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      Marine Alkaloids: Compounds with In Vivo Activity and Chemical Synthesis

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          Abstract

          Marine alkaloids comprise a class of compounds with several nitrogenated structures that can be explored as potential natural bioactive compounds. The scientific interest in these compounds has been increasing in the last decades, and many studies have been published elucidating their chemical structure and biological effects in vitro. Following this trend, the number of in vivo studies reporting the health-related properties of marine alkaloids has been increasing and providing more information about the effects in complex organisms. Experiments with animals, especially mice and zebrafish, are revealing the potential health benefits against cancer development, cardiovascular diseases, seizures, Alzheimer’s disease, mental health disorders, inflammatory diseases, osteoporosis, cystic fibrosis, oxidative stress, human parasites, and microbial infections in vivo. Although major efforts are still necessary to increase the knowledge, especially about the translation value of the information obtained from in vivo experiments to clinical trials, marine alkaloids are promising candidates for further experiments in drug development.

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          Clinical development success rates for investigational drugs.

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            Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

            The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review discusses plant-based natural product drug discovery and how innovative technologies play a role in next-generation drug discovery.
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              Lost in translation: animal models and clinical trials in cancer treatment.

              Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore the safety and efficacy identified in animal studies is generally not translated to human trials. Animal models can serve as an important source of in vivo information, but alternative translational approaches have emerged that may eventually replace the link between in vitro studies and clinical applications. This review summarizes the current state of animal model translation to clinical practice, and offers some explanations for the general lack of success in this process. In addition, some alternative strategies to the classic in vivo approach are discussed.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                28 June 2021
                July 2021
                : 19
                : 7
                : 374
                Affiliations
                [1 ]Centro Tecnológico de la Carne de Galicia, Parque Tecnológico de Galicia, rúa Galicia No. 4, San Cibrao das Viñas, 32900 Ourense, Spain; paulosichetti@ 123456ceteca.net (P.E.S.M.); mirianpateiro@ 123456ceteca.net (M.P.); rubendominguez@ 123456ceteca.net (R.D.)
                [2 ]Centro de Tecnologia, Programa de Pós-Graduação em Ciência de Alimentos, Instituto de Química, Universidade Federal do Rio de Janeiro, Avenida Athos da Silveira Ramos 149, Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil; carlosconte@ 123456id.uff.br
                [3 ]Jiangsu Key Laboratory of Crop Genetics and Physiology, College of Agriculture, Yangzhou University, Yangzhou 225009, China; 007298@ 123456yzu.edu.cn
                [4 ]Department of Food Science and Engineering, College of Ocean, Zhejiang University of Technology, Hangzhou 310014, China; Noman.rai66@ 123456gmail.com
                [5 ]Complejo Hospitalario Universitario de Ourense, 32005 Ourense, Spain; elena.movilla.fierro@ 123456sergas.es
                [6 ]Área de Tecnología de los Alimentos, Facultad de Ciencias de Ourense, Universidad de Vigo, 32004 Ourense, Spain
                Author notes
                [* ]Correspondence: jmlorenzo@ 123456ceteca.net
                Author information
                https://orcid.org/0000-0002-9682-4594
                https://orcid.org/0000-0001-6133-5080
                https://orcid.org/0000-0002-2764-504X
                https://orcid.org/0000-0002-7725-9294
                Article
                marinedrugs-19-00374
                10.3390/md19070374
                8306672
                34203532
                28bf6c77-2a39-449f-9d53-e3eccb546cc0
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 28 May 2021
                : 24 June 2021
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                animal studies,marine alkaloids,biological activity,cancer,cardiovascular diseases,inflammation,chemical synthesis

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