Synthesis and antitumor evaluation of novel diarylsulfonylurea derivatives: molecular modeling applications.
Eur J Med Chem
; 45(2): 689-97, 2010 Feb.
Article
in En
| MEDLINE
| ID: mdl-19939520
ABSTRACT
Some new ethyl 2-[3-(4-unsubstituted or 4-substituted phenylsufonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylates 3a-c, 2-[3-(phenylsulfonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbohydrazides 4a-f, 3-phenylsulfonyl-6,7,8,9-tetrahydro-5H-cyclohepta[1',2'4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)dione 5 and 3-(phenylsulfonyl)-1-[3-(alkylaminocarbonyl or substituted piperazinylcarbonyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-2-yl]ureas 6a-d have been synthesized and tested for their antitumor activity. Among these compounds, 4a, 4c and 4d exhibited a broad spectrum antitumor activity with full panel (MG-MID) median growth inhibition (GI(50)) of 3.5, 4.9 and 4.0muM respectively. In addition, compounds 4c, 4d, 6c and 6d proved to be of moderate selectivity toward colon cancer cell lines with ratios of 3.1, 1.2, 3.6 and 3.0 respectively. Molecular modeling and pharmacophore prediction methods are used to study the antitumor activity of the most active compounds compared with the least active species by means of the molecular mechanic method.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urea
/
Models, Molecular
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2010
Document type:
Article
Affiliation country:
Egypt