Novel diamidino-substituted derivatives of phenyl benzothiazolyl and dibenzothiazolyl furans and thiophenes: synthesis, antiproliferative and DNA binding properties.
A series of new diamidino-, diisopropylamidino-, and diimidazolinyl-substituted derivatives of phenyl benzothiazolyl and dibenzothiazolyl furans and thiophenes were successfully prepared and evaluated for their antiproliferative activity on tumor cell lines in vitro, DNA binding propensity, and sequence selectivity as well as cellular distribution. A strong antiproliferative effect of the tested compounds was observed on all tested cell lines in a concentration-dependent response pattern. In general, imidazolinyl-substituted derivatives and/or the thiophene core were in correlation with increased antiproliferative activity. Two compounds (2b and 3b) were chosen for biological studies due to their differential antiproliferative properties. The DNA binding properties of this new series of compounds were assessed and evidenced their efficient minor groove binding properties with preferential interaction at AT-rich sites. Both compounds also present nuclear subcellular localization, suggesting that their cellular mode of action implies localization in the DNA compartment and direct inhibition of DNA replication and induction of apoptosis.
Racané
Livio
L
Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Baruna Filipovića 28a 10000 Zagreb, Croatia.
Tralić-Kulenović
Vesna
V
Kraljević Pavelić
Sandra
S
Ratkaj
Ivana
I
Peixoto
Paul
P
Nhili
Raja
R
Depauw
Sabine
S
Hildebrand
Marie-Paule
MP
David-Cordonnier
Marie-Hélène
MH
Pavelić
Kresimir
K
Karminski-Zamola
Grace
G
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002942:Circular Dichroism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D018983:DNA Footprinting / Q000379:methods; D005663:Furans / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D015394:Molecular Structure; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*
D005663:Furans; D013876:Thiophenes; D004247:DNA