Productos naturales en la búsqueda de compuestos antimicrobianos :
estrategias actuales
Keywords:
Productos naturales, actividad antimicrobiana, resistencia a fármacos, semisíntesis, vehiculizaciónAbstract
Antimicrobial resistance is one of the most serious health problems worldwide, as many pathogens are rapidly developing resistance to the existing treatments. In the current scenario, there is no effective therapeutic agent with the potential to reverse antimicrobial resistance, so many leading laboratories (at industrial and academic level) are working intensively to discover new therapeutic agents. In this sense, natural compounds of plant origin are relatively less studied in the context of antimicrobial drug development.
Natural products have been of great interest in the drug discovery process due to their structural diversity and complexity, chemical novelty, and bioactivity. Thus, to date, the isolation of natural compounds from various organisms has been described, including bacteria, fungi, invertebrates, marine organism and plants. All of these have made significant contributions to the development of drugs for various human diseases. To cite some examples, doxorubicin, bleomycins, penicillins, epothilones, paclitaxel, camptothecin, podophyllotoxins and vinca alkaloids are today some of the best-known active ingredients derived from bacteria, fungi or plants. For all above, in this perspective article, we will address the topic from the different approaches that are currently used to explore the antimicrobial therapeutic potential of metabolites of plant origin or their derivatives.
Finally, after analyzing the sections presented, we arrive to the conclusion of the urgent need for exhaustive research into the antimicrobial potential of plant metabolites. Indeed, these privileged biologically relevant structures can constitute new chemical entities with improved antimicrobial efficacy through their derivatization or vehiculization. Another important point to highlight is the need to examine the role of these compounds together with antibiotics currently used in clinical practice in order
to explore possible synergistic effects.
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References
CroftsT.S., GasparriniA.J., DantasG. Next-generation approachestounderstand and combattheantibioticresistome. Nat. Rev. Microbiol.(2017)
: 422-434.
Chis A.A., Rus L.L., Morgovan C., Arseniu A.M., Frum A., Vonica-Tincu A.L., y col. Microbial Resistance to Antibiotics and Effective Antibiotherapy.
Biomedicines.(2022) 10(1121): 1-38.
Zhen X, Lundborg CS, Sun X, Hu X, Dong H. Economic burden of antibiotic resistance in ESKAPE organisms: A systematic review. Antimicrob.
Resist. Infect. Control.(2019) 8(137): 1-23.
O’Neill, J. TheReviewon AntimicrobialResistance, AntimicrobialResistance: Tacklingacrisisforthehealth and wealthofnations.(2015) 1-22.
MinisteriodeSaludArgentino. NuevaLeydePrevenciónyControldelaResistenciaAntimicrobiana, 10deagostode2022. https://www.argentina.
gob.ar/noticias/nueva-ley-de-prevencion-y-control-de-la-resistencia-antimicrobiana, últimoacceso29/9/2023.
Durand G.A., RaoultD., DubourgG. Antibioticdiscovery: history, methodsand perspectives. Int. J. Antimicrob. Agents.(2019) 53: 371-382.
Antibioticresistancethreatsin theUnited States, 2019Atlanta, Georgia. https://stacks.cdc.gov/view/cdc/82532
Annunziato G. Strategies to Overcome Antimicrobial Resistance (AMR) Making Use of Non-Essential Target Inhibitors: A Review. Int. J. Mol. Sci.
(2019) 20(5844): 1-25.
RossiterS.E., FletcherM.H., WuestW.M. NaturalProductsasPlatformstoOvercomeAntibioticResistance. Chem. Rev.(2017) 117: 12415-12474.
Jadimurthy R., Jagadish S., Nayak S.C., Kumar S., Mohan C.D., Rangappa K.S. Phytochemicals as Invaluable Sources of Potent Antimicrobial
AgentstoCombatAntibioticResistance., Life(2023) 13(948): 1-34.
DiasD.A., UrbanS., RoessnerU. AHistoricaloverviewofnaturalproductsin drugdiscovery. Metabolites.(2012) 2: 303-336.
Toledo C., Kutschker A. Plantas Medicinales en el Parque nacional los alerces, Chubut, Patagonia argentina. Bol. Soc.
