phase extraction method could serve as an effective, sensitive, and robust method for routine monitoring of tefuryltrione residue in plants and environmental samples.

Ionic liquid based vortex assisted liquid-liquid microextraction combined with liquid chromatography mass spectrometry for the determination of bisphenols in thermal papers with the aid of response surface methodology.

A sensitive, rapid and efficient ionic liquid-based vortex assisted liquid-liquid microextraction (IL-VALLME) with Liquid Chromatography Mass spectrometry (LC-MS/MS) method is proposed for the determination of bisphenols in thermal paper. Extraction factors were systematically optimized by response surface methodology. Experimental factors showing significant effects on the analytical responses were evaluated using design of experiment. The limit of detection for Bisphenol-A (BPA) and Bisphenol-S (BPS) in thermal paper were 1.25 and 0.93µgkg-1 respectively. The dynamic linearity range for BPA was between 4 and 100µgkg-1 and the determination of coefficient (R2) was 0.996. The values of the same parameters were 3-100µgkg-1 and 0.998 for BPS. The extraction recoveries of BPA and BPS in thermal paper were 101% and 99%. Percent relative standard deviation (% RSD) for matrix effect and matrix match effects were not more than 10%, for both bisphenols. The proposed method uses a statistical approach for the analysis of bisphenols in environmental samples, and is easy, rapid, requires minimum organic solvents and efficient.

Unbound fraction of fluconazole and linezolid in human plasma as determined by ultrafiltration: Impact of membrane type.

Ultrafiltration is a rapid and convenient method to determine the free concentrations of drugs in plasma. Several ultrafiltration devices based on Eppendorf cups are commercially available, but are not validated for such use by the manufacturer. Plasma pH, temperature and relative centrifugal force as well as membrane type can influence the results. In the present work, we developed an ultrafiltration method in order to determine the free concentrations of linezolid or fluconazole, both neutral and moderately lipophilic antiinfective drugs for parenteral as well as oral administration, in plasma of patients. Whereas both substances behaved relatively insensitive in human plasma regarding variations in pH (7.0-8.5), temperature (5-37°C) or relative centrifugal force (1000-10.000xg), losses of linezolid were observed with the Nanosep Omega device due to adsorption onto the polyethersulfone membrane (unbound fraction 75% at 100mg/L and 45% at 0.1mg/L, respectively). No losses were observed with Vivacon which is equipped with a membrane of regenerated cellulose. With fluconazole no differences between Nanosep and Vivacon were observed. Applying standard conditions (pH 7.4/37°C/1000xg/20min), the mean unbound fraction of linezolid in pooled plasma from healthy volunteers was 81.5±2.8% using Vivacon, that of fluconazole was 87.9±3.5% using Nanosep or 89.4±3.3% using Vivacon. The unbound fraction of linezolid was 85.4±3.7% in plasma samples from surgical patients and 92.1±6.2% in ICU patients, respectively. The unbound fraction of fluconazole was 93.9±3.3% in plasma samples from ICU patients.

Application of Orbitrap-mass spectrometry to differentiate isomeric sildenafil- and thiosildenafil-like analogues used for the adulteration of dietary supplements.

Two groups of isomeric phosphodiestrase-type 5 inhibitors (PDE-5), consisting of four sildenafil- and three thiosildenafil-like analogues, have been successfully differentiated using high-resolution MS/MS. The optimised MS/MS data obtained from each compound were used to build a database with the aid of mass processing software. Isomeric compounds with very close chromatographic separation like dimethylsildenafil and homosildenafil could be distinguished by their unique fingerprint fragment ions in the MS/MS database. All fragment ions were within the mass tolerance of 5 ppm. One case study using an adulterated dietary supplement is included to provide more insights into this application.

Entre o campo e o laboratório: a dinâmica de produção de conhecimento no Ambulatório de Menopausa do Caism/Unicamp / Between the country and the laboratory: the dynamics of the production of knowledge at the Menopause Outpatients Clinic at Caism, Unicamp

Este estudo investiga as práticas de produção de conhecimento sobre a menopausa no Caism/Unicamp, centro de referência para políticas públicas em saúde da mulher. Foram realizadas observações de consultas ginecológicas, entrevistas com mulheres e médicos e observação de reuniões de apoio psicológico, buscando identificar os discursos que circulam no lugar e o processo de alistamento de diferentes atores para que os conhecimentos ali produzidos alcancem credibilidade e “viajem” além dos limites do hospital-escola, tornando-se “universais”. A análise baseia-se nos “estudos localistas”, alinhados aos estudos sociais de ciência e tecnologia.

