Design, synthesis, and biological evaluation of some new 2-phenyl-3,6-pyridazinedione derivatives as PDE-5 inhibitors
Bioorg Chem. 2024 Feb 16;145:107213. doi: 10.1016/j.bioorg.2024.107213. Online ahead of print.ABSTRACTVarious 2-phenyl-3,6-pyridazinedione derivatives 4a-j, 5a-c, 6a,b, 7a-c, 8, 9, 10a-d, and 11a-d, were effectivelysynthesized, and tested for their potential inhibition of phosphodiesterase enzyme at 10 µM. Then fourteen compounds exhibiting the highest inhibition 4b, 4d, 4e, 4g, 4h, 4i, 5a, 6a,b, 7c, 10a,b, 11a, and 11d were selected for screening their PDE-5 inhibition, where compounds 4b,g,h, and 11a revealed promising PDE-5 inhibition having IC50 values = 25, 53, 22, and 42 nM, respectively in comparison with Sildenafi...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Zeinab S Abd-Rabo Riham F George Dalia K Zaafar Aya Y Gawish Aya M Serry Source Type: research
Design, synthesis, and biological evaluation of some new 2-phenyl-3,6-pyridazinedione derivatives as PDE-5 inhibitors
Bioorg Chem. 2024 Feb 16;145:107213. doi: 10.1016/j.bioorg.2024.107213. Online ahead of print.ABSTRACTVarious 2-phenyl-3,6-pyridazinedione derivatives 4a-j, 5a-c, 6a,b, 7a-c, 8, 9, 10a-d, and 11a-d, were effectivelysynthesized, and tested for their potential inhibition of phosphodiesterase enzyme at 10 µM. Then fourteen compounds exhibiting the highest inhibition 4b, 4d, 4e, 4g, 4h, 4i, 5a, 6a,b, 7c, 10a,b, 11a, and 11d were selected for screening their PDE-5 inhibition, where compounds 4b,g,h, and 11a revealed promising PDE-5 inhibition having IC50 values = 25, 53, 22, and 42 nM, respectively in comparison with Sildenafi...
Source: Bioorganic Chemistry - February 18, 2024 Category: Chemistry Authors: Zeinab S Abd-Rabo Riham F George Dalia K Zaafar Aya Y Gawish Aya M Serry Source Type: research
Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response
ConclusionsOur results indicate that the changes in cGMP and purine pools, as well as mitochondrial function which is observed upon PDE6 γ′ depletion, are independent of the PKG pathway. We show that in HCT116,PDE6H deletion replicates many effects of the dark retina response and identifyPDE6H as a new target in preventing cancer cell proliferation and tumour growth. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - February 13, 2024 Category: Cancer & Oncology Source Type: research
Inhibition of PDE ‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions
AbstractThe aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre-contracted with 5-HT (100 μM). Upon generation of stable phasic contractions, PDE-4 and PDE-5 inhibitors were added cumulatively to separate tissues. PDE-4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, whil e a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressan...
Source: Pharmacology Research and Perspectives - February 11, 2024 Category: Drugs & Pharmacology Authors: Iris Lim,
Taishi Masutani,
Hikaru Hashitani,
Russ Chess ‐Williams,
Donna Sellers Tags: ORIGINAL ARTICLE Source Type: research
Efficient administration of a combination of nifedipine and sildenafil citrate versus only nifedipine on clinical outcomes in women with threatened preterm labor: a systematic review and meta-analysis
Preterm labor (PTL) is a common and serious pregnancy disorder that can cause long-term neurological issues in the infant. There are conflicting studies concerning whether sildenafil citrate (SC) reduces prete... (Source: BMC Pediatrics)
Source: BMC Pediatrics - February 10, 2024 Category: Pediatrics Authors: Elham Manouchehri, Somayeh Makvandi, Mahdieh Razi, Maryam Sahebari and Mona Larki Tags: Research Source Type: research
Does Viagra ward off Alzheimer's disease? It's too soon to say
A new study has found an intriguing link between erectile dysfunction drugs and lower Alzheimer ' s risk, but they are not definitive (Source: New Scientist - Health)
Source: New Scientist - Health - February 8, 2024 Category: Consumer Health News Source Type: research
GSE254742 Sildenafil as a candidate drug for Alzheimer ’s disease: Real-world patient data observation and mechanistic observations from patient-induced pluripotent stem cell-derived neurons.
Contributors : Dhruv Gohel ; Amit K Gupta ; Feixiong ChengSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAlzheimer ’s disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential beneficial effect in AD. We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced ...
