Searching for new cytotoxic agents based on chromen-4-one and chromane-2,4-dione scaffolds

Abstract

Cancer is a major cause of death worldwide and novel anticancer agents for its better management are much needed. Benzopyrone-based compounds, such as chromones, possess several distinctive chemical and biological properties, of which the cytotoxicity against cancer cells seems to be prominent. In this study, two series of compounds based on chromen-4-one (3-10) and chromane-2,4-dione (11-18) scaffolds were synthesized in moderate/high yields and evaluated for cytotoxicity against HL-60, MOLT-4, and MCF-7 cancer cells using MTT assay. In general, the compounds exhibited moderate cytotoxic effects against the cancer cell lines, among which, a superior potency could be observed against MOLT-4 cells. Chroman-2,4-dione (11-18) derivatives had overall higher potencies compared to their chromen-4-one (3-10) counterparts. Compound 13 displayed the lowest IC 50 values against HL-60 (IC 50 , 42.0 ± 2.7 μM) and MOLT-4 cell lines (IC 50 , 24.4 ± 2.6 μM), while derivative 11 showed the highest activity against MCF-7 cells (IC 50 , 68.4 ± 3.9 μM). In conclusion, this study provides important information on the cytotoxic effects of chromone derivatives. Benzochroman-2,4-dione has been identified as a promising scaffold, which its potency can be modulated by tailored synthesis with the aim of finding novel and dissimilar anticancer compounds.

Quantitative Structure–Cytotoxicity Relationship of 2-Arylazolylchromones and 2-Triazolylchromones

“…Figure 1. The structure of the eight 2-arylazolylchromones [1][2][3][4][5][6][7][8] and the twelve 2-triazolylchromones [9][10][11][12][13][14][15][16][17][18][19][20] investigated in this study.…”

“…4. Top six chemical descriptors that showed higher correlation with cytotoxicity of eight 2-arylazolylchromones[1][2][3][4][5][6][7][8] and twelve 2triazolylchromones[9][10][11][12][13][14][15][16][17][18][19][20] against OSCC cells. The mean negative log CC 50 values (T) against tumor cells were plotted.…”

“…Top six chemical descriptors were: SaaN (topological shape and electric state), P_VSA_e_3 (topological shape and electric state), SlogP_VSA1 (topological size and lipophilicity), BCUT_PEOE_1 (topological shape and partial charges), T(N..N) (topological shape and size) and nBnz (topological shape and size).Figure5. Top six chemical descriptors that showed higher correlation with cytotoxicity of eight 2-arylazolylchromones[1][2][3][4][5][6][7][8] and twelve 2triazolylchromones[9][10][11][12][13][14][15][16][17][18][19][20] against normal oral cells. The mean negative log CC 50 values (N) against normal cells were plotted.…”

Chromones: Privileged scaffold in anticancer drug discovery

“…While 7-methoxy-2-(4-morpholinyl)-4H-1-benzop yran-4-one has highest tumor specificity and cytotoxicity was found to be correlated with molecular shape. SAR analysis concluded during cytotoxicity studies of some synthesized chroman-2,4-dione derivatives against leukemia and breast cancer cells are (Gaspar et al, 2019):…”

Synthesis and Evaluation of Anticancer Potential of Novel Benzopyran Derivatives Using MTT and in vitro Scratch Assays

“…In recent decades, benzopyrans have attracted significant attention due to their remarkable chemical and biological characteristics [1]. Benzopyrans are the oxygenated fused heterocyclic nucleus containing compounds that are structurally elucidated as 1-benzopyran-2(2H)-one) and are highly persistent in natural and bioactive moieties [2,3].…”