Synthesis, antitumor activity, and mechanism of action of 6-acrylic phenethyl ester-2-pyranone derivatives

Abstract

Based on the scaffolds of caffeic acid phenethyl ester (CAPE) as well as bioactive lactone-containing compounds, 6-acrylic phenethyl ester-2-pyranone derivatives were synthesized and evaluated against five tumor cell lines (HeLa, C6, MCF-7, A549, and HSC-2). Most of the new derivatives exhibited moderate to potent cytotoxic activity. Moreover, HeLa cell lines showed higher sensitivity to these compounds. Particularly, compound 5o showed potent cytotoxic activity (IC50 = 0.50 – 3.45 μM) against the five cell lines. Further investigation on the mechanism of action showed that 5o induced apoptosis, arrested the cell cycle at G2/M phases in HeLa cells, and inhibited migration through disruption of the actin cytoskeleton. In addition, ADME properties were also calculated in silico, and compound 5o showed good ADMET properties with good absorption, low hepatotoxicity, and good solubility, and thus, could easily be bound to carrier proteins, without inhibition of CYP2D6. A structure-activity relationship (SAR) analysis indicated that compounds with ortho-substitution on the benzene ring exhibited obviously increased cytotoxic potency. This study indicated that compound 5o is a promising compound as an antitumor agent.

Large-Scale Bioinformatics Analysis of Bacillus Genomes Uncovers Conserved Roles of Natural Products in Bacterial Physiology

“…Alkylpyrones OH and methoxy (OMe) were synthesized according to procedures in references 64 to 66 . All reactions were carried out in an oven-dried, round-bottom flask with stirring as noted in Fig.…”

Triarylborane‐Catalyzed Alkenylation Reactions of Aryl Esters with Diazo Compounds

“…These compounds are common starting materials for the synthesis of heterocycles such as pyran‐2‐ones through a simple metal‐ or borane‐catalyzed cyclization reaction . Such pyran‐2‐ones are omnipresent in many bioactive natural products which display inter alia antimicrobial, anti‐HIV, and antitumor activity …”

“…[10,11] Such pyran-2-ones are omnipresent in many bioactive natural products which display inter alia antimicrobial, anti-HIV, and antitumor activity. [12] Initially, we reacted dimethyl 2-diazomalonate (1 a) with 1-(4-fluorophenyl)-3-(trimethylsilyl)prop-2-yn-1-yl-4-fluorobenzoate (2 a) in a 1:1.1 ratio in trifluorotoluene (TFT) solvent (Table 1). In the absence of a borane catalyst no reaction occurred after 22 h at 65 8C (Table 1, entry 1).…”

Triarylboran‐katalysierte Alkenylierungen von Arylestern mit Diazoverbindungen

“…[10,11] Solche Pyran-2-one sind in vielen bioaktiven Naturstoffen allgegenwärtig, die unter anderem antimikrobielle, Anti-HIV-und Antitumoraktivität aufweisen. [12] Zunächst reagierten wir Dimethyl- 1,.…”

“…TFT erwies sich als das beste Lçsungsmittel für die Reaktion, während Toluol, Dichlormethan und Hexan eine niedrigere Ausbeute des Produkts zeigten und THF dazu führte, dass kein gewünschtes Produkt gebildet wurde (Tabelle 1, Nr. [12][13][14][15]. Schließlich untersuchten wir die Wirkung verschiedener Abgangsgruppen R 1 auf den Ester (Tabelle 1), einschließlich 4-FC 6 H 4 , CF 3 , Me, Ph und t Bu.…”