Source: GEO: Gene Expression Omnibus - February 5, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells
Sci Signal. 2024 Jan 30;17(821):eadi7861. doi: 10.1126/scisignal.adi7861. Epub 2024 Jan 30.ABSTRACTAndrogen binding to the androgen receptor (AR) in the cytoplasm induces the AR to translocate to the nucleus, where it regulates the expression of target genes. Here, we found that androgens rapidly activated a plasma membrane-associated signaling node that enhanced nuclear AR functions. In murine primary osteoblasts, dihydrotestosterone (DHT) binding to a membrane-associated form of AR stimulated plasma membrane-associated protein kinase G type 2 (PKG2), leading to the activation of multiple kinases, including ERK. Phosphory...
Source: Science Signaling - January 30, 2024 Category: Biomedical Science Authors: Hema Kalyanaraman Darren E Casteel Shyamsundar Pal China Shunhui Zhuang Gerry R Boss Renate B Pilz Source Type: research
The impact of phosphodiesterase ‐5 inhibition or angiotensin‐converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload
Despite elevated cGMP levels in the lungs of sildenafil-treated rats, PDE5i did not improve survival rate and did not change the cardiac and renal function of ACF rats with advanced HF. In contrast, mortality in the ACF model was reduced by ACEi treatment. AbstractWhile phosphodiesterase-5 inhibition (PED5i) may prevent hypertrophy and failure in pressure-overloaded heart in an experimental model, the impact of PDE5i on volume-overload (VO)-induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long-term PDE5i and if this t...
Source: Pharmacology Research and Perspectives - January 29, 2024 Category: Drugs & Pharmacology Authors: Tereza Tykvartova,
Matus Miklovic,
Martin Kotrc,
Petra Skaroupkova,
Ludmila Kazdova,
Jaroslava Trnovska,
Vojtech Skop,
Michal Kolar,
Jiri Novotny,
Vojtech Melenovsky Tags: ORIGINAL ARTICLE Source Type: research
Efficacy of Sildenafil on healthy humans in high ‑altitude hypoxia at rest and during exercise: A meta‑analysis
Exp Ther Med. 2024 Jan 8;27(2):88. doi: 10.3892/etm.2024.12376. eCollection 2024 Feb.ABSTRACTThe current meta-analysis aimed to fully evaluate the efficacy of Sildenafil in healthy humans at different altitudes, focusing on echocardiographic and hemodynamic parameters. Relevant studies were retrieved from the Cochrane, Embase and PubMed databases. Odds ratios (OR) were determined for dichotomous data and weighted mean differences with 95% confidence intervals (CIs) for continuous data. A total of 16 RCTs were included in the current meta-analysis. Short-term treatment with Sildenafil significantly elevated resting heart ra...
Source: Experimental and Therapeutic Medicine - January 26, 2024 Category: General Medicine Authors: Zhan-Cui Dang Zhiquan Yang Shou Liu Guo-Mei Du Linde Jin Zhong-Zhi Zhao Source Type: research
Pressure overload is associated with right ventricular dyssynchrony in heart failure with reduced ejection fraction
ConclusionsRV dyssynchrony is associated with RV remodelling, dysfunction, adverse haemodynamics, and greater risk for adverse clinical events. RV dyssynchrony is mitigated by acute RV afterload reduction and could be a potential therapeutic target to improve RV performance in HFrEF. (Source: ESC Heart Failure)
Source: ESC Heart Failure - January 24, 2024 Category: Cardiology Authors: Luca Monzo,
Marek Tupy,
Barry A. Borlaug,
Adrian Reichenbach,
Ivana Jurcova,
Jan Benes,
Lenka Mlateckova,
Jiri Ters,
Josef Kautzner,
Vojtech Melenovsky Tags: Original Article Source Type: research
Unravelling the role of Sildenafil and SB204741 in suppressing fibrotic potential of peritoneal fibroblasts obtained from PD patients
Discussion: Taken together, the above research evidences that the combination of sildenafil and SB204741 may have therapeutic potential in suppressing peritoneal fibrosis due to peritoneal dialysis. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 23, 2024 Category: Drugs & Pharmacology Source Type: research
Synergistic effect of sildenafil combined with controlled hypothermia to alleviate microglial activation after neonatal hypoxia –ischemia in rats
The only validated treatment to prevent brain damage associated with hypoxia –ischemia (HI) encephalopathy of the newborn is controlled hypothermia with limited benefits. Additional putative neuroprotective dru... (Source: Journal of Neuroinflammation)
Source: Journal of Neuroinflammation - January 23, 2024 Category: Neurology Authors: Pansiot Julien, Manuela Zinni, Natacha Bonnel, Marina El Kamouh, Felipe Odorcyk, Lea Peters, Emilie-Fleur Gautier, Marjorie Leduc, C édric Broussard and Olivier Baud Tags: Research Source Type: research
