Secosteroid–quinoline hybrids as new anticancer agents. Issue 228 (April 2023)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 228(2022)
• Publication Date: 2023-04
• Subjects: Secosteroids -- Quinolines -- Hydrazides -- Azomethines -- Breast cancer -- Cytotoxicity -- Estrogen receptor α; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2022.106245
• Languages: English
• ISSNs: 0960-0760

Abstract

Abstract: 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. Graphical Abstract: ga1 Highlights: 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.