Design, synthesis and biological evaluation of some novel sulfonamide derivatives as apoptosis inducers

Mohamed K.O.; Nissan Y.M.; El-Malah A.A.; Ahmed W.A.; Ibrahim D.M.; Sakr T.M.; Motaleb M.A.

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Design, synthesis and biological evaluation of some novel sulfonamide derivatives as apoptosis inducers

Mohamed K.O.; Nissan Y.M.; El-Malah A.A.; Ahmed W.A.; Ibrahim D.M.; Sakr T.M.; Motaleb M.A.

Full Text link: https://t.ly/GgZxb

Date issued: 2017

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Doi: https://doi.org/10.1016/j.ejmech.2017.04.069 PubMed ID 28463785

Publisher: Elsevier Masson SAS

Series Info: European Journal of Medicinal Chemistry
135

Type: Article

Keywords: October University for Modern Sciences and Arts , جامعة أكتوبر للعلوم الحديثة والآداب , University of Modern Sciences and Arts , MSA University , Apoptosis , Caspase-3 , Fas-ligand , Radiolabeling , Technetium-99�m , Thiazolidinone , 4 [(3 phenylthiazolo[4,5 c]isoxazol 5 yl)amino]benzenesulfonamide , 4 [(5 benzylidene 4 oxo 4,5 dihydrothiazol 2 yl)amino]benzenesulfonamide , 4 [(5 oxo 7 phenyl 5,6 dihydrothiazolo[4,5 d]pyrimidin 2yl)amino]benzenesulfonam , 4 [(7 phenyl 5 thioxo 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl)amino]benzenesulfonamide , 4 [[3 (4 chlorophenyl)thiazolo[4,5 c]isoxazol 5 yl]amino]benzenesulfonamide , 4 [[3 (4 methoxyphenyl)thiazolo[4,5 c]isoxazol 5 yl]amino]benzenesulfonamide , 4 [[5 oxo 7 (4 chlorophenyl) 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl]amino]benzenesulfonamide , 4 [[5 oxo 7 (4 methoxyphenyl) 5,6 dihydrothiazolo[4,5-d]pyrimidin 2 yl]amino]benzenesulfonamide , 4 [[7 (4 chlorophenyl) 5 thioxo 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl]amino]benzenesulfonamide , 4 [[7 (4 methoxyphenyl) 5 thioxo 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl]amino]benzenesulfonamide , apoptosis inhibitor , caspase 3 , cytotoxic agent , doxorubicin , Fas ligand , fluorouracil , sulfonamide , technetium 99m , unclassified drug , sulfonamide , albino mouse , animal experiment , Article , Caco-2 cell line , controlled study , cytotoxicity , drug design , drug distribution , drug screening , drug synthesis , in vivo study , isotope labeling , mouse , nonhuman , structure activity relation , target organ , animal , apoptosis , chemical structure , chemistry , dose response , drug effects , human , synthesis , Animals , Apoptosis , Caco-2 Cells , Dose-Response Relationship, Drug , Drug Design , Humans , Mice , Molecular Structure , Structure-Activity Relationship , Sulfonamides

Abstract:

Several novel thiazolidinone and fused thiazolidinone derivatives bearing benzenesulfonamide moiety were synthesized and confirmed via spectral and elemental analyses. The newly synthesized compounds were evaluated for their cytotoxic activity on colorectal cancer cell line (Caco-2). All the synthesized compounds showed better activity than the reference standards (Doxorubicin and 5-FU). Investigation of the apoptotic activity of the most active compounds revealed that compounds 3a, 5a, 5c and 6c activate both caspase-3 and Fas-ligand in Caco-2�cell line. Compound 3a was the most active compound with caspase-3 concentration of 0.43�nmol/mL and Fas-ligand concentration of 775.2�pg/mL in treated Caco-2�cells. Compound 3a was radiolabeled with 99mTc and its biodistribution pattern was evaluated in�vivo using normal Swiss Albino mice. 99mTc-compound 3a complex didn't exhibit any accumulation in any body organs except for its accumulation in the colon; target organ; where it showed 8.97��1.35 %ID/g at 15min p. i. that elevated till 16.02��2.43 %ID/g at 120min p. i. � 2017 Elsevier Masson SAS