A new approach for evaluating in vivo anti-leukemic activity using the SCE assay

Man-Made Cytotoxic Steroids: Exemplary Agents for Cancer Therapy

“…Compound 25 , a steroidal ester of p -methyl- m - N , N -bis­(2-chloroethyl)-aminobenzoic acid, showed a spectrum of activities similar to that of steroid 24 in both the cytogenetic and the antileukemic experiments. This finding indicated that the introduction of ketone at the 7-position of the steroidal ligand accounts for its increased activity and is in agreement with several reports stating that the Δ 5 -7-keto steroids are more toxic toward cancerous cells due to their ability to inhibit cell replication …”

“…This finding indicated that the introduction of ketone at the 7-position of the steroidal ligand accounts for its increased activity and is in agreement with several reports stating that the Δ 5 -7-keto steroids are more toxic toward cancerous cells due to their ability to inhibit cell replication. 109 On the basis of the above results and to further explore the effect of the 7-keto group on the antileukemic activity of the nitrogen mustard functionalized steroidal esters, the antileukemic properties of esters of p-N,N-bis(2-chloroethyl)aminophenylacetic acid (PHE, active metabolite of chlorambucil) with 3β-hydroxy-androst-5-ene-7,17-dione, 3β-hydroxy-17βacetamido-androst-5-en-7-one, as well as with their parental nonoxidized steroids 3β-hydroxy-androst-5-en-17-one and 3βhydroxy-17β-acetamido-androst-5-ene were studied. 108 The 7keto derivatives were effective against P-388 and L1210-leukemia bearing mice in comparison to the nonoxidized derivatives.…”

“…Esters of m-[N,Nbis(2-chloroethyl)amino]benzoic acid, p-[N,N-bis(2chloroethyl)amino]-phenylacetic acid, and chlorambucil with B-ring modified cholestane, amidosteroid, and androstane as exemplified by compounds 45−50 (Figure 10) have also been synthesized and were found to have profound antileukemic activity. 59,60,109,144,146 The most potent compound 50 had significantly reduced toxicity level and notable potency against P388 and L1210 leukemia cell lines. 144 The presence of −NHCO− moiety within steroid ring proved to be an important pharmacophore in contrast to the nonmodified steroids as the antineoplastic properties diminished when the B-ring was transformed to a simple 7-ketone.…”

“…Esters of m -[ N , N -bis­(2-chloroethyl)­amino]­benzoic acid, p -[ N , N -bis­(2-chloroethyl)­amino]-phenylacetic acid, and chlorambucil with B-ring modified cholestane, amidosteroid, and androstane as exemplified by compounds 45 – 50 (Figure ) have also been synthesized and were found to have profound antileukemic activity. ,,,, The most potent compound 50 had significantly reduced toxicity level and notable potency against P388 and L1210 leukemia cell lines …”