Design, Synthesis and Preliminary Biological Evaluation of Benzylsulfone Coumarin Derivatives as Anti-Cancer Agents

Abstract

In this work, a series of benzylsulfone coumarin derivatives 5a–5o were synthesized and characterized. Kinase inhibitory activity assay indicated that most of the compounds showed considerable activity against PI3K. Anti-tumor activity studies of the active compounds were also carried out in vitro on the Hela, HepG2, H1299, HCT-116, and MCF-7 tumor cell lines by MTS assay. The structure–activity relationships (SARs) of these compounds were analyzed in detail. Compound 5h exhibited the most potent activities against the mentioned cell lines with IC50 values ranging from 18.12 to 32.60 μM, followed by 5m with IC50 values of 29.30–42.14 μM. Furthermore, 5h and 5m clearly retarded the migration of Hela cells in vitro. Next, an in silico molecular docking study was conducted to evaluate the binding models of 5h and 5m towards PI3Kα and PI3Kβ. Collectively, the above findings suggested that compounds 5h and 5m might be promising PI3K inhibitors deserving further investigation for cancer treatment.

Synthesis and biological activities of novel trifluoromethylpyridine amide derivatives containing sulfur moieties

“…It can be found in many secondary metabolites in living organisms, and exits also in many bio-active compounds ( Fig. 1) with broaden biological activities, [7][8][9][10][11][12][13][14] especially using for anticancer, [15][16][17][18] anti-HIV, 19,20 and treating acid-related disorder, 21 and also using for the inhibitors of topoisomerase 1, 22 anhydrase II, 23 mutated B-Raf, 24,25 cyclooxygenase-2. 26,27 Particularly, compounds containing thioether, sulfone or sulfoxide moieties could exhibit signicantly anti-bacterial, [28][29][30][31][32] anti-fungal, 33,34 herbicidal 35 and insecticidal 36,37 activities for crop protection.…”

A Review on Anti-Tumor Mechanisms of Coumarins

“…Wang (15) synthesized 15 kinds of benzylsulfone coumarin derivatives (5a-5o) and found that 3-[(4-fluorobenzyl)sulfonyl]-6nitro-2h-chromen-2-one (5h) and 6-bromo-3-[(4-fluorobenzyl) sulfonyl] -2h-chromen-2-one (5m) exibited the strongest inhibitory activities against PI3K, with inhibition rates of 50.3% and 50.8% at 20 mM respectively in vitro experiments. In addition, 5h and 5m had broad-spectrum anti-tumor activities, with the IC50 values for 5 tumor cell lines (Hela, HepG2, H1299, hct-116, and McF-7) ranging from (18.1-32.6) mM and (29.3-42.1) mM, respectively.…”

Design, synthesis and anticancer activity studies of 3-(coumarin-3-yl)-acrolein derivatives: Evidenced by integrating network pharmacology and vitro assay

“…Its mechanism of promoting autophagy by inhibiting PI3K/AKT/mTOR signaling pathway was revealed ( Yao et al, 2020 ). Wang et al (2019) synthesized a series of benzylsulfone coumarin derivatives and identified compound C ( Figure 1C ) as a promising PI3K inhibitor, which displayed good antitumor activities against Hela cells by retarding cell migration. Meanwhile, low toxicity and side effects have been constantly found in a lot of coumarin derivatives as medicinal candidates.…”