This study investigates the practices involved in the production of knowledge about menopause at Caism, Unicamp, a reference center for public policies for women’s health. Gynecological appointments and psychological support meetings were observed, and women and doctors were interviewed in order to identify what discourse circulates there and how different actors are brought in to ensure that the knowledge produced attains credibility and “travels” beyond the boundaries of the teaching hospital to become “universal”. The analysis is based on localized studies aligned with social studies of science and technology.

Asterisulphoxide and asterisulphone: two new antibacterial and antifungal metabolites from the Tunisian Asteriscus maritimus (L.) Less.

Two new sulphur-containing metabolites, asterisulphoxide 1 and asterisulphone 2, together with six known compounds, coniferaldehyde 4, 4-hydroxy-2-methoxybenzaldehyde 3, methylcaffeate 5, isobutyrate 10-isobutyryloxy-8,9-epoxythymyle 6, 8,9-dihydroxy-10-isobutyryloxythymol 7 and 8-hydroxy-9,14-diisobutyryloxythymol 8, were isolated from Asteriscus maritimus roots. Their structures were elucidated on the basis of spectroscopic evidence and comparison with authentic samples. Compounds 1-8 were assessed for their in vitro antibacterial activity against Pseudomonas aureofasciens, Burkholderia glathei, Bacillus pumilus and their antifungal effects against Aspergillus flavus, Aspergillus niger, Penicillium digitatum, Botrytis cinerea and Fusarium oxysporum f. sp. lycopersici, using the disc diffusion method (20 µL/disc). A remarkable inhibition zone 10-15 mm of the growth of the bacterial and fungal agents was observed. The obtained results suggest that the isolated compounds could be promising abiotic antimicrobial agents.

Simultaneous identification of 18 illegal adulterants in dietary supplements by using high-performance liquid chromatography-mass spectrometry.

We developed a method for the identification of 18 illegal adulterants in dietary supplements for erectile dysfunction by using high-performance liquid chromatography-mass spectrometry. The separation was achieved on a Cosmosil 3C18-EB column. The mobile phase consisted of 0.1% formic acid solution and 0.1% formic acid in acetonitrile, with gradient elution at a flow rate of 0.15 mL/min. The proposed method may be useful for the identification of illegal adulterants and for quality control of dietary supplements.

[Analysis and identification of illegal constituents in health food products implicitly advertizing tonic or slimming effect in the National Institute of Health Sciences in Japan].

With the prefectural governments' aid of the purchase, the Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences (NIHS) successively has surveyed illegal constituents in health food products implicitly advertizing tonic or slimming effect since the fiscal year of 2002 (slimming type) or 2003 (tonic type). The average numbers of the analyzed products per year are about 100 (slimming type) and 150 (tonic type), respectively. We also continuously distribute standards of authentic samples of several illegal components such as N-nitrosofenfluramine (NFF) and sildenafil (SIL) to prefectural institutes and the average gross number per year is about 140. In the case of slimming type, the fact that the products containing NFF were widely sold in Japanese markets in 2002 is well known. In addition, phenolphthalein, fenfluramine, sibtramine, desdimethylsibtramine, orlistat, mazindol, Rhubarb, Senna Leaf, etc. have been found as illegal constituents. In the tonic type products, we have identified more than 20 synthetic compounds relating to the erectile dysfunction (ED) treatment drugs, SIL, vardenafil and tadalafil (TDF). Since 2005, their synthetic intermediates and the patented but non-approved PDE5 inhibitors also have been found. It should be noted that TDF was found in the shells of capsule in 2009 and that mutaprodenafil was found as pro-drug type illegal component in 2010. In this report identification method of these illegal constituents is briefly described and then analytical trend in this decade is reviewed.

Isolation and identification of novel propoxyphenyl thiosildenafil found in natural health food product.

A novel phosphodiesterase-5 (PDE-5) inhibitor was found in a natural health food product. The previously unknown sildenafil analogue was isolated using preparative HPLC. The structure of the compound was elucidated using HPLC with diode array detection (DAD), time-of-flight mass spectrometry (TOF/MS), and nuclear magnetic resonance spectroscopy (NMR). An [M + H](+) ion was detected at m/z 505.2077 by LC-TOF/MS that was consistent with C23H32N6O3S2 (-0.98 ppm). By NMR analysis, the analogue was identified as 1-methyl-5-(5-(4-methylpiperazin-1-ylsulfonyl)-2-propoxyphenyl)-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-7(6H)-thione. In this structure, the ethoxy group of thiosildenafil was substituted by a propoxy group of the unknown compound. Therefore, this novel thiosildenafil analogue was named propoxyphenyl thiosildenafil.

Magnetic molecularly imprinted polymer for the selective extraction of sildenafil, vardenafil and their analogs from herbal medicines.

