Design, Synthesis, Biological Evaluation and Silico Prediction of Novel Sinomenine Derivatives

Abstract

Sinomenine is a morphinan alkaloid with a variety of biological activities. Its derivatives have shown significant cytotoxic activity against different cancer cell lines in many studies. In this study, two series of sinomenine derivatives were designed and synthesized by modifying the active positions C1 and C4 on the A ring of sinomenine. Twenty-three compounds were synthesized and characterized by spectroscopy (IR, 1H-NMR, 13C-NMR, and HRMS). They were further evaluated for their cytotoxic activity against five cancer cell lines, MCF-7, Hela, HepG2, SW480 and A549, and a normal cell line, Hek293, using MTT and CCK8 methods. The chlorine-containing compounds exhibited significant cytotoxic activity compared to the nucleus structure of sinomenine. Furthermore, we searched for cancer-related core targets and verified their interaction with derivatives through molecular docking. The chlorine-containing compounds 5g, 5i, 5j, 6a, 6d, 6e, and 6g exhibited the best against four core targets AKT1, EGFR, HARS and KARS. The molecular docking results were consistent with the cytotoxic results. Overall, results indicate that chlorine-containing derivatives might be a promising lead for the development of new anticancer agents.

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…In 2021, researchers reported that the highly active compound 6d ( 8 ) exhibited notable cytotoxicity through the PI3K/AKT and MAPK signaling pathways, with IC 50 values ranging from 3.46 µM to 11.51 µM against various cancer cell lines (MCF-7, HeLa, HepG2, SW480, and A549). However, compound 6d demonstrated less selectivity towards the normal cell line Hek293, with an IC 50 of 3.46 µM [ 66 ]. G.H.…”

A novel “turn on” fluorescence probe based on a caffeic acid skeleton for detecting Al3+ and bioimaging application

“…Then HeLa cells were placed in 96-well plates with a total of 6500 cells per well. [23][24][25] The treated HeLa cells were incubated with various concentrations of probe HAM (ranging from 0 to 100 mM) for 24 h. Following incubation, CCK-8 solution was supplemented and HeLa cells were further incubated for 4 h. The cell viability was determined according to the optical density of the experimental group. HeLa cells were rst incubated with probe HAM in 96-well plates for 24 h. The selected HeLa cells were incubated with probe HAM (10 mM) for 30 min.…”

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

“…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.…”

“…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.…”