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      A Comprehensive Review on Medicinal Plants as Antimicrobial Therapeutics: Potential Avenues of Biocompatible Drug Discovery

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          Abstract

          The war on multidrug resistance (MDR) has resulted in the greatest loss to the world’s economy. Antibiotics, the bedrock, and wonder drug of the 20th century have played a central role in treating infectious diseases. However, the inappropriate, irregular, and irrational uses of antibiotics have resulted in the emergence of antimicrobial resistance. This has resulted in an increased interest in medicinal plants since 30–50% of current pharmaceuticals and nutraceuticals are plant-derived. The question we address in this review is whether plants, which produce a rich diversity of secondary metabolites, may provide novel antibiotics to tackle MDR microbes and novel chemosensitizers to reclaim currently used antibiotics that have been rendered ineffective by the MDR microbes. Plants synthesize secondary metabolites and phytochemicals and have great potential to act as therapeutics. The main focus of this mini-review is to highlight the potential benefits of plant derived multiple compounds and the importance of phytochemicals for the development of biocompatible therapeutics. In addition, this review focuses on the diverse effects and efficacy of herbal compounds in controlling the development of MDR in microbes and hopes to inspire research into unexplored plants with a view to identify novel antibiotics for global health benefits.

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          Discovery and resupply of pharmacologically active plant-derived natural products: A review

          Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.
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            Antibiotics and Bacterial Resistance in the 21st Century

            Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed.
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              Counting on natural products for drug design.

              Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.
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                Author and article information

                Journal
                Metabolites
                Metabolites
                metabolites
                Metabolites
                MDPI
                2218-1989
                01 November 2019
                November 2019
                : 9
                : 11
                : 258
                Affiliations
                [1 ]Department of Molecular and Cellular Engineering (MCE), Jacob Institute of Biotechnology and Bioengineering (JIBB), Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj (Allahabad), Uttar Pradesh 211007, India
                [2 ]Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Av. Vasco de Quiroga 15. Col. Belisario Domínguez Sección XVI. C.P. Tlalpan, Ciudad de México 14080, Mexico; nadia.jacobo@ 123456gmail.com
                [3 ]Department of Food Science, College of Agriculture, University of Basrah, Basrah 61004, Iraq
                [4 ]Department of Plant, Soil and Agricultural Systems, Southern Illinois University, Carbondale, IL 62901, USA; naoufal.lakhssassi@ 123456siu.edu
                Author notes
                [* ]Correspondence: ushuats@ 123456gmail.com (U.A.); ammaragr@ 123456siu.edu (A.A.)
                Author information
                https://orcid.org/0000-0001-5924-7866
                https://orcid.org/0000-0001-7750-5988
                Article
                metabolites-09-00258
                10.3390/metabo9110258
                6918160
                31683833
                4ea7c2d5-fa06-4834-9dfa-5b5d5d37c4a0
                © 2019 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 September 2019
                : 28 October 2019
                Categories
                Review

                antibiotics,infectious disease,antimicrobial resistant,secondary metabolites,immune response

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