Synthesis of Flavonols and Assessment of Their Biological Activity as Anticancer Agents.

A series of flavanols were synthesized to assess their biological activity against human non-small cell lung cancer cells (A549). Among the sixteen synthesized compounds, it was observed that compounds 6k (3.14 ± 0.29 µM) and 6l (0.46 ± 0.02 µM) exhibited higher potency compared to 5-fluorouracil (5-Fu, 4.98 ± 0.41 µM), a clinical anticancer drug which was used as a positive control. Moreover, compound 6l (4'-bromoflavonol) markedly induced apoptosis of A549 cells through the mitochondrial- and caspase-3-dependent pathways. Consequently, compound 6l might be developed as a candidate for treating or preventing lung cancer.

Synthesis of 2-(pyridylvinyl)chromen-4-ones and their N-oxide analogs for assessment of their biological activities as anticancer agents.

2-Styrylchromones have been shown to possess a broad spectrum of biological activities. Replacing the carbon atom in 2-styrylchromones with a nitrogen atom in the benzene rings forms 2-(pyridylvinyl)chromen-4-ones (aza-2-styrylchromones). We have synthesized a series of novel 2-(pyridylvinyl)chromen-4-ones and their pyridine N-oxides to evaluate them as potential anticancer agents against human non-small-cell lung cancer cells (A549). Among the 18 synthesized molecules, compounds 18 and 8a exhibited comparable inhibitory effects to 5-fluorouracil and showed no toxicity against normal cells.

Synthesis of selenophene-based chalcone analogs and assessment of their biological activity as anticancer agents.

Selenium is an essential micronutrient that is beneficial to human health. Selenium-containing drugs have been developed as antioxidants, anti-inflammatory, and anticancer agents. However, the synthesis of selenium-containing chalcones has not been fully explored. Therefore, we report the synthesis of novel selenophene-based chalcone analogs and reveal their biological activities as anticancer agents. Among the seven synthesized molecules, compounds 6, 8, and 10 exhibited anticancer activity with IC50 values of 19.98 ± 3.38, 38.23 ± 3.30, and 46.95 ± 5.68 µM, respectively, against human colorectal adenocarcinoma (HT-29) cells. Clonogenic assays and Western blot analysis tests further confirmed that compound 6 effectively induced apoptosis in HT-29 cells through mitochondrial- and caspase-3-dependent pathways.

Improved Synthesis of Asymmetric Curcuminoids and Their Assessment as Antioxidants.

In this paper, the syntheses of twelve asymmetric curcumin analogs using Pabon's method are reported. Generally, the previously reported yields of asymmetric curcuminoids, such as 9a (53%), 9c (38%), and 9k (38%), have been moderate or low. Herein, we propose that the low yields were due to the presence of water and n-BuNH2 in the reaction media. To prove this formulated hypothesis, we have demonstrated that the yields can be improved by adding molecular sieves (MS) (4 Å) to the reaction mixture, thus reducing the interference of water. Therefore, improved yields (41-76%) were obtained, except for 9b (36.7%), 9g (34%), and 9l (39.5%). Furthermore, compounds 9b, 9d, 9e, 9f, 9g, 9h, 9i, 9j, and 9l are reported herein for the first time. The structures of these synthetic compounds were determined by spectroscopic and mass spectrometry analyses. The free radical scavenging ability of these synthetic asymmetric curcuminoids was evaluated and compared to that of the positive control butylated hydroxytoluene (BHT). Among the synthesized asymmetric curcuminoids, compounds 9a (IC50 = 37.57 ± 0.89 µM) and 9e (IC50 = 37.17 ± 1.76 µM) possessed effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities, and compounds 9h (IC50 = 11.36 ± 0.65 µM) and 9i (IC50 = 10.91 ± 0.77 µM) displayed potent 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging abilities comparable to that of curcumin (IC50 = 10.14 ± 1.04 µM). Furthermore, all the synthetic asymmetric curcuminoids were more active than BHT.