Natural products and drug discovery

Newman, David J.; Phil, D

doi:10.1093/nsr/nwac206

Cited by 51 publications

(34 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, several strategies have been developed to enhance the anti-tumor effects of ART treatment. These include the design of new artemisinin derivatives, such as Artesunate-loaded nanoparticles [48], the conjugation of Artesunate with aptamers [49] and chemically modified artemisinin derivatives [42,50]. Another possibility lies in the combination of ART with various established drugs, including the angiotensin converting enzyme (ACE) inhibitor Captopril [51], the Ras inhibitor Farnesylthiosalicylic acid [52] and the heme precursor 5-Aminolevulinic acid (5-ALA) [23].…”

Section: Artesunate Induced Heterogeneous Anti-tumor Effects In Heter...mentioning

confidence: 99%

Anti-Cancer Effects of Artesunate in Human 3D Tumor Models of Different Complexity

Niederreiter

Klein

Arndt

et al. 2023

IJMS

View full text Add to dashboard Cite

The anti-malaria drug Artesunate (ART) shows strong anti-cancer effects in vitro; however, it shows only marginal treatment results in clinical cancer studies. In this study, ART was tested in preclinical 3D cancer models of increasing complexity using clinically relevant peak plasma concentrations to obtain further information for translation into clinical use. ART reduced cell viability in HCT-116 and HT-29 derived cancer spheroids (p < 0.001). HCT-116 spheroids responded dose-dependently, while HT-29 spheroids were affected more strongly by ART than by cytostatics (p < 0.001). HCT-116 spheroids were chemo-sensitized by ART (p < 0.001). In patient-derived cancer spheroids (PDCS), ART led to inhibition of cell viability in 84.62% of the 39 samples tested, with a mean inhibitory effect of 13.87%. Viability reduction of ART was 2-fold weaker than cytostatic monotherapies (p = 0.028). Meanwhile, tumor-stimulation of up to 16.30% was observed in six (15.38%) PDCS-models. In 15 PDCS samples, ART modulated chemotherapies in combined testing, eight of which showed chemo-stimulation (maximum of 36.90%) and seven chemo-inhibition (up to 16.95%). These results demonstrate that ART’s anti-cancer efficacy depends on the complexity of the tumor model used. This emphasizes that cancer treatment with ART should be evaluated before treatment of the individual patient to ensure its benefits and prevent unwanted effects.

show abstract

Section: Artesunate Induced Heterogeneous Anti-tumor Effects In Heter...mentioning

confidence: 99%

Anti-Cancer Effects of Artesunate in Human 3D Tumor Models of Different Complexity

Niederreiter

Klein

Arndt

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The utilization of natural products sourced from plants, microorganisms, and marine organisms is a vital component of drug discovery and development. [1][2][3] However, some natural products often require structural modification to address deficiencies such as structural complexity, suboptimal biological activity, and low isolation yields. 4 Structural simplification and optimization of natural products have been identified as an effective strategy for overcoming these limitations and identifying potential pharmaceutical leads.…”

Section: Introductionmentioning

confidence: 99%

Practical synthesis and divergent optimization of halichonine B for the discovery of novel pharmaceutical leads

Hu,

Wang,

Sun

et al. 2024

Org. Chem. Front.

View full text Add to dashboard Cite

show abstract

“…The situation is further aggravated by the potential development of mutants that are drug resistant, thus limiting drug efficacy (1)(2)(3)(4) Natural products represent a rich source of diverse, new, and inexpensive chemical starting points for drug discovery in the area of antivirals and serve as an outstanding source of biodiversity for the discovery of novel compounds. Indeed, approximately 65% of successfully approved drugs are either natural products or derivatives (5). Many natural products derived from microbes have been reported to have robust antiviral activity, with anti-hepatitis, anti-herpes simplex, anti-HIV, anti-influenza, anti-respiratory syncytial virus, and anti-SARS-CoV-2 properties (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Establishment of a screening platform based on human coronavirus OC43 for the identification of microbial natural products with antiviral activity

Martínez-Arribas

Annang

Diaz-Gonzalez

et al. 2023

Preprint

View full text Add to dashboard Cite

Human coronaviruses (HCoVs) cause respiratory tract infections and are of great importance due to the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Human betacoronavirus OC43 (HCoV-OC43) is an adequate surrogate for SARS-CoV-2 because it infects the human respiratory system, presents a comparable biology, and is transmitted in a similar way. Its use is advantageous since it only requires biosafety level (BSL)-2 infrastructure which minimizes costs and biosafety associated limitations. In this report, we describe a high-throughput screening (HTS) platform to identify compounds that inhibit the propagation of HCoV-OC43. Optimization of assays based on inhibition of the cytopathic effect and virus immunodetection with a specific antibody, has provided a robust methodology for the screening of a selection of microbial natural product extracts from the Fundación MEDINA collection. Using this approach, a subset of 1280 extracts has been explored. Of these, upon hit confirmation and early LC-MS dereplication, 10 extracts were identified that contain potential new compounds. In addition, we report on the novel antiviral activity of some previously described natural products whose presence in bioactive extracts was confirmed by LC/MS analysis.IMPORTANCEThe COVID-19 pandemic has revealed the lack of effective treatments against betacoronaviruses and the urgent need for new broad-spectrum antivirals. Natural products are a valuable source of bioactive compounds with pharmaceutical potential that may lead to the discovery of new antiviral agents. Specifically, compared to conventional synthetic molecules, microbial natural extracts possess a unique and vast chemical diversity and are amenable to large-scale production. The implementation of a high-throughput screening platform using the betacoronavirus OC43 in a human cell line infection model has provided proof of concept of the approach and has allowed for the rapid and efficient evaluation of 1280 microbial extracts. The identification of several active compounds validates the potential of the platform for the search for new compounds with antiviral capacity.

show abstract

Natural products and drug discovery

Cited by 51 publications

References 82 publications

Anti-Cancer Effects of Artesunate in Human 3D Tumor Models of Different Complexity

Anti-Cancer Effects of Artesunate in Human 3D Tumor Models of Different Complexity

Practical synthesis and divergent optimization of halichonine B for the discovery of novel pharmaceutical leads

Establishment of a screening platform based on human coronavirus OC43 for the identification of microbial natural products with antiviral activity

Contact Info

Product

Resources

About