Elmeligie S.Taher A.T.Khalil N.A.El-said A.H.Pharmaceutical Organic Chemistry DepartmentFaculty of PharmacyCairo UniversityCairoEgypt; Organic Chemistry DepartmentFaculty of PharmacyOctober University for Modern Sciences and Arts (MSA)6th October CityGizaEgypt; Pharmaceutical Organic Chemistry DepartmentFaculty of PharmacyMisr University for Science and Technology6th October CityGizaEgypt2020-01-092020-01-0920172536269https://doi.org/10.1007/s12272-016-0849-yPubMed ID 27747473https://t.ly/1VwlBScopusNovel series of 1,3,4-trisubstituted azetidin-2-one derivatives 8a�p were synthesized and proposed as cytotoxic agents acting via inhibition of tubulin at the colchicine binding site. The design of the target compounds was based upon modification in the structure of the vascular targeting agent combretastatin A-4 (CA-4). The cis double bond linker in CA-4 was replaced with the azetidin-2-one ring aiming to prevent the cis/trans isomerization that suppresses the activity of CA-4, thereby enhancing its antiproliferative activity. All new compounds were investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by four most potent compounds 8g, 8j, 8n and 8o was also evaluated. The synthesis of the final targets was achieved adopting Staudinger reaction. Molecular modeling studies were performed to rationalize the biological results. � 2016, The Pharmaceutical Society of Korea.EnglishOctober University for Modern Sciences and Artsجامعة أكتوبر للعلوم الحديثة والآدابUniversity of Modern Sciences and ArtsMSA UniversityAzetidin-2-oneCombretastatin A4Cytotoxic activityTubulin3 chloro 4 (4 chlorophenyl) 1 (4 methoxyphenyl) 3 methyl azetidin 2 one3 chloro 4 (furan 2 yl) 1 (4 methoxyphenyl)azetidin 2 one4 (2 bromophenyl) 1 (3,4,5 trimethoxyphenyl) 3 (2 thienyl)azetidin 2 one4 (2 bromophenyl) 1 (3,4,5 trimethoxyphenyl) 3 phenylazetidin 2 one4 (2 bromophenyl) 3 chloro 1 (3,4,5 trimethoxyphenyl) 3 methylazetidin 2 one4 (2 bromophenyl) 3 chloro 1 (3,4,5 trimethoxyphenyl)azetidin 2 one4 (2 bromophenyl) 3 chloro 1 (4 methoxyphenyl) 3 methylazetidin 2 one4 (2 bromophenyl) 3 chloro 1 (4 methoxyphenyl)azetidin 2 one4 (3 bromophenyl) 1 (3,4,5 trimethoxyphenyl) 3 (2 thienyl)azetidin 2 one4 (3,4,5 trimethoxyphenyl) 1 (4 methoxyphenyl) 3 (2 thienyl)azetidin 2 one4 (4 bromophenyl) 1 (3,4,5 trimethoxyphenyl) 3 (2 thienyl)azetidin 2 one4 (4 bromophenyl) 1 (3,4,5 trimethoxyphenyl) 3 phenylazetidin 2 one4 (4 bromophenyl) 3 chloro 1 (4 methoxyphenyl)azetidin 2 one4 (4 chlorophenyl) 1 (3,4,5 trimethoxyphenyl) 3 (2 thienyl)azetidin 2 one4 (4 chlorophenyl) 1 (3,4,5 trimethoxyphenyl) 3 phenylazetidin 2 one4 (4 chlorophenyl) 1 (4 methoxyphenyl) 3 (2 theinyl)azetidin 2 oneazetidin 2 one derivativeazetidine derivativecolchicinecombretastatin A4cytotoxic agentunclassified drugazetidineazetidine derivativebibenzyl derivativecombretastatincytotoxinantiproliferative activityArticlecytotoxicitydrug binding sitedrug designdrug structuredrug synthesisHCT 116 cell linehumanhuman cellin vitro studyisomerizationMCF-7 cell linemicrotubule assemblymolecular modelStaudinger reactionstructure activity relationcell survivaldrug effectsphysiologysynthesisAzetidinesBibenzylsCell SurvivalCytotoxinsHCT116 CellsHumansMCF-7 CellsArticlehttps://doi.org/10.1007/s12272-016-0849-yPubMed ID 27747473