The strategies and techniques of drug discovery from natural products

Zhang, Li; Song, Junke; Kong, Ling-Lei; Yuan, Tianyi; Wan, Lijuan; Zhang, Wen; Hou, Biyu; Lü, Yang; Du, Guanhua

doi:10.1016/j.pharmthera.2020.107686

Cited by 153 publications

(85 citation statements)

References 65 publications

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“…The high structural and physicochemical diversity of natural products makes them a valuable source to discover and develop new bioactive compounds with different pharmaceutical, cosmetic, biotechnological, agrochemical, and food applications (Rayan et al, 2017 ). Success histories of natural product-based drugs have been reported in the pharmaceutical industry and include pilocarpine, quinine, morphine, and artemisinin (Newman and Cragg, 2016 ; Zhang L. et al, 2020 ). Natural products represent relevant importance in the discovery and development of new bioinspired bioactive compounds, and more than 50% of the developed drugs approved by the United States Food and Drug Administration (USFDA, 1981–2019) are derived or bioinspired from compounds obtained from natural sources (Newman and Cragg, 2020 ).…”

Section: Natural Products As Sources Of Novel Bioactive Compounds and The Paradigms Of Their Explorationmentioning

confidence: 99%

“…The systematic search for natural sources to obtain valuable compounds to develop products with commercial value and industrial purposes remains the most challenging task in bioprospecting (Skirycz et al, 2016 ; Roumpeka et al, 2017 ; Cubillos et al, 2019 ). The traditional approach to discover new bioactive compounds from natural sources includes sequential steps that are obtained from the biological material using ethnological knowledge, extraction, fractionation/isolation, chemical characterization, and, finally, the execution of the biological assays of the isolated or fractionated natural products (Zhang L. et al, 2020 ). Subsequent analyses include the lead compound optimization using chemical synthesis to perform structural modifications in order to improve their pharmacodynamic and pharmacokinetic properties and to increase their biological activities (Huffman and Shenvi, 2019 ).…”

Section: Natural Products As Sources Of Novel Bioactive Compounds and The Paradigms Of Their Explorationmentioning

confidence: 99%

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Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

et al. 2021

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Natural products are continually explored in the development of new bioactive compounds with industrial applications, attracting the attention of scientific research efforts due to their pharmacophore-like structures, pharmacokinetic properties, and unique chemical space. The systematic search for natural sources to obtain valuable molecules to develop products with commercial value and industrial purposes remains the most challenging task in bioprospecting. Virtual screening strategies have innovated the discovery of novel bioactive molecules assessing in silico large compound libraries, favoring the analysis of their chemical space, pharmacodynamics, and their pharmacokinetic properties, thus leading to the reduction of financial efforts, infrastructure, and time involved in the process of discovering new chemical entities. Herein, we discuss the computational approaches and methods developed to explore the chemo-structural diversity of natural products, focusing on the main paradigms involved in the discovery and screening of bioactive compounds from natural sources, placing particular emphasis on artificial intelligence, cheminformatics methods, and big data analyses.

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Section: Natural Products As Sources Of Novel Bioactive Compounds and The Paradigms Of Their Explorationmentioning

confidence: 99%

Section: Natural Products As Sources Of Novel Bioactive Compounds and The Paradigms Of Their Explorationmentioning

confidence: 99%

Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

et al. 2021

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“…Natural products have been used in traditional medicine for a long time, and since the appearance of modern science, they have been recognized as valuable sources of new drugs [ 1 , 2 , 3 , 4 , 5 ]. Considerable money has been invested in their isolation from natural sources and characterization of their structures and biological activities.…”

Section: Introductionmentioning

confidence: 99%

Biocatalysis in the Chemistry of Lupane Triterpenoids

Bachořík

Urban

2021

Molecules

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Pentacyclic triterpenes are important representatives of natural products that exhibit a wide variety of biological activities. These activities suggest that these compounds may represent potential medicines for the treatment of cancer and viral, bacterial, or protozoal infections. Naturally occurring triterpenes usually have several drawbacks, such as limited activity and insufficient solubility and bioavailability; therefore, they need to be modified to obtain compounds suitable for drug development. Modifications can be achieved either by methods of standard organic synthesis or with the use of biocatalysts, such as enzymes or enzyme systems within living organisms. In most cases, these modifications result in the preparation of esters, amides, saponins, or sugar conjugates. Notably, while standard organic synthesis has been heavily used and developed, the use of the latter methodology has been rather limited, but it appears that biocatalysis has recently sparked considerably wider interest within the scientific community. Among triterpenes, derivatives of lupane play important roles. This review therefore summarizes the natural occurrence and sources of lupane triterpenoids, their biosynthesis, and semisynthetic methods that may be used for the production of betulinic acid from abundant and inexpensive betulin. Most importantly, this article compares chemical transformations of lupane triterpenoids with analogous reactions performed by biocatalysts and highlights a large space for the future development of biocatalysis in this field. The results of this study may serve as a summary of the current state of research and demonstrate the potential of the method in future applications.

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“…The alkaloid pilocarpine (5) can also be cited, obtained from leaves of Pilocarpus trees, Rutaceae (jaborandi), formerly used to treat glaucoma and currently employed to relieve xerostomia (Skirycz et al 2016). Another example is tubocurarine chloride or d-tubocurarine (6), a constituent of the curare, a traditional preparation made with Chondrodendron tomentosum Ruiz & Pav., Menispermaceae, introduced in anesthesiology in the 1940s due to its relaxing effect of skeletal musculature (Zhang et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Paving New Roads Towards Biodiversity-Based Drug Development in Brazil: Lessons from the Past and Future Perspectives

Braga

2021

Rev. Bras. Farmacogn.

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Although Brazil gathers two fundamental features to occupy a leading position on the development of biodiversity-based medicines, the largest flora on earth and a broad tradition on the use of medicinal plants, the number of products derived from the national genetic heritage is so far modest, either as single drugs or as herbal medicines. This article highlights some aspects that may have contributed to the low rates of success and proposes new insights for innovation. We initially approach the use of medicinal plants in Brazil, molded by its ethnic diversity, and the development of the local pharmaceutical industry. A discussion of some governmental initiatives to support plant-based drug development is then presented. Employing the economic concept of "middle-income trap," we further propose that Brazil is stuck in a "middle-level science trap," since the increase in the number of scientific publications that launched the country to an intermediate publishing position has not been translated into drug development. Two new approaches to escape from this trap are presented, which may result in innovative drug development. The first is based on the exploitation of the antifragility properties of herbal products aiming to investigate non-canonical pharmacodynamics mechanisms of action, aligned with the concepts of system biology. The second is the manufacture of herbal products based on the circular economy principles, including the use of byproducts for the development of new therapeutical agents. The adoption of these strategies may result in innovative phytomedicines, with global competitiveness.

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The strategies and techniques of drug discovery from natural products

Cited by 153 publications

References 65 publications

Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

Biocatalysis in the Chemistry of Lupane Triterpenoids

Paving New Roads Towards Biodiversity-Based Drug Development in Brazil: Lessons from the Past and Future Perspectives

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