The Chemistry and Biology of Alkannin, Shikonin, and Related Naphthazarin Natural Products

Abstract

Wound healing properties of plant extracts that contain the naphthoquinone natural products alkannin (1) and shikonin (2) have been known for many centuries. More recently, the biological properties of 1, 2, and related derivatives have been demonstrated experimentally, and their production both by cell cultures and chemical synthesis has been studied extensively.

Preparative isolation and purification of alkannin/shikonin derivatives from natural products by high‐speed counter‐current chromatography

“…Monomeric alkannin and shikonin derivatives, mainly esters from the side chain hydroxyl group (Tables 1 and 2), have been identified in the roots of several plants of the Boraginaceae family, especially Alkanna tinctoria, Lithospermum erythrorhizon and Arnebia euchroma. The chiral pair A/S are potent pharmaceutical substances with a well-established and wide spectrum of wound healing, antimicrobial, anti-inflammatory, anticancer, antithrombotic and antioxidant biological activity (Papageorgiou, 1980;Papageorgiou et al, 1999Papageorgiou et al, , 2006. These comprise the active ingredients of several pharmaceutical and cosmetic preparations.…”

“…This method is expensive and cannot be effectively utilized for industrial scale. Recently, biotechnological methods have been developed (plant tissue cultures) for the production of A/S derivatives from Lithospermum erythrorhizon and Alkanna tinctoria roots (Papageorgiou et al, 1999. In that case, A/S and their derivatives are produced and after their isolation the same procedure as in natural products ( Fig.…”

“…Structures of characteristic monomeric, dimeric and trimeric A/S derivatives identified [Papageorgiou, 1980;Papageorgiou et al, 1999Papageorgiou et al, , 2006Assimopoulou et al, 2006Assimopoulou et al, , 2008 Monomeric A/S derivatives Dimeric A/S derivatives Trimeric A/S derivatives and other metabolites (Papageorgiou et al, 2002;Assimopoulou and Papageorgiou, 2004a,b;Spyros et al, 2005;Assimopoulou et al, 2008), and thus need further purification. This step is crucial for biological experiments of A/S derivatives, since many papers report the biological evaluation of commercial and not purified A/S samples.…”

“…Table 2. Characteristic monomeric, dimeric and trimeric A/S derivatives identified [Papageorgiou, 1980;Papageorgiou et al, 1999Papageorgiou et al, , 2006Assimopoulou et al, 2006Assimopoulou et al, , 2008 Additionally, the purity of fractions separated by HSCCC was compared with those obtained by the traditionally used method, column chromatography, using as stationary phases silica gel and Sephadex LH-20, a beaded cross-linked dextran gel used for the size exclusion separation of small organic molecules.…”

Synthesis and biological evaluation of substituted naphthoquinone derivatives as potent antimycobacterial agents

“…1,4-Naphthoquinone structure is common in various natural products 8 and is found to exhibit an interesting range of pharmacological properties including antibacterial, 9,10 antiviral, 11 trypanocidal, 12 anticancer, 13 antimalarial 14,15 and antifungal 16 activities. Other quinone-related scaffolds such as 2-H-pyran-3(6H)-one derivatives 17 and 2,3-dideoxyhexenopyranosides 18 are also known for their biological activity against Gram positive bacteria such as Staphylococcus aureus and M. tuberculosis.…”