First molecular modelling report on tri-substituted pyrazolines as phosphodiesterase 5 (PDE5) inhibitors through classical and machine learning based multi-QSAR analysis

2021 ◽  
pp. 1-23
Author(s):  
S. Nandi ◽  
P. Kumar ◽  
S.A. Amin ◽  
T. Jha ◽  
S. Gayen
Keyword(s):  
Machine Learning ◽  
Molecular Modelling ◽  
Pde5 Inhibitors ◽  
Qsar Analysis ◽  
Phosphodiesterase 5

The Effect of PDE5 Inhibitors on the Male Reproductive Tract

2020 ◽  
Vol 26 ◽  
Author(s):  
Nikolaos Sofikitis ◽  
Aris Kaltsas ◽  
Fotios Dimitriadis ◽  
Jens Rassweiler ◽  
Nikolaos Grivas ◽  
...  
Keyword(s):  
Male Infertility ◽  
Reproductive Tract ◽  
Tunica Albuginea ◽  
Scientific Data ◽  
Secretory Function ◽  
Pde5 Inhibitors ◽  
Male Reproductive Tract ◽  
Review Study ◽  
Phosphodiesterase 5

The therapeutic range of cyclic nucleotide phosphodiesterase 5 inhibitors (PDE5) inhibitors is getting wider in the last years. This review study focuses on the potential employment of PDE5 inhibitors as an adjunct tool for the therapeutic management of male infertility. The literature tends to suggest a beneficial effect of PDE5 inhibitors on Leydig and Sertoli cells secretory function. It also appears that PDE5 inhibitors play a role in the regulation of the contractility of the testicular tunica albuginea and the epididymis. Moreover scientific data suggest that PDE5 inhibitors enhance the prostatic secretory function leading to an improvement in sperm motility. Other studies additionally demonstrate a role of PDE5 inhibitors in the regulation of sperm capacitation process. Placebo-controlled, randomized, blind studies are necessary to unambiguously incorporate PDE5 inhibitors as an adjunct tool for the pharmaceutical treatment of semen disorders and male infertility.

Applications of Quantitative Structure-Activity Relationships (QSAR) based Virtual Screening in Drug Design: A Review

2020 ◽  
Vol 20 (14) ◽  
pp. 1375-1388 ◽  
Author(s):  
Patnala Ganga Raju Achary
Keyword(s):  
Machine Learning ◽  
Drug Discovery ◽  
Virtual Screening ◽  
Model Building ◽  
Chemical Space ◽  
Qsar Model ◽  
Quantitative Structure ◽  
Efficient Manner ◽  
Qsar Analysis ◽  
Structure Activity

The scientists, and the researchers around the globe generate tremendous amount of information everyday; for instance, so far more than 74 million molecules are registered in Chemical Abstract Services. According to a recent study, at present we have around 1060 molecules, which are classified as new drug-like molecules. The library of such molecules is now considered as ‘dark chemical space’ or ‘dark chemistry.’ Now, in order to explore such hidden molecules scientifically, a good number of live and updated databases (protein, cell, tissues, structure, drugs, etc.) are available today. The synchronization of the three different sciences: ‘genomics’, proteomics and ‘in-silico simulation’ will revolutionize the process of drug discovery. The screening of a sizable number of drugs like molecules is a challenge and it must be treated in an efficient manner. Virtual screening (VS) is an important computational tool in the drug discovery process; however, experimental verification of the drugs also equally important for the drug development process. The quantitative structure-activity relationship (QSAR) analysis is one of the machine learning technique, which is extensively used in VS techniques. QSAR is well-known for its high and fast throughput screening with a satisfactory hit rate. The QSAR model building involves (i) chemo-genomics data collection from a database or literature (ii) Calculation of right descriptors from molecular representation (iii) establishing a relationship (model) between biological activity and the selected descriptors (iv) application of QSAR model to predict the biological property for the molecules. All the hits obtained by the VS technique needs to be experimentally verified. The present mini-review highlights: the web-based machine learning tools, the role of QSAR in VS techniques, successful applications of QSAR based VS leading to the drug discovery and advantages and challenges of QSAR.

