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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 1,2,4-triazole analogues that have PDE4B inhibition and anticancer activity
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Figure 24: Structure of 1,2,4-triazole analogues that have PDE4B inhibition and anticancer activity

Mentions: The novel nimesulide-based new class of triazole derivatives 49a–d (Figure 24) were synthesized as PDE4B inhibitors [67]. The synthesized compounds were tested against cancer cells, keeping in view the reported anticancer activity of nimesulide [68] and the anti-inflammatory activity of 1,2,4-triazoles [69]. Some of the synthesized compounds exhibited significant in vitro PDE4B inhibitory properties with >50% inhibition at 30 µM. Moreover, results were also supported by the docking studies. The in vitro anticancer activity was evaluated using the HCT-15 human colon cancer cell lines with doxorubicin [IC50 50 µg/mL, (0.09 µM)], an anthracyclin antibiotic as the reference compound. Two of the synthesized compounds 49c and 49d exhibited IC50 values in the range 21-22 µg/mL. Docking results of synthesized compounds revealed similar interactions with Gln443 as that of rolipram. Apart from Gln443, compound 49a also exhibited interactions with His234 and His278, whereas compound 49b and 49c showed binding affinity for Asn283.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Structure of 1,2,4-triazole analogues that have PDE4B inhibition and anticancer activity
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 24: Structure of 1,2,4-triazole analogues that have PDE4B inhibition and anticancer activity
Mentions: The novel nimesulide-based new class of triazole derivatives 49a–d (Figure 24) were synthesized as PDE4B inhibitors [67]. The synthesized compounds were tested against cancer cells, keeping in view the reported anticancer activity of nimesulide [68] and the anti-inflammatory activity of 1,2,4-triazoles [69]. Some of the synthesized compounds exhibited significant in vitro PDE4B inhibitory properties with >50% inhibition at 30 µM. Moreover, results were also supported by the docking studies. The in vitro anticancer activity was evaluated using the HCT-15 human colon cancer cell lines with doxorubicin [IC50 50 µg/mL, (0.09 µM)], an anthracyclin antibiotic as the reference compound. Two of the synthesized compounds 49c and 49d exhibited IC50 values in the range 21-22 µg/mL. Docking results of synthesized compounds revealed similar interactions with Gln443 as that of rolipram. Apart from Gln443, compound 49a also exhibited interactions with His234 and His278, whereas compound 49b and 49c showed binding affinity for Asn283.

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