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Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents.

ABSTRACT: A small and focused library of steroidal non-fused and fused pyrimidines was prepared from pregnenolone acetate and diosgenin, respectively. The key step was the cycloaddition reaction of nitrogen-containing 1,3-binucleophiles with the steroidal α,β-unsaturated ketone. Urea, thiourea and guanidine reacted in a similar manner and afforded the steroidal pyrimidines in good yields. The antiproliferative tests against human tumor cell lines gave GI50 values in the micromolar range and had no effect on healthy fibroblasts. Additional experiments indicated that the compounds did not act as P-glycoprotein substrates, thus avoiding the rise of drug resistance. The fused steroidal pyrimidinethione was selected as drug lead for further testing due to its strong antiproliferative activities within the low micromolar range.

SUBMITTER: Cortes-Percino A

PROVIDER: S-EPMC6832952 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents.

Cortés-Percino Alejandra A Vega-Báez José Luis JL Romero-López Anabel A Puerta Adrián A Merino-Montiel Penélope P Meza-Reyes Socorro S Padrón José M JM Padrón José M JM Montiel-Smith Sara S

Molecules (Basel, Switzerland) 20191012 20

A small and focused library of steroidal non-fused and fused pyrimidines was prepared from pregnenolone acetate and diosgenin, respectively. The key step was the cycloaddition reaction of nitrogen-containing 1,3-binucleophiles with the steroidal α,β-unsaturated ketone. Urea, thiourea and guanidine reacted in a similar manner and afforded the steroidal pyrimidines in good yields. The antiproliferative tests against human tumor cell lines gave GI<sub>50</sub> values in the micromolar range and had ...[more]

PMID: 31614780

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