Argent. Bot.(2012) 47: 461-470.
Estomba D., Ladio A., Lozada M. Medicinal wild plant knowledge and gathering patterns in a Mapuche community
fromNorth-westernPatagonia. J. Ethnopharmacol.(2006) 103: 109-119.
FarmacopeaArgentina, 2013,7maedición, AdministraciónNacionaldeMedicamentos, AlimentosyTecnologíaMédica,
CiudadAutónomadeBuenosAires, Argentina: MinisteriodeSalud delaNación.
Yagüe E., Sun H., Hu Y. East Wind, West Wind: Toward the modernization of traditional Chinese medicine. Front. Neurosci.(
16(1057817): 1-17.
LiG., Lou H.X. Strategiestodiversifynaturalproductsfordrugdiscovery. Med. Res. Rev.(2018) 38: 1255-1294.
Newman D.J., Cragg G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to
/2019. J. Nat. Prod.(2020) 83: 770-803.
Van Der Kooy F., Sullivan S.E. The complexity of medicinal plants: The traditional Artemisia annua formulation, current
statusandfutureperspectives. J. Ethnopharmacol.(2013) 150: 1-13.
Majhi S., Das D. Chemical derivatization of natural products: Semisynthesis and pharmacological aspects- A decade update.
Tetrahedron.(2021) 78(131801): 1-22.
Evans B.E., Rittle K.E., Bock M.G., Dipardo R.M., Freidinger R.M., Whitter W.L., y col. Articles Methods for Drug Discovery: Development of Potent,
Selective, OrallyEffectiveCholecystokinin Antagonistst. J. Med. Chem.(1988) 31: 2235-2246.
Lovering F., Bikker J., Humblet C. Escape from flatland: Increasing saturation as an approach to improving clinical success. J. Med. Chem. (2009)
: 6752-6756.
Camp D., GaravelasA., CampitelliM. AnalysisofPhysicochemicalPropertiesforDrugsofNaturalOrigin. J NatProd.(2015) 78(6):1370-1382.
Subramanian A.P., Jaganathan S.K., Manikandan A., Pandiaraj K.N., Gomathi N., Supriyanto E. Recent trends in nano-based drug delivery systemsforefficientdeliveryofphytochemicalsinchemotherapy.
RSCAdv.(2016) 6: 48294-48314.
Cadoná F.C., Machado A.K., Bodenstein D., Rossoni C., Favarin F.R., Ourique A.F., editores. Natural product–based nanomedicine: Polymeric
nanoparticlesasdeliverycargoesoffoodbioactivesand nutraceuticalsforanticancerpurposes. En: AdvancesandAvenuesintheDevelopmentof
NovelCarriersforBioactivesandBiologicalAgents. Elsevier; 2020, p. 37–67.
Brown D.G., BoströmJ. WhereDoRecentSmallMoleculeClinicalDevelopmentCandidatesComeFrom? J. Med. Chem.(2018) 61(21): 9442-
HillR.A., Sutherland A. Hotoffthepress. Nat. Prod. Rep.(2014) 31: 1671-1675.
GrivasP.D., KiarisH., Papavassiliou A.G. Tacklingtranscriptionfactors: Challengesin antitumortherapy. TrendsMol. Med.(2011) 17: 537-538.
AsakawaY., LudwiczukA. ChemicalConstituentsofBryophytes: Structuresand BiologicalActivity. J. Nat. Prod.(2018) 81: 641-660.
RíosJ.L., RecioM.C. Medicinalplantsandantimicrobialactivity. J. Ethnopharmacol.(2005) 100: 80-84.
Gertsch J. Botanicaldrugs, synergy, and networkpharmacology: Forth and backtointelligentmixtures. PlantaMed.(2011) 77: 1086-1098.
CaesarL.K., Cech N.B. Synergyand antagonisminnaturalproductextracts: When 1+ 1doesnotequal2. Nat. Prod. Rep.(2019) 36: 869-888.
Doern C.D. Whendoes2plus2equal5? Areviewofantimicrobialsynergytesting. J. Clin. Microbiol.(2014) 52: 4124-4128.
