Stereochemistry as a determinant of the anti-leukemic potency of halopyridyl and thiazolyl thiourea compounds

Taracad K. Venkatachalam; Alexi O. Vassilev; Alexi Benyunov; Olga O. Grigoriants; Heather E. Tibbles; Fatih M. Uckun

doi:10.2174/157018007780867870

Stereochemistry as a determinant of the anti-leukemic potency of halopyridyl and thiazolyl thiourea compounds

Taracad K. Venkatachalam, Alexi O. Vassilev, Alexi Benyunov, Olga O. Grigoriants, Heather E. Tibbles, Fatih M. Uckun

Medicine - Pulmonary, Allergy, Critical

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Pages (from-to)	318-326
Number of pages	9
Journal	Letters in Drug Design and Discovery
Volume	4
Issue number	5
DOIs	https://doi.org/10.2174/157018007780867870
State	Published - Jul 2007

Keywords

Caspase
Leukemia
Stereochemistry
Thiourea
Zebrafish

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title = "Stereochemistry as a determinant of the anti-leukemic potency of halopyridyl and thiazolyl thiourea compounds",

abstract = "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.",

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T1 - Stereochemistry as a determinant of the anti-leukemic potency of halopyridyl and thiazolyl thiourea compounds

AU - Venkatachalam, Taracad K.

AU - Vassilev, Alexi O.

AU - Benyunov, Alexi

AU - Grigoriants, Olga O.

AU - Tibbles, Heather E.

AU - Uckun, Fatih M.

PY - 2007/7

Y1 - 2007/7

N2 - 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.

AB - 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.

KW - Caspase

KW - Leukemia

KW - Stereochemistry

KW - Thiourea

KW - Zebrafish

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ER -

Stereochemistry as a determinant of the anti-leukemic potency of halopyridyl and thiazolyl thiourea compounds

Abstract

Keywords

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