Synthesis of DAAS derivatives and their enhancement of HL-60 leukemia cell differentiation

Abstract

DAAS is the diacetoxy acetal derivative of a-santonin and induces HL-60 cell differentiation into granulocytes. In this report, we investigated the structure-activity relationship (SAR) of DAAS derivatives in the differentiation of human HL-60 leukemia cells. Although its derivatives themselves had less effect on HL-60 cell differentiation than DAAS, the monoacetyl derivative, 2, mainly induced HL-60 cell differentiation. Moreover, compound 2 synergistically enhanced all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation when combined with 50 nM ATRA, a well-known differentiation inducer. This enhancing effect is similar to that of DAAS in ATRA-induced differentiation.

Synthesis of C 6-epimer derivatives of diacetoxy acetal derivative of santonin and their inducing effects on HL-60 leukemia cell differentiation

“…We earlier reported that activity order was DAAS (Diacetyl ) > C 13 -monoacetyl >> C 6 -monoacetly ≈ Diol (1) in DAAS derivatives (Kim et al, 2008a). But in its C 6 -epimer series, activity order showed some different fashion from DAAS.…”

“…1), the acetal analogue of α-santonin that contains a non-lactone ring, had remarkable anti-leukemic activities, inducing HL-60 cell differentiation via down-regulation of NF-κB binding activity (Kim et al, 2006a). Also, we have investigated the SAR of DAAS derivatives (Kim et al, 2006b;Kim et al, 2008a).…”