Dal Piaz F., Bader A., Malafronte N., D’Ambola M., Petrone A.M., Porta A., y col. Phytochemistry of compounds isolated from the leaf-surface
extractofPsiadiapunctulata(DC.) Vatkegrowingin SaudiArabia. Phytochem.(2018) 155: 191-202.
Donadio G., Chini M.G., Parisi V., Mensitieri F., Malafronte N., Bifulco G., y col. Diterpenoid Constituents of Psiadia punctulata and Evaluation of
TheirAntimicrobialActivity. J. Nat. Prod.(2022) 85(7):1667-1680.
Besbes Hlila M., Mosbah H., Majouli K., Ben Nejma A., Ben Jannet H., Mastouri M., y col. Antimicrobial Activity of Scabiosa arenaria Forssk.
ExtractsandPureCompoundsUsingBioguided Fractionation. ChemBiodivers.(2016) 1: 1262-1272.
CastroI., FabreN., Bourgeade-DelmasS., SaffonN., GandiniC., Sauvain M., ycol. StructuralCharacterization andAnti-infectiveActivityof9,10-Seco-
-norcycloartaneGlycosidesIsolated fromtheFlowersofthePeruvianMedicinalPlantCordialutea. J. Nat. Prod.(2019) 82(12): 3233-3341.
El-ShiekhR.A., Hassan M., HashemR.A., Abdel-SattarE. Bioguidedisolation ofantibiofilmand antibacterialpregnaneglycosidesfromcaralluma
quadrangula: Disarmingmultidrug-resistantpathogens. Antibiotics.(2021) 10(7): 1-11.
Ramallo, I.A., Salazar, M.O., Furlan, R.L. EnzymaticBioautographicMethods. En: TargetingEnzymesforPharmaceuticalDevelopment. Methods
in MolecularBiology. Labrou, N. Editor. NuevaYork(EstadosUnidos): EditorialHumana, 2020, vol2089, p. 179-189.
ChomaI.M., GrzelakE.M. Bioautographydetection inthin-layerchromatography. J. Chromatogr. A.(2011) 1218: 2684-2691.
Morel A.F, Araujo C.A., Da Silva U.F., Hoelzel S.C., Zachiazachia R., Bastos N.R. Antibacterial cyclopeptide alkaloids from the bark of Condalia buxifolia.
Phytochem.(2002) 61: 561-566.
TatsutaK. Totalsynthesisofthebigfourantibioticsand related antibiotics. J. Antibiot.(2013) 66: 107-129.
Tatsuta,K., Yoshimoto, T., Gunji, H.; Okado, Y., Takahashi, M. TheFirstTotalSynthesisofNatural (-)-Tetracycline. Chem. Lett.(2000) 29: 646-647.
Van Der Hooft J.J., Mohimani H., Bauermeister A., Dorrestein P.C., Duncan K.R., Medema M.H. Linking genomics and metabolomics to chart
specializedmetabolicdiversity. Chem. Soc. Rev.(2020) 49: 3297-3314.
Miethke M., Pieroni M., Weber T., Brönstrup M., Hammann P., Halby L., y col. Towards the sustainable discovery and development of new
antibiotics. Nat. Rev. Chem.(2021) 5: 726-749.
Lukežic T., Lešnik U., Podgoršek A., Horvat J., Polak T., Šala, M., y col. Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis
sulphurea: aplatformforproducingnoveltetracyclineantibiotics. Microbiology(2013) 159: 2524-2532.
Grandclaudon C., BirudukotaN.V.S., ElgaherW.A.M., JumdeR.P., YahiaouiS., ArisettiN., ycol. Semisynthesisandbiological
evaluation ofamidochelocardinderivativesasbroad-spectrumantibiotics. Eur. J. Med. Chem.(2020) 188(112005): 1-11.
GallowayW.R., Isidro-LlobetA., SpringD.R. Diversity-oriented synthesisasatoolforthediscoveryofnovelbiologicallyactivesmallmolecules.
Nat. Comm.(2010) 1: 1-13.
BurkeM.D., SchreiberS.L. APlanningStrategyforDiversity-OrientedSynthesis. Angew. Chem. Int. Ed.(2004) 43: 46-58.
