Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections

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Abstract

Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants. In this review, we have collected data obtained from various research groups on the antimicrobial activities of these alkaloids against conventional antibiotic-resistant strains. In addition, the structure–function relationship was described and commented on, highlighting the high potential of alkaloids as antimicrobials.

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Antimicrobial activity of flavonoids

T.P. Tim Cushnie, Andrew Lamb (2005)

Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (−)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2′-trihydroxy-5′-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

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

Atanas Atanasov, Birgit Waltenberger, Eva-Maria Pferschy-Wenzig … (2015)

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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Antimicrobial peptides: Application informed by evolution

Brian Lazzaro, Michael Zasloff, Jens Rolff (2020)

Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.

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Derek J. McPhee: Role: Academic Editor

Journal

Journal ID (nlm-ta): Molecules

Journal ID (iso-abbrev): Molecules

Journal ID (publisher-id): molecules

Title: Molecules

Publisher: MDPI

ISSN (Electronic): 1420-3049

Publication date (Electronic): 09 August 2020

Publication date Collection: August 2020

Volume: 25

Issue: 16

Electronic Location Identifier: 3619

Affiliations

[1 ]Center For Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy; bruno.casciaro@ 123456iit.it (B.C.); laura.mangiardi@ 123456uniroma1.it (L.M.); Isabella.romeo@ 123456uniroma1.it (I.R.)

[2 ]Department of Chemistry and Technology of Drugs, “Department of Excellence 2018−2022”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; antonia.iazzetti@ 123456uniroma1.it (A.I.); andrea.calcaterra@ 123456uniroma1.it (A.C.); antonella.goggiamani@ 123456uniroma1.it (A.G.); deborah.quaglio@ 123456uniroma1.it (D.Q.)

[3 ]Laboratory affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; floriana.cappiello@ 123456uniroma1.it (F.C.); mariarosa.loffredo@ 123456uniroma1.it (M.R.L.)

Author notes

[* ]Correspondence: francesca.ghirga@ 123456iit.it (F.G.); marialuisa.mangoni@ 123456uniroma1.it (M.L.M.); bruno.botta@ 123456uniroma1.it (B.B.)

Author information

Bruno Casciaro https://orcid.org/0000-0003-1295-1084

Laura Mangiardi https://orcid.org/0000-0002-9937-4365

Andrea Calcaterra https://orcid.org/0000-0001-7036-6620

Maria Luisa Mangoni https://orcid.org/0000-0002-5991-5868

Bruno Botta https://orcid.org/0000-0001-8707-4333

Article

Publisher ID: molecules-25-03619

DOI: 10.3390/molecules25163619

PMC ID: 7466045

PubMed ID: 32784887

SO-VID: e1dc3935-af1c-4a2d-b254-02b8d5530f45

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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/).

Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections

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Microbiology Independent Research Journal (MIR Journal)

Most cited references 127

Antimicrobial activity of flavonoids

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

Antimicrobial peptides: Application informed by evolution

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