Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization.
AIM
Discovery of novel series of colchicine binding site inhibitors (CBSIs).


MATERIALS & METHODS
Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.7c, 7e and 11a were more potent than colchicine with IC50 of 0.09, 0.05 and 0.06 μM, and percentage inhibition in tubulin polymerization of 95.2, 96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at G2/M phase and induced apoptosis and were able to bind the colchicine binding site of tubulin with comparable affinity to colchicine. Docking study showed that these compounds may interact with tubulin exploiting a binding cavity not commonly reported in the binding of CBSI.


CONCLUSION
Compounds 7c and 11a may be considered as promising CBSI based on their excellent activity and favorable drug likeness profile.
['Moussa|Shaimaa A|SA|', 'A Osman|Essam Eldin|EE|', 'Eid|Nahed M|NM|', 'Abou-Seri|Sahar M|SM|', 'El Moghazy|Samir M|SM|']
D000970:Antineoplastic Agents D001665:Binding Sites D002453:Cell Cycle D045744:Cell Line, Tumor D003078:Colchicine D015195:Drug Design D004354:Drug Screening Assays, Antitumor D005663:Furans D054879:Halogenation D006801:Humans D007938:Leukemia D062105:Molecular Docking Simulation D009369:Neoplasms D058105:Polymerization D014404:Tubulin D050257:Tubulin Modulators
5-(4-chlorophenyl)furan tubulin colchicine