Kong, Y., Li, L., Zhao, L., Yu, P., Li, D. A patent review of berberine and its derivatives with various pharmacological activities
(2016–2020). ExpertOpinion onTherapeuticPatents.(2022) 32(2): 211-223.
Zhang Y., Gu Y., Ren H., Wang S., Zhong H., Zhao X., y col. Gut microbiome-related effects of berberine and probiotics on
type2diabetes(thePREMOTEstudy). Nat. Commun.(2020) 11(1): 1-12.
Chiou W.F., YenM.H., ChenC.F. Mechanismofvasodilatoryeffectofberberineinratmesentericartery. Eur. J. Pharmacol.
(1991) 201: 35-40.
Sun H., AnsariM.F., BattiniN., BheemanaboinaR.R.Y., Zhou C.H. NovelpotentialartificialMRSADNAintercalators: Synthesisand
biologicalevaluationofberberine-derived thiazolidinediones. Org. Chem. Front.(2019) 6(3): 319-334.
Gao W.W., Gopala L., Bheemanaboina R.R.Y., Zhang G.B., Li S., Zhou C.H. Discovery of 2-aminothiazolyl berberine derivativesaseffectivelyantibacterialagentstoward
clinicallydrug-resistantGram-negativeAcinetobacterbaumanii. Eur. J. Med. Chem.
(2018) 146: 15-37.
Olleik H., Yacoub T., Hoffer L., Gnansounou S.M., Benhaiem‐Henry K., Nicoletti C., y col. Synthesis and evaluation of the antibacterial activities of
‐substituted berberinederivatives. Antibiotics.(2020) 9(7): 1-31.
DemekhinO.D., ZagrebaevA.D., BurovO.N., KletskiiM.E., PavlovichN.V., BereznyakE.A., ycol. Thefirst13-vinylderivativesofberberine: synthesis
andantimicrobialactivity. Chem. Heterocycl. Compd.(2019) 55(11):1128-1130.
WangJ., YangT., ChenH., Xu Y.N., Yu L.F., Liu T., ycol. Thesynthesisand antistaphylococcalactivityof9,13-disubstituted berberinederivatives. Eur.
J. Med. Chem.(2017) 127: 424-433.
Chen L., Zhu L., Chen J., Chen W., Qian X., Yang Q. Crystal structure-guided design of berberine-based novel chitinase inhibitors. J. Enzyme Inhib.
Med. Chem.(2020) 35(1):1937-1943.
Ling Y., Wu L.L., Qian L.I., Hu Q.M., Zhang S.Y., Kang L., y col. Novel berberine derivatives: Design, synthesis, antimicrobial effects, and molecular
dockingstudies. Chin. J. Nat. Med.(2018) 16: 774-781.
Jeyakkumar P., Zhang L., Avula S.R., Zhou C.H. Design, synthesis and biological evaluation of berberine-benzimidazole hybrids as new type of
potentiallyDNA-targetingantimicrobialagents. Eur. J. Med. Chem.(2016) 122: 205-215.
Jia D., Dou Y., Li Z., Zhou X., Gao Y., Chen K., y col. Design, synthesis and evaluation of a baicalin and berberine hybrid compound as therapeutic
agentforulcerativecolitis. Bioorg. Med. Chem.(2020) 28(20): 115697.
Khan S., Hussain A., Attar F., Bloukh S.H., Edis Z., Sharifi M., y col. A review of the berberine natural polysaccharide nanostructures as potential
anticancerand antibacterialagents. BiomedicineandPharmacotherapy.(2022) 146: 112531.
QianC.-D., WuX.-C., TengY., ZhaoW.-P., LiO., FangS.- G., HuangZ.-H., GaoH.-C. Battacin(OctapeptinB5), aNewCyclicLipopeptideAntibioticfromPaenibacillusTianmuensisActiveagainstMultidrug-
ResistantGram-NegativeBacteria. Antimicrob. AgentsChemother.(2012) 56: 1458-1465.
Kihara S., De Zoysa G. H., Shahlori R., Vadakkedath P. G., Ryan T. M., Mata, J. P., Sarojini, V., McGillivray, D. J. Solution Structure of Linear Battacin
Lipopeptides − the Effect of Lengthening Fatty Acid Chain. Soft Matter. (2019) 15: 7501-7508.
