Isoquinoline Alkaloids

Isoquinoline alkaloids are an extremely large group of alkaloids mostly occurring in higher plants, but few groups are also isoquinolinoid marine alkaloids. Isoquinoline nucleus is the basic structural feature (Figure 1). Isoquinoline alkaloids are not a structurally homogenous group. Based on different degrees of oxygenation, and intramolecular rearrangements, their distribution, and the presence of additional rings connected to the main system, they may be divided into eight subgroups: benzylisoquinoline, aporphine, protoberberine, benzo[c]phenanthridine, protopine, phthalideisoquinoline, morphinan, and emetine alkaloids. Among the listed subgroups, the protoberberines are the largest group-they constitute 25% of all elucidated structures of isoquinoline alkaloids, which makes them the most widespread secondary metabolites containing nitrogen among natural products. Isoquinoline alkaloids have long been of great importance to humans because of their medicinal value and structural differences.

Figure 1. Basic structure of the isoquinoline nucleus.

Bioactivities of isoquinoline alkaloids

Isoquinoline alkaloids make a large family of natural products showing a wide range of structural diversity and biological activity. These bioactivities are mainly expressed in antitumor, antibacterial, antifungal, antiviral, and anti-inflammatory aspects.

• Antitumor activities

Isoquinoline alkaloids show antitumor effects on various tumor cells. Numerous studies have investigated and reported antitumor mechanism of known and new isolated isoquinoline alkaloids. For example, Berberine inhibited cancer cell proliferation via several mechanisms of action, such as the positive regulation of reactive oxygen species and the apoptotic pathway as well as suppressed cancer metastasis by stopping transferase activity.

• Antibacterial and antifungal activities

Most of the isoquinoline alkaloids have excellent antibacterial and antifungal activities. Take berberine and oxoaporphine alkaloid isomoschatoline as an example. Berberine exhibited antibacterial activity against Candida albicans. Moreover, berberine also effectively protected mice infected with Salmonella typhimurium. And the oxoaporphine alkaloid isomoschatoline ^[1] had an absorption profile with bands at 600-700 nm, was positive for singlet oxygen production and exhibited photodynamic antimicrobial activity against both gram-positive and gram-negative bacteria and some Candida ssp. yeast strains at sub-inhibitory concentrations.

• Antiviral activity

Isoquinoline alkaloids have antiviral pharmacological activity as the predominant plant secondary metabolites. It has been shown that berberine reduces virus replication and targets specifc interactions between the virus and its host. For example, berberine can insert into DNA and inhibit DNA synthesis and reverse transcriptase activity. It also inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodefciency virus (HIV). Corydine ^[2] and norisoboldine ^[3], aporphine alkaloids from Croton echinocarpus leaves, similarly displayed significant in vitro anti-HIV potential. The latter compound more potently inhibited HIV-1 reverse transcriptase enzyme activity.

• Anti-inflammatory activity

Isoquinoline alkaloids are the most studied classes for anti-inflammatory activity. The major isoquinoline alkaloid such as berberine and norisoboldine have significant anti-inflammatory activity and can be used for the treatment of inflammation and other related diseases through different mechanisms of action.

Common isoquinoline alkaloids

Naturally occurring berberine, palmatine and synthetic coralyne are the most widely distributed natural alkaloids in the isoquinoline family, and they are also the main active ingredients in some Chinese herbal medicines, such as Rhizoma coptidis and Cortex phellodendri. They are found in many plants, such as Chinese herb huanglian (Coptis chinesis), goldensal (Hydrastis canadensis), Turkish berberis and the roots of species belonging to the Malagasy genus Burasaia, Menispermaceae. Berberine and palmatine have the same tetracyclic structure but with different substituents on the benzene ring (ring A, Figure 2), methylenedioxy for berberine and dimethoxy for palmatine. Unlike berberine and palmatine with buckled structure (due to partial saturation in the ring B, Figure 2), coralyne is a planar molecule. Statistically, these isoquinoline alkaloids have a long history of use in medicine and have been used extensively to treat a variety of diseases.

Figure 2. Chemical structures of (a) berberine, (b) palmatine and (c) coralyne.

What we offer

As a supplier of alkaloids, Alfa Chemistry has always shown great interest in the latest developments in isoquinoline alkaloids. Alfa Chemistry is committed to providing a wide range of isoquinoline alkaloids. If you do not find what you need, please contact us. We also offer product customization according to customer's detailed requirements.

References

1. Dong, Z. B.; et al. Screening for anti-inflammatory components from Corydalis bungeana Turcz. based on macrophage binding combined with HPLC. BMC Complem Altern Med. 2015; 15: 363.
2. Han, A. R.; et al. Isoquinoline alkaloids from Corydalis pallida. Chem Nat Compds. 2018, 54: 1020-1022.
3. Naz, I.; et al. Cis- and trans-protopinium, a novel nematicide, for the eco-friendly management of root-knot nematodes. Crop Prot. 2016, 81: 138-144.