Correlation of hydrogen-bonding propensity and anticancer profile of tetrazole-tethered combretastatin analogues.

ABSTRACT: A series of 1,5-disubstituted tetrazole-tethered combretastatin analogues with extended hydrogen-bond donors at the ortho-positions of the aryl A and B rings were developed and evaluated for their antitubulin and antiproliferative activity. We wanted to test whether intramolecular hydrogen-bonding used as a conformational locking element in these analogues would improve their activity. The correlation of crystal structures with the antitubulin and antiproliferative profiles of the modified analogues suggested that hydrogen-bond-mediated conformational control of the A ring is deleterious to the bioactivity. In contrast, although there was no clear evidence that intramolecular hydrogen bonding to the B ring enhanced activity, we found that increased substitution on the B ring had a positive

SUBMITTER: Jedhe GS 

PROVIDER: S-EPMC3774141 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature