Document Detail

New structural analogues of Tubulozole induce apoptosis, [Ca2+]i modifications and cytoskeletal disorganization in glial (GL15) and neuronal-like (PC12) cell lines.
MedLine Citation:
PMID:  11129979     Owner:  NLM     Status:  MEDLINE    
The synthesis and the biological activity of (+/-)-cis- and (+/-)-trans-[4-[[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1, 3-dioxolan-4-yl]methylthio]phenyl]carbamic acid ethyl esters (2a and 2b) are discussed. They were designed as structural analogues of Tubulozole, a synthetic tubulin polymerisation inhibitor with antimitotic properties. Biological tests were carried out on PC12, a neuronal-like cell line derived from rat pheochromocytoma, and on GL15, a cell line derived from human glioblastoma. The exposure (from 5 to 20 h) of GL15 and PC12 cells to different concentrations (0.1-1000 microM; IC50 approximately 1 microM) of 2a or 2b resulted in a drastic decrease in the number of viable cells without an apparent effect on the cell distribution in the various phases of the cell cycle. Compound 2a or 2b (10 microM) induced cell death by activating apoptosis. This was correlated with the activation of an oscillating Ca(2+)-dependent mechanism which increased the intracellular calcium concentration ([Ca2+]i) via Ca(2+)-release from internal stores. Moreover, 2a (10 microM) also induced severe damage of cytoskeletal F-actin filaments after a 5 h incubation in GL15 cells. This was also observed but to a smaller extent, for 2b. Under the same experimental conditions, PC12 cells showed similar actin deregulation.
S Castellano; M A Mariggiò; S Guarnieri; G Stefancich; T Pietrangelo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archiv der Pharmazie     Volume:  333     ISSN:  0365-6233     ISO Abbreviation:  Arch. Pharm. (Weinheim)     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-20     Completed Date:  2001-01-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0330167     Medline TA:  Arch Pharm (Weinheim)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  373-80     Citation Subset:  IM    
Dipartimento di Scienze Farmaceutiche, Università di Trieste, Piazzale Europa 1, 34127 Trieste, Italy.
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MeSH Terms
Adrenal Gland Neoplasms
Apoptosis / drug effects*
Cytoskeleton / drug effects*,  ultrastructure
Dioxolanes / chemical synthesis*,  chemistry,  pharmacology*
Molecular Structure
Neuroglia / cytology,  drug effects*,  ultrastructure
Neurons / cytology,  drug effects*,  ultrastructure
PC12 Cells
Structure-Activity Relationship
Reg. No./Substance:
0/Dioxolanes; 84697-22-3/tubulazole

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