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Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Bottom Line: Phosphodiesterase 4B has constituted an interesting target for drug development.In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents.In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, J. S. S. College of Pharmacy, Ootacamund-643001, Tamil Nadu, India.

ABSTRACT
Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of proteins that plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) by controlling its rate of degradation. It has been demonstrated that this isoform is involved in the orchestra of events which includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary disease, contractility of the myocardium, and psoriatic arthritis. Phosphodiesterase 4B has constituted an interesting target for drug development. In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents. In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

No MeSH data available.


Related in: MedlinePlus

Structure of 1,2-dihydroquinolinemethanesulfonamide analogues that have shown potent PDE4B inhibition and anticancer activity
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Figure 23: Structure of 1,2-dihydroquinolinemethanesulfonamide analogues that have shown potent PDE4B inhibition and anticancer activity

Mentions: In the year 2013, novel N-[(1-substituted-1H-1,2,3-triazol-4-yl)methyl]-N-2,2,4-trimethyl-7-phenoxy-1,2-dihydroquinolinemethanesulfonamides 48a–e (Figure 23) were synthesized as selective PDE4B inhibitors. The reaction was carried out in aqueous DMF via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as the key step [66]. The compounds were evaluated in vitro for their cytotoxic activity using the lung adenocarcinoma epithelial cell line (A549), prostate cancer cell line (DU145), cervical cancer cell line (HeLa), and hepatocellular liver carcinoma cell line (HepG2) in an MTT assay. Among the synthesized inhibitors, 48a and 48b showed promising activity against the human lung cancer cell line (A549) with an IC50 of 8–9 µM. Although compounds 48b, 48d, and 48e were identified as potent PDE4B inhibitors, they showed no cytotoxic activity towards the tested cancer cell lines. The docking results of the synthesized compounds revealed a high binding affinity of compound 48d with 1XMY (PBD ID). Hydrogen bonding with HIE-234 and π-π stacking interactions with PHE446 residues were also observed.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Structure of 1,2-dihydroquinolinemethanesulfonamide analogues that have shown potent PDE4B inhibition and anticancer activity
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318138&req=5

Figure 23: Structure of 1,2-dihydroquinolinemethanesulfonamide analogues that have shown potent PDE4B inhibition and anticancer activity
Mentions: In the year 2013, novel N-[(1-substituted-1H-1,2,3-triazol-4-yl)methyl]-N-2,2,4-trimethyl-7-phenoxy-1,2-dihydroquinolinemethanesulfonamides 48a–e (Figure 23) were synthesized as selective PDE4B inhibitors. The reaction was carried out in aqueous DMF via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as the key step [66]. The compounds were evaluated in vitro for their cytotoxic activity using the lung adenocarcinoma epithelial cell line (A549), prostate cancer cell line (DU145), cervical cancer cell line (HeLa), and hepatocellular liver carcinoma cell line (HepG2) in an MTT assay. Among the synthesized inhibitors, 48a and 48b showed promising activity against the human lung cancer cell line (A549) with an IC50 of 8–9 µM. Although compounds 48b, 48d, and 48e were identified as potent PDE4B inhibitors, they showed no cytotoxic activity towards the tested cancer cell lines. The docking results of the synthesized compounds revealed a high binding affinity of compound 48d with 1XMY (PBD ID). Hydrogen bonding with HIE-234 and π-π stacking interactions with PHE446 residues were also observed.

Bottom Line: Phosphodiesterase 4B has constituted an interesting target for drug development.In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents.In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, J. S. S. College of Pharmacy, Ootacamund-643001, Tamil Nadu, India.

ABSTRACT
Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of proteins that plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) by controlling its rate of degradation. It has been demonstrated that this isoform is involved in the orchestra of events which includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary disease, contractility of the myocardium, and psoriatic arthritis. Phosphodiesterase 4B has constituted an interesting target for drug development. In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents. In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

No MeSH data available.


Related in: MedlinePlus