Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents

Abstract

A group of novel trimethoxyphenyl (TMP)-based analogues were synthesized by varying the azalactone ring of 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxybenzylidene)oxazolone 1 and characterized using NMR spectral data as well as elemental microanalyses. All synthesized compounds were screened for their cytotoxic activity utilizing the hepatocellular carcinoma (HepG2) cell line. Compounds 9, 10 and 11 exhibited good cytotoxic potency with IC50 values ranging from 1.38 to 3.21 μM compared to podophyllotoxin (podo) as a reference compound. In addition, compounds 9, 10 and 11 exhibited potent inhibition of β-tubulin polymerization. DNA flow cytometry analysis of compound 9 shows cell cycle disturbance at the G2/M phase and a significant increase in Annexin-V-positive cells compared with the untreated control. Compound 9 was further studied regarding its apoptotic potential in HepG2 cells; it decreased the level of MMP and Bcl-2 as well as boosted the level of p53 and Bax compared with the control HepG2 cells.

Synthesis, Characterization and Biological Evaluation of New Enamide Fluorinated‐Schiff Base Derivatives as Potential Cytotoxic and Apoptosis‐Inducing Agents

“…In order to determine whether the furfural Schiff base derivative 5 induced reduction in cell viability was responsible for the induction of apoptotic cellular death. MCF‐7 cells were labelled with PI and fluorochrome Annexin‐V, and the number of apoptotic cells was counted using the FACS method according previously reported procedure [35] . During apoptosis, phosphatidylserine is translocated from the inner aspect of the outer leaflet of the plasma membrane, which may be detected by measuring the Annexin V to phosphatidylserine ratio [36] .…”

“…MCF-7 cells were labelled with PI and fluorochrome Annexin-V, and the number of apoptotic cells was counted using the FACS method according previously reported procedure. [35] During apoptosis, phosphatidylserine is translocated from the inner aspect of the outer leaflet of the plasma membrane, which may be detected by measuring the Annexin V to phosphatidylserine ratio. [36] On the contrary, the impermeable dye PI preferentially enters necrotic and late apoptotic cells.…”

New Heterocyclic Compounds from Oxazol-5(4H)-one and 1,2,4-Triazin-6(5H)-one Classes: Synthesis, Characterization and Toxicity Evaluation

“…These compounds, also known as azlactones, are classified as saturated or unsaturated, according to the type of exocyclic bond linked to the carbon from four position of this core [ 7 ]. Unsaturated oxazolones are important synthons for the synthesis of different compounds with vast biological potential, including amino acids, peptides, amides [ 8 , 9 , 10 , 11 , 12 ] and five- or six-membered heterocycles (imidazolones, tiazolones, triazinones, etc.) [ 7 , 8 , 9 , 12 ].…”

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues

“…Numerous compounds that resemble CA-4 have been created and studied as possible anticancer drugs. − Two aromatic rings are connected by a different moiety, such as olefins, enamides, or heterocyclic functions, to form CA-4 analogues. − According to SAR studies, ring A’s trimethoxy group is a crucial pharmacophoric site for tubulin, whereas ring B’s halogenated phenyl group preserves the antitubulin activity. , The maintenance of tissue growth and homeostasis depends heavily on apoptosis, a critical cellular function. , Apoptotic pathway regulation issues have been connected to a variety of diseases, including cancer . In order to find effective cancer treatments, it has become common practice to design and prepare novel chemotherapeutic chemicals that are capable of triggering apoptotic death. − …”

“… 23 In order to find effective cancer treatments, it has become common practice to design and prepare novel chemotherapeutic chemicals that are capable of triggering apoptotic death. 24 − 26 …”