Tags

Type your tag names separated by a space and hit enter

Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents.
Molecules 2019; 24(20)M

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.

Authors+Show Affiliations

Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, Pue., Mexico. ale891930@hotmail.com.Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, Pue., Mexico. jose.vega@correo.buap.mx.Instituto de Física "Luis Rivera Terrazas" Benemérita Universidad Autónoma de Puebla Ecocampus Valsequillo, 72960 San Pedro Zacachimalpa, Pue., Mexico. anabelrl@ifuap.buap.mx.BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, c/ Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain. apuertaarocha@gmail.com.Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, Pue., Mexico. penelope.merino@correo.buap.mx.Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, Pue., Mexico. maria.meza@correo.buap.mx.BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, c/ Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain. jmpadron@ull.es.Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, Pue., Mexico. maria.montiel@correo.buap.mx.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31614780

Citation

Cortés-Percino, Alejandra, et al. "Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents." Molecules (Basel, Switzerland), vol. 24, no. 20, 2019.
Cortés-Percino A, Vega-Báez JL, Romero-López A, et al. Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents. Molecules. 2019;24(20).
Cortés-Percino, A., Vega-Báez, J. L., Romero-López, A., Puerta, A., Merino-Montiel, P., Meza-Reyes, S., ... Montiel-Smith, S. (2019). Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents. Molecules (Basel, Switzerland), 24(20), doi:10.3390/molecules24203676.
Cortés-Percino A, et al. Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents. Molecules. 2019 Oct 12;24(20) PubMed PMID: 31614780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents. AU - Cortés-Percino,Alejandra, AU - Vega-Báez,José Luis, AU - Romero-López,Anabel, AU - Puerta,Adrián, AU - Merino-Montiel,Penélope, AU - Meza-Reyes,Socorro, AU - Padrón,José M, AU - Montiel-Smith,Sara, Y1 - 2019/10/12/ PY - 2019/09/04/received PY - 2019/09/30/revised PY - 2019/10/11/accepted PY - 2019/10/17/entrez KW - antiproliferative activity KW - cycloaddition reactions KW - heterocycle KW - pyrimidine KW - steroids JF - Molecules (Basel, Switzerland) JO - Molecules VL - 24 IS - 20 N2 - 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. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/31614780/Synthesis_and_Evaluation_of_Pyrimidine_Steroids_as_Antiproliferative_Agents L2 - http://www.mdpi.com/resolver?pii=molecules24203676 DB - PRIME DP - Unbound Medicine ER -