Synthesis and anticancer potential of certain novel 2-oxo-N'-(2-oxoindolin-3-ylidene)-2H-chromene-3-carbohydrazides

• Published in: European journal of medicinal chemistry 2013-12, Vol.70, p.358-363
• Main Authors: Abdel-Aziz, Hatem A., Elsaman, Tilal, Al-Dhfyan, Abdullah, Attia, Mohamed I., Al-Rashood, Khalid A., Al-Obaid, Abdul-Rahman M.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Chromene-2-ones; Colorectal cancer; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HT29 Cells; Humans; Hydrazides/hydrazones; Hydrazines - chemical synthesis; Hydrazines - chemistry; Hydrazines - pharmacology; Indoline-2,3-dione; K562 Cells; Molecular Structure; Ring-opening; Side population (SP) cells; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.09.060

Treatment of ethyl 3-hydrazinyl-3-oxopropanoate (6) with indoline-2,3-dione derivatives 7a–g gave ethyl 3-oxo-3-(2-(2-oxoindolin-3-ylidene)hydrazinyl)propanoates 8a–g which were allowed to react with the appropriate salicyaldehyde 9a and/or 9b to furnish the chromene-based hydrazones 10a–i. Compounds 10a–i displayed a significant activity against HT-29 colon cancer cell line and a moderate activity against leukemia K562 cell line. Compound 10f emerged as the most active congener toward HT-29 colon cancer cell line with IC50 = 7.98 ± 0.05 μM whereas compound 10c exhibited the best antiproliferative activity against leukemia K562 cell line with IC50 = 9.44 ± 0.02 μM. Moreover, compound 1e showed 87.81 ± 7% inhibition of side population (SP) HT-29 colon cancer stem cells. [Display omitted] The synthesized compounds 10a–i showed a significant activity against HT-29 colon cancer cell line and a moderate activity against leukemia K562 cell line. Compound 10f showed IC50 = 7.98 ± 0.05 μM toward HT-29 whereas 10c exhibited IC50 = 9.44 ± 0.02 μM against K562. •Compounds 10a–i were prepared starting from 6 instead of the claimed hydrazides 2a,b.•In vitro antiproliferative activity of title compounds is determined.•Leukemia K562, breast MDA-MB-468 and colon HT-29 cell lines are used in the study.•Compounds 10c, 10h and 10f are the most active congeners.•1e showed 87.81% inhibition of side population colon HT-29 cancer stem cells.