Natural Products as Pharmaceuticals and Sources for Lead Structures**Note: This chapter reflects the opinions of the authors, not necessarily those of the US Government

Newman, David J.; Cragg, Gordon M.; Kingston, David G. I.

doi:10.1016/b978-0-12-417205-0.00005-5

Cited by 20 publications

(3 citation statements)

References 276 publications

(180 reference statements)

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“…Unlike compounds from chemical libraries, potent natural products often already cover the physicochemical property space to achieve antibacterial activity (Grabowski & Schneider, 2007 ; Newman et al , 2015 ; Wright, 2017 ), making them a great starting point for identifying novel antibiotics. Although these compounds are evolutionarily optimised to achieve such potential, it should be mentioned that they frequently lack the ADME profiles required for antibiotic development and as such require improvement via synthetic modifications.…”

Section: The Need For New Antibioticsmentioning

confidence: 99%

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

et al. 2022

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Antibacterial resistance is one of the greatest threats to human health. The development of new therapeutics against bacterial pathogens has slowed drastically since the approvals of the first antibiotics in the early and mid-20 th century. Most of the currently investigated drug leads are modifications of approved antibacterials, many of which are derived from natural products. In this review, we highlight the challenges, advancements and current standing of the clinical and preclinical antibacterial research pipeline. Additionally, we present novel strategies for rejuvenating the discovery process and advocate for renewed and enthusiastic investment in the antibacterial discovery pipeline.

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Section: The Need For New Antibioticsmentioning

confidence: 99%

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

et al. 2022

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“…Since current therapeutic agents can cause systemic toxicity and cancer cell resistance, compounds from natural products represent promising alternative therapeutics for cancer management and treatment. Many clinically active anticancer agents are derived from plant source, including paclitaxel, etoposide, teniposide, vinblastine, vincristine, camptothecin, ingenol mebutate, omacetaxine, mepesuccinate, and combretastatin A4 phosphate [64].…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Effects of Chlorophyllides in Ethanol Crude Extracts from Plant Leaves

Wang

Yang

Huang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Chlorophyllide (chlide) is a natural catabolic product of chlorophyll (Chl), produced through the activity of chlorophyllase (chlase). The growth inhibitory and antioxidant effects of chlide from different plant leaf extracts have not been reported. The aim of this study is to demonstrate that chlide in crude extracts from leaves has the potential to exert cytotoxic effects on cancer cell lines. The potential inhibitory and antioxidant effects of chlide in crude extracts from 10 plant leaves on breast cancer cells (MCF7 and MDA-MB-231), hepatocellular carcinoma cells (Hep G2), colorectal adenocarcinoma cells (Caco2), and glioblastoma cells (U-118 MG) were studied using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. The results of the MTT assay showed that chlide in crude extracts from sweet potato were the most effective against all cancer cell lines tested. U-118 MG cells were the most sensitive, while Caco2 cells were the most resistant to the tested crude extracts. The cytotoxic effects of chlide and Chl in crude extracts from sweet potato and of commercial chlorophyllin (Cu-chlin), in descending order, were as follows: chlide > Chl > Cu-chlin. Notably, the IC50 of sweet potato in U-118 MG cells was 45.65 μg/mL while those of Chl and Cu-chlin exceeded 200 μg/mL. In the DPPH assay, low concentrations (100 μg/mL) of chlide and Cu-chlin from crude extracts of sweet potato presented very similar radical scavenging activity to vitamin B2. The concentration of chlide was negatively correlated with DPPH activity. The current study was the first to demonstrate that chlide in crude extracts from leaves have potential cytotoxicity in cancer cell lines. Synergism between chlide and other compounds from leaf crude extracts may contribute to its cytotoxicity.

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“…Evidence for the use of Artemisia spp. extracts in traditional medicine dates back to 340 common era (CE) in Chinese culture (28) and is well-known across African cultures (29). Artesunate has been shown to have anti-viral properties against double-and single-stranded deoxyribose nucleic acid (DNA) and ribonucleic acid (RNA) viruses including human cytomegalovirus (HCMV), herpes viruses, hepatitis B and C, and related viruses (including Epstein-Barr virus) (30), providing the premise for deployment against SARS-CoV-2.…”

Section: Artesunatementioning

confidence: 99%

The COVID-19 Treatment Landscape: A South African Perspective on a Race Against Time

et al. 2021

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The pandemic caused by SARS-CoV-2 has infected more than 94 million people worldwide (as of 17 January 2020). Severe disease is believed to be secondary to the cytokine release syndrome (CRS or “cytokine storm”) which causes local tissue damage as well as multi-organ dysfunction and thrombotic complications. Due to the high mortality rates in patients receiving invasive ventilation, practice has changed from “early-intubation” for acute respiratory distress syndrome (ARDS) to a trial of non-invasive ventilation (NIV) or high flow nasal cannula (HFNC) oxygen. Reports indicating the benefit of NIV and HFNC have been encouraging and have led to more than 20,000 such devices being manufactured and ready for roll-out in South Africa (SA) as of July 2020. The need to identify drugs with clear clinical benefits has led to an array of clinical trials, most of which are repurposing drugs for COVID-19. The treatment landscape reflects the need to target both the virus and its effects such as the CRS and thrombotic complications. Conflicting results have the potential to confuse the implementation of coordinated treatment strategies and guidelines. The purpose of this review is to address pertinent areas in the current literature on the available medical treatment options for COVID-19. Remdesivir, tocilizumab, and dexamethasone are some of the treatment options that have shown the most promise, but further randomized trials are required to particularly address timing and dosages to confidently create standardized protocols. For the SA population, two healthcare sectors exist. In the private sector, patients with medical insurance may have greater access to a wider range of treatment options than those in the public sector. The latter serves >80% of the population, and resource constraints require the identification of drugs with the most cost-effective use for the greatest number of affected patients.

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Natural Products as Pharmaceuticals and Sources for Lead Structures**Note: This chapter reflects the opinions of the authors, not necessarily those of the US Government

Cited by 20 publications

References 276 publications

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

Cytotoxic Effects of Chlorophyllides in Ethanol Crude Extracts from Plant Leaves

The COVID-19 Treatment Landscape: A South African Perspective on a Race Against Time

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