The successfully developed magnetic molecularly imprinted polymers (MMIPs) toward six synthetic phosphodiesterase type-5 (PDE-5) inhibitors were described. Sildenafil was used as template for the preparation of MMIPs using superparamagnetic core-shell nanoparticle as supporter. The obtained MMIPs were characterized using transmission electron microscope, Fourier transform infrared, X-ray diffraction, and vibrating sample magnetometer. High performance liquid chromatography (HPLC) with diode array detector (DAD) was used for the analysis of target analytes. The application of MMIPs as selective sorbent in the cleanup of herbal medicine samples prior to HPLC offered simple sample preparation. The adsorption capacity and selectivity of prepared MMIPs and magnetic non-molecularly imprinted polymers were investigated. The binding isotherms were obtained for sildenafil and fitted by Freundlich isotherm model. Structurally similar compound of sildenafil and a reference compound protocatechuic acid were used for investing the selective recognition of MMIPs.

Simultaneous identification of hydroxythiohomosildenafil, aminotadalafil, thiosildenafil, dimethylsildenafil, and thiodimethylsildenafil in dietary supplements using high-performance liquid chromatography-mass spectrometry.

We developed a method for the separation and identification of illegal adulterants (hydroxythiohomosildenafil, aminotadalafil, thiosildenafil, dimethylsildenafil, and thiodimethylsildenafil) from dietary supplements using high-performance liquid chromatography-mass spectrometry. The separation was achieved on a C18 column: the mobile phase consisted of 5 mM ammonium formate (pH 6.3)-acetonitrile (75 : 25, v/v) and acetonitrile, with gradient elution at a flow rate of 0.2 mL/min. The proposed method could also be used to separate vardenafil, homosildenafil, and dimethylsildenafil, all of which have the same molecular weight. Furthermore, the proposed method could simultaneously separate hydroxythiohomosildenafil, aminotadalafil, thiosildenafil, dimethylsildenafil, thiodimethylsildenafil, vardenafil, and homosildenafil. Thus, this method may be useful to identify medicinal ingredients for erectile dysfunction and their analogs and to control the quality of dietary supplements.

Determination of sildenafil, vardenafil and aildenafil in human plasma by dispersive liquid-liquid microextraction-back extraction based on ionic liquid and high performance liquid chromatography-ultraviolet detection.

A novel method which involved dispersive liquid-liquid microextraction (DLLME)-back extraction based on ionic liquid (IL) was developed for the determination of three phosphodiesterase-5 (PDE-5) inhibitors, sildenafil (SD), vardenafil (VD) and aildenafil (AD), in human plasma. DLLME based on IL as the extractant solvent and methanol as the dispersive solvent was the first step to extract PDE-5 inhibitors from sample solution; the other step of back extraction was followed by transferring target analytes from the IL to acidified aqueous solution. This two-step extraction ensured the compatibility of the final extractant phase, acidified aqueous solution herein, with the reversed phase high performance liquid chromatography-UV detection, and afforded clean extractant phase. The optimal extraction condition was obtained after systematical optimization. The sample solution (960µL) was extracted by 20µL of 1-octyl-3-methylimidazolium hexafluorophosphate in the presence of 20µL methanol and 300mgmL(-1) NaCl with the assistance of vortex; IL phase enriched with the target analytes was then extracted by 10% acetic acid aqueous solution. Good linearity ranges (SD 1-500ngmL(-1), VD 2-2000ngmL(-1) and AD 2-2000ngmL(-1)) with suitable r(2) (=0.9999) were achieved. Limits of detection (LODs) in pure water were 0.15ngmL(-1), 0.30ngmL(-1) and 0.43ngmL(-1) for VD, SD and AD, respectively. Intra-day and inter-day relative standard deviations were below 6.38%. Finally, this method was applied for the determination of PDE-5 inhibitors in human plasma with satisfactory LODs of 0.92ngmL(-1), 1.19ngmL(-1) and 2.69ngmL(-1) for VD, SD and AD, respectively. Acceptable absolute recoveries were obtained from 100.4% to 103.9%. The developed method afforded a convenient, fast and cost-saving operation with high extraction efficiency for the test analytes. It has potential to be applicable to biological samples.

Isolation and structural elucidation of a new sildenafil analogue from a functional coffee.

A sildenafil analogue was detected in a functional coffee sample labelled to have male sexual performance enhancement effects. This analogue was isolated and purified by flash chromatography and preparative high-performance liquid chromatography. Its structure was elucidated using high-resolution mass spectrometry; electrospray ionization-tandem mass spectrometry; and nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, and infrared spectroscopy. Compared with sildenafil, instead of an N-methylpiperazinyl moiety, ring opening of the piperazine ring with the loss of a carbon atom resulted in a substituted benzenesulfonamide. The chemical name of this analogue is N-[2-(dimethylamino)ethyl]-4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide. It is named descarbonsildenafil because it has one less carbon atom when compared with sildenafil.