Details

Autor(en) / Beteiligte

• Ilovaisky, Alexey I.
• Scherbakov, Alexander M.
• Merkulova, Valentina M.
• Chernoburova, Elena I.
• Shchetinina, Marina A.
• Andreeva, Olga E.
• Salnikova, Diana I.
• Zavarzin, Igor V.
• Terent’ev, Alexander O.

Titel

Secosteroid–quinoline hybrids as new anticancer agents

Ist Teil von

• The Journal of steroid biochemistry and molecular biology, 2023-04, Vol.228, p.106245-106245, Article 106245

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• An elegant approach to unknown secosteroid–quinoline hybrids is disclosed. A series of 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N′-(iso)quinolylmethylene]hydrazides was prepared and these novel type of secosteroids was screened for antiproliferative activity against estrogen-responsive human breast cancer cell line MCF-7. Most of the synthesized compounds showed a cytotoxic effect superior to that of reference drug cisplatin; the lead compound exhibits the highest activity with the IC50 value of about 0.8 μM and is 7 times more active than cisplatin. A high selectivity index was observed for the hit 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N′-quinolylmethylene]hydrazides 2a and 2c. Compounds 2a and 2c evaluated in luciferase reporter assays exhibited high antiestrogenic potency which was superior to that of tamoxifen. These hit compounds were characterized by high activity against MCF-7 cells that retained towards multidrug-resistant NCI/ADR-RES cells. [Display omitted] •A broad series of secosteroid–quinoline hybrids highly active towards MCF-7 breast cancer cells were synthesized.•A number of obtained compounds were 2–7 times more active than the reference drug cisplatin.•Hit compounds 2a and 2c showed high cytotoxicity for MCF-7 cells and multidrug-resistant NCI/ADR-RES cancer cells.•Compounds 2a and 2c tested in luciferase reporter assays exhibited high antiestrogenic potency.