Stereochemistry as a Determinant of the Anti-Leukemic Potency of Halopyridyl and Thiazolyl Thiourea Compounds
Taracad K. Venkatachalam,
Alexi O. Vassilev,
Olga O. Grigoriants,
Heather E. Tibbles,
Fatih M. Uckun.
Chiral derivatives of two cyclohexylethyl halopyridyl thiourea compounds (HI-509 and HI-510), two α -methyl benzyl halopyridyl compounds (HI-511 and HI-512), and a cyclohexyl ethyl thiazolyl thiourea compound (HI-513) were synthesized and evaluated for their anti-cancer activity. Preliminary screening indicated that the (S)- isomers displayed improved activity in comparison with (R)- enantiomers to inhibit tubulin polymerization and activate caspase- 3. In accordance with these results, the thiourea derivatives displayed potent anti-cancer activity against human B-lineage (Nalm-6) and T-lineage (Molt-3) acute lymphoblastic leukemia cell lines. Based on the results we conclude that the anti-leukemic activity of these compounds also depends on their chirality.
Keywords: Stereochemistry, Thiourea, Zebrafish, Caspase, Leukemia
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