ChemInform Abstract: 1-(2-Ethoxyethyl)-1H-pyrazolo[4,3-d]pyrimidines as Potent Phosphodiesterase 5 (PDE5) Inhibitors.

ChemInform ◽  
2010 ◽  
Vol 41 (43) ◽  
pp. no-no
Author(s):  
Michael B. Tollefson ◽  
Brad A. Acker ◽  
E. J. Jacobsen ◽  
Robert O. Hughes ◽  
John K. Walker ◽  
...  
Keyword(s):  
Pde5 Inhibitors ◽  
Phosphodiesterase 5

Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors

2020 ◽  
Vol 28 (18) ◽  
pp. 115657
Author(s):  
Aladdin M. Srour ◽  
Nesreen S. Ahmed ◽  
Somaia S. Abd El-Karim ◽  
Manal M. Anwar ◽  
Salwa M. El-Hallouty
Keyword(s):  
Molecular Modelling ◽  
Biological Evaluation ◽  
Egfr Inhibitors ◽  
Design Synthesis ◽  
Qsar Analysis

scholarly journals Liposomal Delivery of a Phosphodiesterase 5 Inhibitor Enhances Prostacyclin-Mediated Adenosine Triphosphate Release from Human Red Blood Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4803-4803
Author(s):  
Elizabeth Bowles ◽  
Randy Sprague ◽  
Nuran Ercal
Keyword(s):  
Side Effects ◽  
Red Blood Cells ◽  
Adenosine Triphosphate ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
Pde5 Inhibitor ◽  
Atp Release ◽  
Pde5 Inhibitors ◽  
Phosphodiesterase 5 ◽  
Human Rbcs

Abstract Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance (PVR) and right heart failure. Red blood cells (RBCs) of PAH patients fail to release the vasodilator, adenosine triphosphate (ATP), when deformed as would occur when traversing the lung. Such a defect could contribute to increased PVR. However, RBCs of PAH patients do release ATP in response to prostacyclin (PGI2) analogs and this is augmented by phosphodiesterase 5 (PDE5) inhibitors. Current PAH treatment includes PGI2 analogs and PDE5 inhibitors alone or in combination. Unfortunately, these drugs can have untoward side effects. Encapsulation of drugs within liposomes (small lipid-membraned vesicles) that can be targeted to RBCs has been shown to increase effectiveness and tolerability of some medications. The objective of this study was to determine if encapsulation of the PDE5 inhibitor zaprinast (ZAP) within liposomes is an effective means to deliver this class of drugs to human RBCs and if this approach would augment ATP release stimulated by the PGI2 analog UT-15c. Human RBCs were isolated and incubated with either blank liposomes (n=10), liposomes containing ZAP (n=9) or liposomes containing the PDE3 inhibitor, cilosatzol (CILO, n=10). RBCs (20% hematocrit) were then treated with UT-15c (1 µM). ATP release was measured before and 5, 10, and 15 min after the addition of UT-15c. In the presence of empty liposomes, the dose of UT-15c used did not stimulate ATP release. However, UT-15c did stimulate ATP release from RBCs pretreated with ZAP encapsulated by liposomes (P<0.01). The average time for maximal release was 9 ± 1 min. In contrast, when exposed to liposomes containing CILO, there was no ATP release following UT-15c administration. These studies demonstrate that the selective delivery of a PDE5 inhibitor to human RBCs potentiates UT-15c induced ATP release. Moreover the findings are consistent with the hypothesis that directed delivery of this class of drugs to PAH RBCs could be a new and important method to augment PGI2 analog-induced ATP release from these cells. Such an approach could significantly limit side effects of both drugs without compromise of their therapeutic effectiveness in PAH. Disclosures No relevant conflicts of interest to declare.

scholarly journals Molecular modelling guided design, synthesis and QSAR analysis of new small molecule non-lipid autotaxin inhibitors

2020 ◽  
Vol 103 ◽  
pp. 104188
Author(s):  
Souvik Banerjee ◽  
Derek D. Norman ◽  
Shanshan Deng ◽  
Sayo O. Fakayode ◽  
Sue Chin Lee ◽  
...  
Keyword(s):  
Small Molecule ◽  
Molecular Modelling ◽  
Design Synthesis ◽  
Qsar Analysis

Molecular modelling and QSAR analysis of the estrogenic activity of terpenoids isolated fromFerulaplants

2007 ◽  
Vol 18 (7-8) ◽  
pp. 663-673 ◽  
Author(s):  
B. F. Rasulev ◽  
A. I. Saidkhodzhaev ◽  
S. S. Nazrullaev ◽  
K. S. Akhmedkhodzhaeva ◽  
Z. A. Khushbaktova ◽  
...  
Keyword(s):  
Molecular Modelling ◽  
Estrogenic Activity ◽  
Qsar Analysis

scholarly journals Phenanthrenes from Eulophia macrobulbon as Novel Phosphodiesterase-5 Inhibitors

2017 ◽  
Vol 12 (1) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Prapapan Temkitthawon ◽  
Kanokwan Changwichit ◽  
Nantaka Khorana ◽  
Jarupa Viyoch ◽  
Khanit Suwanborirux ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Erectile Dysfunction ◽  
Chemical Constituents ◽  
Pde5 Inhibitor ◽  
Pde5 Inhibitors ◽  
New Class ◽  
Phosphodiesterase 5 Inhibitors ◽  
Phosphodiesterase 5

Phosphodiesterase 5 (PDE5) inhibitors can be used for the treatment of erectile dysfunction and pulmonary hypertension. In order to search for new leads of PDE5 inhibitors, we investigated the chemical constituents of the tubers of Eulophia macrobulbon (E.C. Parish & Rchb. f) Hook. f A new phenanthrene, 9,10-dihydro-4-(4′-hydroxybenzyl)-2,5-dimethoxyphenanthrene-1,7-diol (1) and three known phenanthrenes i.e., 1-(4′-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (2), (9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol (3) and 1,5,7-trimethoxyphenanthrene-2,6-diol) (4) were isolated. Among these, 2 was the most potent PDE5 inhibitor (IC50 =1.67±0.54 μM) evaluated by the [3H]cGMP radioassay method, whereas 1 showed mild activity (IC50 = 62.3±3.3 μM). Their inhibitory selectivities against PDE5 over PDE6 were also studied. This study suggests phenanthrenes as a new class of PDE5 inhibitors.

Molecular modelling and quantitative structure-activity relationship studies of anatoxin-a and epibatidine derivatives with affinity to rodent nAChR receptors

2014 ◽  
Vol 68 (8) ◽  
Author(s):  
Eduardo Melo ◽  
Sidnei Moura e Silva ◽  
Fávero Paula
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Molecular Modelling ◽  
Acetylcholine Receptors ◽  
Cognitive Disorders ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Biological Properties ◽  
Therapeutic Agents ◽  
Qsar Analysis ◽  
Parkinson’S Diseases

AbstractAnatoxin-a and epibatidine are natural toxins with a high affinity to nicotinic acetylcholine receptors (nAChR). Nicotinic ligands have the potential to become novel therapeutic agents for various cognitive disorders such as Alzheimer’s and Parkinson’s diseases. The determination of the physicochemical and biological properties of anatoxin-a and epibatidine derivatives is important because these might lead to the development of new cholinergic therapeutic agents. To study these features, the toxins and a set of their derivatives were subjected to a molecular modelling study and QSAR analysis. The structural analyses indicated that the geometric and steric features are important determinants of the compound’s activities. The descriptors selected for the QSAR model also highlighted the roles of the geometric and steric features, together with the importance of electronic features.

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