title: Newly Designed and Synthesized Curcumin Analogs with in vitro Cytotoxicity and Tubulin Polymerization Activity.
abstract: Novel curcumin analogs with 4-piperidone ring were designed, synthesized, and evaluated for their cytotoxic activities against five different cancer cell lines. 3,5-bis(4-Hydroxy-3-methoxybenzylidene)-4-oxo-N-phenylpiperidine-1-carbothioamide (XIIe) exhibited considerable cytotoxic activity with IC50 values in 1-2.5 μm range. In silico and in vitro, studies were also performed to predict the binding affinity of the target compounds to the β-chain of tubulin receptor (PDB code 1SA1) and their abilities to affect microtubules polymerization cycle. 3,5-bis(3-Iodo-5-methoxy-4-propoxybenzylidene)-N-acetylpiperidin-4-one (VIIa) was found to exert 93.3% inhibition of tubulin and destabilization of microtubules in vitro compared to vincristine while, 3,5-bis(3,4,5-trimethoxybenzylidene)-N-benzoylpiperidin-4-one (XIIc) showed high potency in a different way where it exerted 94.8% stabilization of microtubules in vitro compared to positive control paclitaxel.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo, 12311, Egypt.
authors.forename: Iten M
authors.initials: IM
authors.lastname: Fawzy
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo, 12311, Egypt.
authors.forename: Khairia M
authors.initials: KM
authors.lastname: Youssef
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
authors.forename: Nasser S M
authors.initials: NS
authors.lastname: Ismail
authors.affiliation: Division of Clinical Pharmacology, Department of Medical Sciences, Uppsala University Hospital, SE-751 85, Uppsala, Sweden.
authors.forename: Joachim
authors.initials: J
authors.lastname: Gullbo
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
authors.forename: Khaled A M
authors.initials: KA
authors.lastname: Abouzid
mesh_terms: D003474:Curcumin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D003603:Cytotoxins; D014404:Tubulin; D050257:Tubulin Modulators; D003474:Curcumin
keywords: curcumin analogs; cytotoxicity; molecular modeling; tubulin polymerization assay