Mohamed K.O.Nissan Y.M.El-Malah A.A.Ahmed W.A.Ibrahim D.M.Sakr T.M.Motaleb M.A.Pharmaceutical Organic Chemistry DepartmentFaculty of PharmacyCairo UniversityEgypt; Pharmaceutical Chemistry DepartmentFaculty of PharmacyCairo UniversityKasr Elini St.Cairo11562Egypt; Pharmaceutical Chemistry DepartmentFaculty of PharmacyOctober University for Modern Sciences and Arts (MSA)GizaEgypt; National Cancer InstituteCancer Biology DepartmentCairo UniversityEgypt; Faculty of ScienceCairo UniversityCairoEgypt; Radioactive Isotopes and Generator DepartmentHot Labs CenterAtomic Energy AuthorityP.O. Box 13759CairoEgypt; Labeled Compounds DepartmentHot Labs CenterAtomic Energy AuthorityP.O. Box 13759CairoEgypt2020-01-092020-01-0920172235234https://doi.org/10.1016/j.ejmech.2017.04.069PubMed ID 28463785https://t.ly/GgZxbScopusMSA Google ScholarSeveral 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 SASEnglishOctober University for Modern Sciences and Artsجامعة أكتوبر للعلوم الحديثة والآدابUniversity of Modern Sciences and ArtsMSA UniversityApoptosisCaspase-3Fas-ligandRadiolabelingTechnetium-99�mThiazolidinone4 [(3 phenylthiazolo[4,5 c]isoxazol 5 yl)amino]benzenesulfonamide4 [(5 benzylidene 4 oxo 4,5 dihydrothiazol 2 yl)amino]benzenesulfonamide4 [(5 oxo 7 phenyl 5,6 dihydrothiazolo[4,5 d]pyrimidin 2yl)amino]benzenesulfonam4 [(7 phenyl 5 thioxo 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl)amino]benzenesulfonamide4 [[3 (4 chlorophenyl)thiazolo[4,5 c]isoxazol 5 yl]amino]benzenesulfonamide4 [[3 (4 methoxyphenyl)thiazolo[4,5 c]isoxazol 5 yl]amino]benzenesulfonamide4 [[5 oxo 7 (4 chlorophenyl) 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl]amino]benzenesulfonamide4 [[5 oxo 7 (4 methoxyphenyl) 5,6 dihydrothiazolo[4,5-d]pyrimidin 2 yl]amino]benzenesulfonamide4 [[7 (4 chlorophenyl) 5 thioxo 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl]amino]benzenesulfonamide4 [[7 (4 methoxyphenyl) 5 thioxo 5,6 dihydrothiazolo[4,5 d]pyrimidin 2 yl]amino]benzenesulfonamideapoptosis inhibitorcaspase 3cytotoxic agentdoxorubicinFas ligandfluorouracilsulfonamidetechnetium 99munclassified drugsulfonamidealbino mouseanimal experimentArticleCaco-2 cell linecontrolled studycytotoxicitydrug designdrug distributiondrug screeningdrug synthesisin vivo studyisotope labelingmousenonhumanstructure activity relationtarget organanimalapoptosischemical structurechemistrydose responsedrug effectshumansynthesisAnimalsApoptosisCaco-2 CellsDose-Response Relationship, DrugDrug DesignHumansMiceMolecular StructureStructure-Activity RelationshipSulfonamidesArticlehttps://doi.org/10.1016/j.ejmech.2017.04.069PubMed ID 28463785