title: Safety and efficacy of new 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine analogs as potential phosphodiesterase-4 inhibitors in NIH-3T3 mouse fibroblastic cells.
abstract: A novel series of potential phosphodiesterase-4 (PDE-4) inhibitors, 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-aryl-7H-[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.
authors: Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Maryam
authors: M
authors: Baeeri
authors: Alireza
authors: A
authors: Foroumadi
authors: Maryam
authors: M
authors: Motamedi
authors: Azadeh
authors: A
authors: Yahya-Meymandi
authors: Loghman
authors: L
authors: Firoozpour
authors: Seyed N
authors: SN
authors: Ostad
authors: Abbas
authors: A
authors: Shafiee
authors: Saeid
authors: S
authors: Souzangarzadeh
authors: Mohammad
authors: M
authors: Abdollahi
mesh_terms: D000818:Animals; D002470:Cell Survival; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology; D013829:Thiadiazines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D013829:Thiadiazines; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006152:Cyclic GMP; D020889:Rolipram