YimV., KavianiniaI., KnottenbeltM. K., FergusonS. A., CookG. M., SwiftS., ChakrabortyA., Allison J. R., Cameron A. J., HarrisP. W. R., BrimbleM. A.
“CLipP”ingonLipidstoGenerateAntibacterialLipopeptides. Chem. Sci.(2020) 11: 5759-5765.
Méndez L., SalazarM.O., RamalloA.I, Furlan R.L. Brominated extractsassourceofbioactivecompounds. ACSComb Sci.(2011) 13(2): 200-204.
López S.N., RamalloA.I., GonzalezSierraM., ZacchinoS.A., Furlan R.L. Chemicallyengineered extractsasan alternativesourceofbioactivenatural
product-likecompounds. PNAS(2006) 104(2): 441-444.
Ramallo A.I., Salazar M.O., García P., Furlan R.L. Chemical Diversification of Natural Product Extracts. En: Studies in Natural Products Chemistry.
Atta-ur-Rahman F.R.S, editor. Ámsterdam,(PaísesBajos): EditorialElsevierB.V.; 2019, vol60, p. 371-398.
Hoffman P.S. Antibacterialdiscovery: 21stcenturychallenges. Antibiotics.(2020) 9(5): 1-10.
RiceL.B. Federalfundingforthestudyofantimicrobialresistancein nosocomialpathogens: NoESKAPE. J. Infect. Dis.(2008) 197: 1079-1081.
ZhaoS., AdamiakJ.W., BonifayV., MehlaJ., ZgurskayaH.I., Tan D.S. Definingnewchemicalspacefordrugpenetration intoGram-negativebacteria.
Nat. Chem. Biol.(2020) 16(12): 1293-1302.
Du D., Wang-Kan X., NeubergerA., vanVeen H.W., PosK.M., PiddockL.J.V., ycol. Multidrugeffluxpumps: structure, function andregulation. Nat.
Rev. Microbiol.(2018) 16: 523-539.
AndrewsL.D., KaneT.R., DozzoP., HaglundC.M., HilderbrandtD.J., LinsellM.S., ycol. Optimization and MechanisticCharacterizationofPyridopyrimidineInhibitorsofBacterialBiotin
Carboxylase. J Med. Chem.(2019) 62(16):7489-7505.
RichterM.F., Drown B.S., RileyA.P., GarciaA., ShiraiT., SvecR.L., ycol. Predictivecompoundaccumulation rulesyield abroad-spectrumantibiotic.
Nature(2017) 545(7654):299-304.
Muñoz K.A., Hergenrother P.J. Facilitating Compound Entry as a Means to Discover Antibiotics for Gram-Negative Bacteria. Acc. Chem. Res.
(2021) 54(6): 1322-1333.
MorrisonK.C., HergenrotherP.J. Natural productsasstarting pointsforthesynthesisofcomplexand diversecompounds. Nat. Prod. Rep.(2014)
(1): 6-14.
Motika S.E., Hergenrother P.J. Re-engineering natural products to engage new biological targets. Nat. Prod. Rep. (2020)
(11): 1395-1403.
Richter M.F., Hergenrother P.J. The challenge of converting gram-positive-only compounds into broad-spectrum antibiotics.
Ann. N. Y. Acad. Sci.(2019) 1435: 18-38.
Parkinson E.I., Bair J.S., Nakamura B.A., Lee H.Y., Kuttab H.I., Southgate E.H., y col. Deoxynybomycins inhibit mutant DNA
gyraseand rescuemiceinfectedwith fluoroquinolone-resistantbacteria. Nat. Commun.(2015) 22,6: 6947.
ParkerE.N., Drown B.S., GeddesE.J., LeeH.Y., IsmailN., LauG.W., ycol. Implementation ofpermeationrulesleadstoaFabI
inhibitorwith activityagainstGram-negativepathogens. NatureMicrobiology(2020) 5: 67-75.
Parker E.N., Cain B.N., Hajian B., Ulrich R.J., Geddes E.J., Barkho S., y col. An Iterative Approach Guides Discovery of the
FabIInhibitorFabimycin, aLate-StageAntibioticCandidatewith In VivoEfficacyagainstDrug-ResistantGram-NegativeInfections.
