dc.contributor.author | Wijaya, Viriyanata | |
dc.date.accessioned | 2023-04-20T02:39:39Z | |
dc.date.available | 2023-04-20T02:39:39Z | |
dc.date.issued | 2022-06-17 | |
dc.identifier.issn | 2218-273X | |
dc.identifier.uri | http://repository.unmul.ac.id/handle/123456789/51812 | |
dc.description.abstract | Abstract: 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. | en_US |
dc.description.sponsorship | This project was supported by Charles University grants (SVV UK 260 548, Progress/UK
Q42), by project, “Modernization and Extension of the Doctoral Study Field of Pharmacognosy and Toxicity of Natural Products” in the study program Pharmacy (reg. No. CZ.02.2.69/0.0/0.0/16_018/0002736),
and by Ministry of Health of the Czech Republic (project No. NU21-05-00446). | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.relation.ispartofseries | Natural and Bio-inspired Molecules; | |
dc.subject | Dicranostigma franchetianum; Papaveraceae; isoquinoline alkaloids; berberine; antimy cobacterial activity; cytotoxicity | en_US |
dc.title | Alkaloids of Dicranostigma franchetianum (Papaveraceae) and Berberine Derivatives as a New Class of Antimycobacterial Agents | en_US |
dc.type | Article | en_US |