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Safety and Efficacy of New 3,6‐diaryl‐7 H ‐[1,2,4]triazolo[3,4‐ b ][1,3,4]thiadiazine Analogs as Potential Phosphodiesterase‐4 Inhibitors in NIH‐3T3 Mouse Fibroblastic Cells
Author(s) -
Baeeri Maryam,
Foroumadi Alireza,
Motamedi Maryam,
YahyaMeymandi Azadeh,
Firoozpour Loghman,
Ostad Seyed N.,
Shafiee Abbas,
Souzangarzadeh Saeid,
Abdollahi Mohammad
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01167.x
Subject(s) - phosphodiesterase , rolipram , cyclic guanosine monophosphate , guanosine , chemistry , cyclic adenosine monophosphate , enzyme , in vitro , adenosine , mtt assay , stereochemistry , pharmacology , biochemistry , biology , receptor , organic chemistry , nitric oxide
A novel series of potential phosphodiesterase‐4 (PDE‐4) inhibitors, 6‐(3‐(cyclopentyloxy)‐4‐methoxyphenyl)‐3‐aryl‐7 H ‐[1,2,4]triazolo[3,4‐ b ][1,3,4]thiadiazines, were developed. Different concentrations of the synthesized compounds were tested on cultured NIH‐3T3 cells to determine their safety and efficacy in NIH‐3T3 mouse fibroblastic cells in comparison with rolipram, a selective PDE‐4 inhibitor. The viability of cells was determined by (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐di‐phenyltetrazoliumbromide (MTT) assay. The PDE inhibition rate was measured indirectly by determination of concentrations of extracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) using enzyme‐linked immunoassay technique. The results showed that all tested compounds caused a marked increase in the concentration of cAMP, whereas the concentration of cGMP stayed approximately unchanged. The cytotoxic IC 50 of all synthesized compounds was approximately twofold greater than their required concentration for inhibition of PDE‐4 (in terms of elevation of cAMP), and thus, these structures could be used to develop potent and safe inhibitors of PDE‐4 enzyme.