Design, Synthesis, and Biological Evaluation of Andrographolide Derivatives as Potent Hepatoprotective Agents

Abstract

Poor water solubility limits the clinical use of andrographolide and its derivatives. In an attempt to develop potent hepatoprotective drugs, a strategy was proposed to improve the aqueous solubility of andrographolide. Ten andrographolide derivatives were designed, synthesized, evaluated for aqueous solubility and in vivo hepatoprotective activity against CCl4 -induced liver injury in mice. As expected, the aqueous solubility of synthetic derivatives was effectively improved. All compounds demonstrated the effect of different degrees in improving the liver enzyme (ALT and AST) activity, especially the most promising compound 9d significantly improved liver enzyme activity, with high potency to be a new lead.

Andrographolide and analogues in cancer prevention

“…Andrographolide (C 20 H 30 O 5 ) is a colorless, crystalline, highly bitter in taste compound, possessing a lactone function. The structure of andrographolide comprises an a-alkylidene c-butyrolactone moiety, two olefin bonds Δ 8 (17) and Δ 12 (13) , and three hydroxyls at C-3, C-14, and C-19. Of the three hydroxyl groups, the one at C-14 is allylic in nature, and the others at C-3 and C-19 are secondary and primary, respectively (Figure 1).…”

“…Structure activity relationships of 19 andrographolide analogues were done, out of which a number of andrographolides showed higher cytotoxic activities than parent compound. 19-O-triphenylmethyl ether (17) and Δ 12 (13); and three hydroxyls at C-3, C-14, and C-19. © 1996-2015 analogue 18 showed higher cytotoxic activity than the potent cancer drug ellipticine (13).…”

“…Andrographolide and derivatives have been long used as hepatoprotective agent curing various types of liver damage and this property has become an important point of attraction in scientific community (1, [16][17][18][19][20]. Andrographolide has been identified as major anti-hepatotoxic component of the plant that has exerted profound protective effect in vivo against hepatotoxicity induced by CCl 4 (16,17), D-galactosamine (19), paracetamol, and ethanol (20). Andrographolide was more effective than silymarin, the standard hepatoprotective agent (1).…”

In silicoandin vitroStudies on Begomovirus Induced Andrographolide Biosynthesis Pathway inAndrographis Paniculatafor Combating Inflammation and Cancer

“…It also produces 5,7,tetramethoxyflavanone and 5‐hydroxy‐7, trimethoxyflavone, as well as several other flavonoids and polyphenols. Andrographolide, the major phytometabolite obtained from A. paniculata , is known to possess a wide range of therapeutic properties such as anti‐inflammatory, anti‐cancerous, immuno‐modulatory, [5] anti‐oxidative, anti‐viral, anti‐diabetic, anti‐thrombotic, anti‐leishmaniasis, anti‐malarial, hepatoprotective, anti‐angiogenic and is also helpful in curing various chronic diseases like leprosy, ulcer, high blood pressure, skin diseases, influenza, dysentery and bronchitis . Neoandrographolide is the other important diterpenoid that also possess anti‐inflammatory, chemosensitizing, anti‐herpes‐simplex virus and antioxidant properties.…”

Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions

“…12 Some newer semisynthetic AG derivatives were very recently reported for solubility enhancement and for likely efficacy in hepatoprotection and retardation of apoptosis. 13 We were further successful in applying different nanoparticle (NP)-engineering techniques for favorable liver-localized biological AG activity.…”