Progress in the synthesis and activity research of derivatives of Chuanxinlian lactone
The traditional Chinese medicine Androgram paniculata (Burm. F) Nees is a plant in the family Menispermaceae, which belongs to the meridians of the heart, lungs, large intestine, and bladder. It has a bitter taste and a cold nature. It has the effects of clearing heat and detoxifying, cooling blood and eliminating carbuncles. Andrographolide (molecular formula C20H30O5, structure shown in Figure 1) is a white square shaped crystal and the main extract of the medicinal plant Andrographis paniculata. Research has shown that Chuanxinlian lactone has a wide range of biological activities, such as anti infection, hepatoprotective and choleretic, anti-cancer, anti-inflammatory, antibacterial, antimalarial, immunomodulatory, anti cardiovascular and cerebrovascular disease, antiviral, etc. It is widely used in clinical practice and has significant effects. According to literature reports, Boorsma’s team first isolated a colorless crystal from Houttuynia cordata, which was later structurally identified by Gorter’s team as a lactone compound and named andrographolide. The modern extraction process of Chuanxinlian lactone often uses ultrasonic extraction method. Gao completed the asymmetric total synthesis of andrographolide for the first time in 2011 through biomimetic polyene cyclization. Chuanxinlian lactone is a bicyclic diterpenoid lactone compound, which is a trans fused semi cyclic alkane skeleton composed of two chair shaped fused hexagonal rings and a pentagonal lactone ring. It has a C-3 secondary hydroxyl group, a C-19 primary hydroxyl group, and a C-14 allyl secondary hydroxyl group, as well as two extra cyclic double bonds. These groups provide many active sites for the modification of Chuanxinlian lactone structure. Due to its poor water solubility and stability in vivo, the bioavailability of Chuanxinlian lactone is low, which limits its clinical use. Currently, it is mainly used for anti-inflammatory purposes in clinical practice. In recent years, researchers have conducted extensive structural modification and activity screening work based on the inherent property defects and relatively active structural characteristics of andrographolide, in order to discover more effective candidate drugs. This article mainly introduces the synthesis and activity research progress of Chuanxinlian lactone derivatives from four aspects: anti-tumor, anti-inflammatory, antibacterial, and antiviral.

 

Chuanxinlian lactone derivatives have a wide range of pharmacological activities, and various research groups are still committed to using them as lead compounds to synthesize a series of new Chuanxinlian lactone derivatives with better activity. At present, the modification types of Chuanxinlian lactone mainly focus on esterification, etherification, oxidation, acylation, amidation, double bond addition, oxidation, Michael addition reaction, and intramolecular cyclization reaction of hydroxyl groups. The newly synthesized derivative molecules exhibit relatively strong anti-inflammatory, anti-tumor, antibacterial, and antiviral activities. Among them, compound 69 is expected to become a candidate drug for treating inflammation due to its good water solubility and low cytotoxicity, and compound 94a is expected to be developed as a new antibacterial drug. However, the mechanism of action of derivative molecules is still largely unclear, so most active derivatives are still well applied in clinical practice. Therefore, in future derivative synthesis and activity screening work, computer-aided drug design and other methods should be applied, combined with activity verification experiments, to study and explore the targets of active derivative molecules, guide the structural modification of compounds, so as to enable more derivative molecules to enter clinical research as candidate drugs, and even develop new drugs for clinical application. In summary, over the years, researchers from various countries have never stopped studying the derivatives of paeoniflorin. Based on previous research results, they constantly seek new routes to synthesize new paeoniflorin derivatives. These studies have laid a solid foundation for the development of new drugs based on andrographolide as a lead compound.