The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

Cheuka, Peter Mubanga; Mayoka, Godfrey; Mutai, Peggoty; Chibale, Kelly

doi:10.3390/molecules22010058

Cited by 178 publications

(111 citation statements)

References 233 publications

(279 reference statements)

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“…Vice versa, poor people affected by NTDs are in want of affordable drugs, which could, however, arise from tapping into natural resources. Many natural product derived drug candidates, active against various NTDs, have emerged . In addition, natural products constitute sustainable, cheap materials.…”

Section: Introductioncontrasting

confidence: 57%

“…Due to the climate change, further regions of the world will likely be affected by these parasitic diseases in the future . There are only a few drugs available against NTDs because big pharma is reluctant to develop new and more potent drugs against diseases that mainly poor people suffer from . Vice versa, poor people affected by NTDs are in want of affordable drugs, which could, however, arise from tapping into natural resources.…”

Section: Introductionmentioning

confidence: 99%

“…[2] There are only a few drugs available against NTDs because big pharma is reluctant to develop new and more potent drugs against diseases that mainly poor people suffer from. [3] Vice versa, poor people affected by NTDs are in want of affordable drugs, which could, however, arise from tapping into natural resources. Many natural product derived drug candidates, active against various NTDs, have emerged.…”

Section: Introductionmentioning

confidence: 99%

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New Antiparasitic Bis‐Naphthoquinone Derivatives

Jentzsch

Koko

Nasr

et al. 2020

Chemistry & Biodiversity

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A series of bis‐naphthoquinone derivatives prepared by condensation of aryl aldehydes with lawsone were tested for antiparasitic activities against Toxoplasma gondii and Trypanosoma brucei parasites. Monofluorophenyl derivative 1a, 3,4‐difluorophenyl analog 1c and furyl compound 1l exhibited significant activity against T. gondii cells and appear to be new promising drug candidates against this parasite. The 3,4,5‐trifluorophenyl derivative 1g and the isovanillyl derivative 1j displayed selective activity against Leishmania major amastigotes.

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Section: Introductioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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New Antiparasitic Bis‐Naphthoquinone Derivatives

Jentzsch

Koko

Nasr

et al. 2020

Chemistry & Biodiversity

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“…In doing so, it will identify potential pipelines for target discovery and validation which could inform research strategies based on natural products. For readers wishing to consider only the discovery of antimycobacterial natural products, we recommend the following review articles [22][23][24].…”

mentioning

confidence: 99%

Target Discovery Focused Approaches to Overcome Bottlenecks in the Exploitation of Antimycobacterial Natural Products

et al. 2018

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Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target prede ned pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to de ne the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products. Natural products: moving back to the forefront of antimycobacterial target discovery Tuberculosis (TB) is the world's leading cause of death from infectious disease, causing an estimated 1.4 million deaths in 2015 [1]. This effectively represents a reverse of trends seen during the middle years of the 20th century when antibiotics, developed from the 1940s, appeared to be effective in controlling the disease. However, over the last two decades TB is again a major public health hazard with the appearance of drug-resistant strains of TB, multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and more recently strains resistant to all the antitubercular chemotherapies [2]. This situation has arisen for a great extent due to the complex drug therapy regime used for TB which reduces patient compliance and adherence to prescribed medication. Thus, antitubercular chemotherapy comprises at least a 6-month drug regimen involving an initial 2-month phase of four agents (isoniazid, rifampicin, pyrazinamide and ethambutol) followed by an additional 4 months with isoniazid and rifampicin [3,4].MDR-TB is resistant to both ifampicin and isoniazid, the most effective antituberculous drugs. XDR-TB strains are resistant to at least rifampicin and isoniazid but also fluoroquinolones and to, at least, one of the injectable drugs; capreomycin, kanamycin or amikacin. Treatment of MDR-TB consists of a 2-year therapy with a combination of four to six first-and second-line antitubercular drugs [5]. TB control is therefore contingent on the development of new drugs and in the past decade there have been major efforts made in this area. There is also a need for new drugs that act quickly, giving fewer opportunities for the TB-causing organism to develop resistance. Any new drugs also need to be inexpensive to produce, so that it can be widely adopted in countries outside of the first world. Due to renewed research and development efforts, bedaquiline, a diarylquinolone, became the first anti-TB drug approved by the US FDA in more than 40 years [6]. Additionally, innovative methodologies have allowed the development of more effective therapies, the 'revitalization' of old drugs, re-use of drugs in different contexts, and the reduction of drugs rejected due to...

