Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors

  • J Med Chem. 2006 Oct 19;49(21):6425-8. doi: 10.1021/jm060804a.
Romeo Romagnoli  1 ,  Pier Giovanni Baraldi ,  Vincent Remusat ,  Maria Dora Carrion ,  Carlota Lopez Cara ,  Delia Preti ,  Francesca Fruttarolo ,  Maria Giovanna Pavani ,  Mojgan Aghazadeh Tabrizi ,  Manlio Tolomeo ,  Stefania Grimaudo ,  Jan Balzarini ,  Mary Ann Jordan ,  Ernest Hamel
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy. [email protected]
PMID: 17034150 DOI: 10.1021/jm060804a
Abstract

2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para-position of the 5-phenyl group showed antiproliferative activity in the order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of Apoptosis.