Biomolecules (Jun 2022)

Alkaloids of <i>Dicranostigma franchetianum</i> (Papaveraceae) and Berberine Derivatives as a New Class of Antimycobacterial Agents

  • Viriyanata Wijaya,
  • Ondřej Janďourek,
  • Jana Křoustková,
  • Kateřina Hradiská-Breiterová,
  • Jan Korábečný,
  • Kateřina Sobolová,
  • Eliška Kohelová,
  • Anna Hošťálková,
  • Klára Konečná,
  • Marcela Šafratová,
  • Rudolf Vrabec,
  • Jiří Kuneš,
  • Lubomír Opletal,
  • Jakub Chlebek,
  • Lucie Cahlíková

DOI
https://doi.org/10.3390/biom12060844
Journal volume & issue
Vol. 12, no. 6
p. 844

Abstract

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Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis. 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 (NPs). In order to search for new antiTB drugs, the detailed phytochemical study of the whole Dicranostigma franchetianum plant was performed isolating wide spectrum of isoquinoline alkaloids (IAs). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. Alkaloids were screened against Mycobacterium tuberculosis H37Ra and four other mycobacterial strains (M. aurum, M. avium, M. kansasii, and M. smegmatis). Alkaloids 3 and 5 showed moderate antimycobacterial activity against all tested strains (MICs 15.625–31.25 µg/mL). Furthermore, ten semisynthetic berberine (16a–16k) derivatives were developed and tested for antimycobacterial activity. In general, the derivatization of berberine was connected with a significant increase in antimycobacterial activity against all tested strains (MICs 0.39–7.81 μg/mL). Two derivatives (16e, 16k) were identified as compounds with micromolar MICs against M. tuberculosis H37Ra (MIC 2.96 and 2.78 µM). All compounds were also evaluated for their in vitro hepatotoxicity on a hepatocellular carcinoma cell line (HepG2), exerting lower cytotoxicity profile than their MIC values, thereby potentially reaching an effective concentration without revealing toxic side effects.

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