Short Lecture “Isoquinoline alkaloids and their derivatives as a new class of antimycobacterial drugs”

Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the Global Tuberculosis Report 2021, issued by the World Health Organization (WHO), the latent form of Mtb has infected about a quarter of the worldʼs population, but only a small part (5 – 10%) will develop this bacterial disease [1]. The increasing incidence of multidrug-resistant (MDR), and extensively drug-resistant (XDR) strains has created a need for new antiTB agents with new chemical scaffolds to combat the disease. Thus, the key question is: how to search for new antiTB and where to look for them? One of the possibilities is to search among natural products.

In order to search for new antiTB drug, we screened isolated alkaloids in our lab within previous phytochemical studies against Mtb H37Ra and four other mycobacterial strains (M. aurum, M. avium, M. kansasii, and M. smegmatis). In order to expand portfolio of tested compounds several series of semisynthetic derivatives of selected alkaloids (e.g. berberine, galanthamine, haemanthamine and others) were developed and tested. Derivatization of berberine in position C-9 was connected with a significant increase in antimycobacterial activity against all tested strains (MICs 0.39 – 7.81 µg/mL). Derivatization of galanthamine in position C-6 was connected with increase of activity against Mtb H37Ra (MICs 1.56 – 15.625 µg/mL).

The most active compounds were also evaluated for their in vitro hepatotoxicity on a hepatocellular carcinoma cell line (HepG2), exerting lower IC₅₀ values than their MIC values, further corroborating their potential as potent and safe antimycobacterial agents.

• Reference

• 1 Global tuberculosis report 2021,. https://www.who.int/publications/i/item/9789240037021

Publication History

Article published online:
12 December 2022