Synthesis and Antitumor Activities of Some New N1-(Flavon-6-yl)amidrazone Derivatives

• Published in: Archiv der Pharmazie (Weinheim) Vol. 347; no. 6; pp. 415 - 422
• Main Authors: Habashneh, Almeqdad Y., El-Abadelah, Mustafa M., Zihlif, Malek A., Imraish, Amer, Taha, Mutasem O.
• Format: Journal Article
• Language: English; German
• Published: WEINHEIM Blackwell Publishing Ltd 01.06.2014; Wiley; Wiley Subscription Services, Inc
• Subjects: 4-Oxo-N-(chromen-6-yl)hydrazonoyl chloride; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antitumor activity; Benzamides - pharmacology; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Drug Design; Flavones - chemical synthesis; Flavones - pharmacology; Fusion Proteins, bcr-abl - antagonists & inhibitors; Fusion Proteins, bcr-abl - chemistry; Fusion Proteins, bcr-abl - metabolism; Humans; Imatinib Mesylate; Inhibitory Concentration 50; K562 Cells; Life Sciences & Biomedicine; MCF-7 Cells; Molecular Docking Simulation; Molecular Structure; N1-(Flavon-6-yl)amidrazones; Oncogenic tyrosine kinases bcr/abl; Pharmacology & Pharmacy; Physical Sciences; Piperazines - pharmacology; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - pharmacology; Pyrimidines - pharmacology; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - chemistry; Receptor, Epidermal Growth Factor - metabolism; Science & Technology; Structure-Activity Relationship; FUNCTIONALIZED FLAVONES; PROTEIN; SERIES; ANALOGS; SCAVENGERS; N1-(Flavon-6-yl)amidrazones; QUERCETIN; INHIBITION; Oncogenic tyrosine kinases bcr/abl; 4-Oxo-N-(chromen-6-yl)hydrazonoyl chloride; BIOLOGICAL EVALUATION; CHALCONES; Antitumor activity; AGENTS
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201300326

A new series of N1‐(flavon‐6‐yl)amidrazones were synthesized by reacting the hydrazonoyl chloride derived from 6‐aminoflavone with the appropriate sec‐cyclic amines. The antitumor activities of these compounds were evaluated on breast cancer (MCF‐7) and leukemic (K562) cell lines. Among the compounds tested, the N‐morpholine derivative was the most active against the MCF‐7 and K562 cell lines, with IC50 values of 5.18 and 2.89 μM, respectively. Our docking studies showed that the N‐morpholino derivative fits and blocks the oncogenic tyrosine kinases bcr/abl and epidermal growth factor receptor (EGFR) in a similar fashion to that of the potent anticancer agent imatinib. A new series of N1‐(flavon‐6‐yl)amidrazones were synthesized by reacting the hydrazonoyl chloride derived from 6‐aminoflavone with the appropriate sec‐cyclic amines. The N‐morpholine derivative was the most active against two cancer cell lines. Docking studies revealed that this derivative fits and blocks the oncogenic tyrosine kinases bcr/abl and EGFR similar to the anticancer agent imatinib.