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Newly Designed and Synthesized Curcumin Analogs with in vitro Cytotoxicity and Tubulin Polymerization Activity
Author(s) -
Fawzy Iten M.,
Youssef Khairia M.,
Ismail Nasser S. M.,
Gullbo Joachim,
Abouzid Khaled A. M.
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12464
Subject(s) - tubulin , in vitro , curcumin , chemistry , cytotoxicity , microtubule , paclitaxel , microtubule polymerization , protein data bank (rcsb pdb) , stereochemistry , cytotoxic t cell , biochemistry , biology , cancer , microbiology and biotechnology , genetics
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 ( XII e) exhibited considerable cytotoxic activity with IC 50 values in 1–2.5 μ m 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 1 SA 1) and their abilities to affect microtubules polymerization cycle. 3,5‐bis(3‐Iodo‐5‐methoxy‐4‐propoxybenzylidene)‐ N ‐acetylpiperidin‐4‐one ( VII a) 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 ( XII c) showed high potency in a different way where it exerted 94.8% stabilization of microtubules in vitro compared to positive control paclitaxel.