120793-61-5Relevant articles and documents
Synthesis, pharmacological evaluation and Molecular modelling studies of pregnenolone derivatives as inhibitors of human dihydrofolate reductase
Bilal Tufail, Muhammad,Aamir Javed, Muhammad,Ikram, Muhammad,Mahnashi, Mater H.,Alyami, Bandar A.,Alqahtani, Yahya S.,Sadiq, Abdul,Rashid, Umer
, (2021)
In current study, we synthesized chalcone derivatives (13a–c) via base-catalyzed Claisen-Schmidt condensation reaction. We further treated diamino compounds with synthesized chalcones to produce 3,4-dihydropyrimidin-2(1H)-one (18a–c), 3,4-dihydropyrimidin-2(1H)-thione (19a–c) and 2-aminopyrimidine (20a–c) derivatives of pregnenolone by cyclization reaction. Cell viability test of synthesized steroidal chalcones and their pyrimidine and thiopyrimidine derivatives against human breast (MCF-7), human lung (A549) and human prostate (PC-3) cancer cell lines was performed using (4,5‐dimethylthiazol‐2‐yl)-2,5‐diphenyltetrazolium bromide (MTT), assay. Compounds were further evaluated for their inhibition potential against recombinant human DHFR (rhDHFR). All compounds showed activity from low micromolar to submicromolar range. Compound 20b with IC50 value of 180 nM emerged as most potent compound against rhDHFR. Interaction of the newly synthesized pregnenolone derivatives with hDHFR and estrogen receptor alpha (ERα) were also explored via docking simulations. The overall results of hDHFR inhibition have shown that these analogues can be further optimized and developed as potent anticancer agents.
Synthesis and evaluation of pyrimidine steroids as antiproliferative agents
Cortés-Percino, Alejandra,Vega-Báez, José Luis,Romero-López, Anabel,Puerta, Adrián,Merino-Montiel, Penélope,Meza-Reyes, Socorro,Padrón, José M.,Montiel-Smith, Sara
, (2019/10/28)
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.
Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents
Shi, Yun-Kai,Wang, Bo,Shi, Xiao-Li,Zhao, Yuan-Di,Yu, Bin,Liu, Hong-Min
, p. 11 - 22 (2018/01/10)
A series of new steroidal pyridines have been synthesized through the based-promoted three-component reaction and preliminarily evaluated for their antiproliferative activity against different types of cancer cell lines. SARs studies showed that the heterocyclic rings attached to the 4-position of the pyridine ring were preferred over the phenyl rings for the activity. Among these compounds, the most potent compound exhibited good growth inhibition against all the tested cancer cells, especially for PC-3 cells with an IC50 value of 1.55 μM. Further mechanistic studies revealed that the most potent compound inhibited colony formation, migration and evasion of PC-3 cells in a concentration-dependent manner as well as induced apoptosis of PC-3 cells possibly through the mitochondria-related apoptotic pathways. Caspase-3/-9 and PARP were activated, finally leading to the apoptosis of PC-3 cells. For the androgen-sensitive (AR+) prostate cancer cell line LNCaP, the most potent compound was less potent than abiraterone with the IC50 value of 8.48 and 3.29 μM, respectively. The most potent compound could be used as a starting point for the development of new steroidal heterocycles with improved anticancer potency and selectivity. The synthesized steroidal pyridines contain the functional -OEt and CN groups, which could be used for further modifications for the construction of the steroid library.