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“…5,6 Devido a estes fatores, a exploração de produtos naturais pela busca do desenvolvimento de novos quimioterápicos, mais específicos e eficientes, continua sendo prioridade de investigação de diversos pesquisadores. [7][8][9][10] O eugenol (1) (Figura 2) é um composto natural encontrado em várias plantas aromáticas como noz moscada, canela, folha de louro, sassafrás, mirra e manjericão.11 No entanto, o cravo da índia Eugenia caryophyllata (=Syzygium aromaticum) pode ser considerado a principal fonte natural do eugenol (1), pois representa entre 45% e 90% da composição do óleo essencial derivado desta espécie.Várias atividades biológicas foram relatadas para o eugenol (1), dentre elas destacam-se as atividades antibacteriana, antifúngica, antiplasmodial, antiviral, anti-inflamatória, analgésica, antioxidante, antidiabetes e citotóxica contra diferentes linhagens celulares de câncer.12,13 Uma investigação realizada sobre o efeito da atividade antiproliferativa do eugenol (1) contra as linhagens de células leucêmicas U-937, HL-60, HepG2, 3LL Lewis e SNU-C5, resultaram em valores de IC 50 iguais a 39,4, 23,7, 118,6, 89,6 e 129,4 µmol L -1 , …”

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Síntese E Avaliação Da Atividade Citotóxica De Derivados Do Eugenol Contendo Núcleos 1,2,3-Triazólicos

et al. 2018

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SYNTHESIS AND CYTOTOXIC ACTIVITY OF 1,2,3-TRIAZOLE DERIVATIVES OF EUGENOL. Eugenol is an aromatic compound found in several plant species. It presents important biological activities including cytotoxicity. In this paper, it is described the synthesis and the evaluation of the cytotoxic activity of eugenol derivatives bearing 1,2,3-triazole functionalities. Eugenol, extracted via hydrodistillation from dried flower buds of Eugenia caryophyllata (=Syzygium aromaticum), was submitted to alkylation reactions to afford two terminal alkynes in good yields. The key reaction involved in the preparation of eugenol derivatives corresponded to the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC), between alkynylated eugenol derivatives and different benzyl azides. The evaluation of the cytotoxicity of twenty seven synthesized derivatives against HL60 leukemia cell line revealed that at 100 µmol L -1 , five of them, namely 4-((4-allyl-2-methoxyphenoxy)methyl)-1-(3-bromobenzyl)-1H-1,2,3-triazole (6n), 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-benzyl-1H-1,2,3-triazole (7a), 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-chlorobenzyl)-1H-1,2,3-triazole (7c), 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-iodobenzyl)-1H-1,2,3-triazole (7e) and 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(3-bromobenzyl)-1H-1,2,3-triazole (7m), were capable of significantly decreasing cell viability. These most active triazolic derivatives were also evaluated against B16F10 melanoma and Nalm6 leukemia cell lines. While only compound 7a was active against the former, compounds 6n, 7a, and 7m displayed activity against the latter. Derivative 7a was active against all cell lines. It is believed that eugenol derivatives bearing triazole functionalities may represent a scaffold to be explored toward the development of new agents against cancer.Keywords: eugenol; triazole; cytotoxic activity; click chemistry; CuAAC reaction. INTRODUÇÃOO câncer correspondeu a uma das principais causas de mortes no século XX e vem difundindo-se de forma contínua e aumentando sua incidência no século XXI.1 Sua denominação está associada a um conjunto de mais de 100 doenças que têm em comum o crescimento desordenado (maligno) de células anormais que invadem os tecidos e órgãos, podendo espalhar-se (metástase) para outras regiões do corpo. Devido à rápida divisão celular, estas células podem se tornar muito agressivas e incontroláveis, determinando assim a formação de tumores ou neoplasias malignas.De acordo com a Organização Mundial da Saúde (OMS), o câncer é um problema de saúde pública, principalmente em países em desenvolvimento. A estimativa para o ano de 2025 aponta para a ocorrência de aproximadamente 20 milhões de novos casos. Investigações científicas multidisciplinares têm sido conduzidas buscando encontrar alternativas para combater esta doença, no entanto, a cura ainda não foi alcançada. Os principais tipos de tratamento empregados para o câncer baseiam-se, de forma geral, na associação da ressecção cirúrgica dos tumores ao tratamento radioterápico e a quimioterapi...

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The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

Cited by 178 publications

References 233 publications

New Antiparasitic Bis‐Naphthoquinone Derivatives

New Antiparasitic Bis‐Naphthoquinone Derivatives

Target Discovery Focused Approaches to Overcome Bottlenecks in the Exploitation of Antimycobacterial Natural Products

Síntese E Avaliação Da Atividade Citotóxica De Derivados Do Eugenol Contendo Núcleos 1,2,3-Triazólicos

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