Synthesis of Alkaloid Sinomenine Derivatives Containing a Pyrimidine Substituent in Ring A

Finke, Anastasiya O.; Карцев, В. Г.; Шульц, Э. Э.

doi:10.1007/s10593-021-03003-4

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Moreover, many studies have showed that structural modification is effective to improve bioactivity and to reduce side effect. Several structural modifications of SIN have been attempted in many research groups with great success [16–18] . Figure 1 summarizes the structure and important modification sites of SIN.…”

Section: Introductionmentioning

confidence: 99%

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Sinomenine Derivatives: Synthesis, Antitumor Activity, and Apoptotic Induction in MCF‐7 Cells via IL‐6/PI3K/Akt/NF‐κB Signaling Pathway

et al. 2022

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Natural products have been widely considered as an important resource for new drugs or lead compounds. Sinomenine (SIN) and its derivatives exert antitumor activity via regulation of inflammatory mediators. For these reasons we synthesized three series of SIN derivatives (compounds 4 a-i, 7 a-c and 11 a-c) as antitumor agents from this natural product. All compounds were prepared by modification at the C1 and C4 positions of the A ring, the C4 position of the A ring, and the C6 and C7 positions of the C ring, respectively. All the derivatives were subjected to in vitro antitumor activity against HeLa, A549, HepG-2, MCF-7 and HT-29 cell lines. To observe the apoptotic induction of SIN derivatives and its mechanism, fluorescent staining and western blot assays were carried out for active compound against MCF-7. Based on the screening results, most of the SIN derivatives showed better antitumor activity than SIN. Some of them were found to possess broad-spectrum antitumor activity. Most notably, 11 c exhibited obvious antitumor activity in both cell lines with IC 50 values less than 11 μM. Besides, 11 c induced apoptosis of MCF-7 in a dose-dependent manner. Western blot assay demonstrated that 11 c inhibited IL-6-mediated activation of PI3K/Akt pathway. A docking study revealed that 11 c had stronger binding interaction with the residues of IL-6 than SIN. All these results indicate that 11 c may be a potential anti-breast cancer agent by directly targeting IL-6.

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Section: Introductionmentioning

confidence: 99%

“…Several structural modifications of SIN have been attempted in many research groups with great success. [16][17][18] Figure 1 summarizes the structure and important modification sites of SIN. Among them, structural modification on C1 and C4 of SIN had been found particularly suitable for antitumor activity.…”

Section: Introductionmentioning

confidence: 99%