Medicinal Chemistry‐driven Approach to Novel 2‐Substituted Benzoxazole – Estradiol Chimeras Synthesis, Anticancer Activity and Early ADME Profile /

The efficient synthesis of novel estradiol‐based A‐ring‐fused oxazole derivatives, which can be considered as benzoxazole‐steroid domain‐integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2‐aminophenol precursors by hetero...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Kovács Ferenc
Huliák Ildikó
Árva Hédi
Csontné Kiricsi Mónika
Erdős Dóra
Kocsis Marianna
Takács Gergely
Balogh György Tibor
Nagyné Frank Éva
Dokumentumtípus: Cikk
Megjelent: 2023
Sorozat:CHEMMEDCHEM 18 No. 22
Tárgyszavak:
doi:10.1002/cmdc.202300352

mtmt:34147665
Online Access:http://publicatio.bibl.u-szeged.hu/29276
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520 3 |a The efficient synthesis of novel estradiol‐based A‐ring‐fused oxazole derivatives, which can be considered as benzoxazole‐steroid domain‐integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2‐aminophenol precursors by heterocycle formation or functional group interconversion (FGI) strategies. According to 2D projection‐based t‐distributed stochastic neighbor embedding (t‐SNE), the novel molecules were proved to represent a new chemical space among steroid drugs. They were characterized based on critical physicochemical parameters using in silico and experimental data. The performance of the compounds to inhibit cell proliferation was tested on four human cancer cell lines and non‐cancerous cells. Further examinations were performed to reveal IC50 and lipophilic ligand efficiency (LLE) values, cancer cell selectivity, and apoptosis‐triggering features. Pharmacological tests and LLE metric revealed that some derivatives, especially the 2‐(4‐ethylpiperazin‐1‐yl)oxazole derivative exhibit strong anticancer activity and trigger the apoptosis of cancer cells with relatively low promiscuity risk similarly to the structurally most closely‐related and intensively studied anticancer agent, 2‐methoxy‐estradiol. 
650 4 |a Kémiai tudományok 
700 0 1 |a Huliák Ildikó  |e aut 
700 0 1 |a Árva Hédi  |e aut 
700 0 2 |a Csontné Kiricsi Mónika  |e aut 
700 0 2 |a Erdős Dóra  |e aut 
700 0 2 |a Kocsis Marianna  |e aut 
700 0 2 |a Takács Gergely  |e aut 
700 0 2 |a Balogh György Tibor  |e aut 
700 0 2 |a Nagyné Frank Éva  |e aut 
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856 4 0 |u http://publicatio.bibl.u-szeged.hu/29276/3/34147665_megjelent.pdf  |z Dokumentum-elérés