ACSCent. Sci.(2022) 8(8): 1145-1158.
Motika S.E., Ulrich R.J., Geddes E.J., Lee H.Y., Lau G.W., Hergenrother P.J. Gram-Negative Antibiotic Active through Inhibitionofan
EssentialRiboswitch. J. Am. Chem. Soc.(2020) 142(24):10856-10862.
Perlmutter S.J., Geddes E.J., Drown B.S., Motika S.E., Lee M.R., Hergenrother P.J. Compound Uptake into E. coli Can Be
Facilitated byN-AlkylGuanidiniumsand Pyridiniums. ACSInfect. Dis.(2021) 7(1):162-173.
Zhang C., Yan L., Wang X., Zhu S., Chen C., Gu Z., y col. Progress, challenges, and future of nanomedicine. Nano Today.
(2020) 35: 101008.
MinY., CasterJ.M., Eblan M.J., WangA.Z. ClinicalTranslationofNanomedicine. Chem. Rev.(2015) 115: 11147-11190.
LiZ., ZhaoT., LiJ., Yu Q., FengY., XieY., ycol. NanomedicineBased onNaturalProducts: ImprovingClinicalApplication Potential. J. Nanomat.(2022)
: 3066613.
ChamundeeswariM., JeslinJ., VermaM.L. Nanocarriersfordrugdeliveryapplications. Environ. Chem. Lett.(2019) 17: 849-865.
Mansuri A., Chaudhari R., Nasra S., Meghani N., Ranjan S., Kumar A. Development of food-grade antimicrobials of fenugreek oil nanoemulsion— bioactivityand toxicityanalysis. Environ. Sci. Pollut. Res.(2023) 30(10): 24907-24918.
Cui R., Jiang K., Yuan M., Cao J., Lin L., Tang Z., y col. Antimicrobial film based on polylactic acid and carbon nanotube for controlled cinnamaldehyderelease.
J. Mater. Res. Technol.(2020) 9(5):10130-10138.
Rodenak-Kladniew B., Scioli Montoto S., Sbaraglini M.L., Di Ianni M., Ruiz M.E., Talevi A., y col. Hybrid Ofloxacin/eugenol co-loaded solid lipid
nanoparticleswithenhancedand targetableantimicrobialproperties. Int. J. Pharm.(2019) 569: 118575.
Zhang Y., Cheng X., Zhang Y., Xue X., Fu Y. Biosynthesis of silver nanoparticles at room temperature using aqueous aloe leaf extract and antibacterialproperties.
ColloidsSurf. APhysicochem. Eng. Asp.(2013) 423: 63-68.
Sabino C. P., Wainwright M., Ribeiro M. S., Sellera F. P., Dos Anjos C., da Silva Baptista, M., Lincopan, N. Global priority multidrug-resistant pathogensdonotresistphotodynamictherapy.
J. Photochem. Photobiol. B, Biol.(2020) 208: 111893
Kwiatkowski S., Knap B., Przystupski D., Saczko J., Kdzierska E., Knap-Czop K., y col. Photodynamic therapy – mechanisms, photosensitizers and
combinations. Biomed. Pharmacother.(2018) 106: 1098-1107.
WarrierA., MazumderN., PrabhuS., SatyamoorthyK., MuraliT.S. Photodynamictherapytocontrolmicrobialbiofilms. PhotodiagnosisPhotodyn.
Ther.(2021) 33: 102090.
Hochma E., Yarmolinsky L., Khalfin B., Nisnevitch M., Ben-Shabat S., Nakonechny F. Antimicrobial Effect of Phytochemicals from Edible Plants.
Processes.(2021) 9: 2089.
RoyR., TiwariM., DonelliG., TiwariV. Strategiesforcombatingbacterialbiofilms: Afocuson anti-biofilmagentsand theirmechanismsofaction.
Virulence.(2018) 9: 522-554.
Hong E.J., Choi D.G., Shim M.S. Targeted and effective photodynamic therapy for cancer using functionalized nanomaterials. Acta Pharm. Sin.
B(2016) 6: 297-307.
XiaoL., Gu L., HowellS.B., SailorM.J. Poroussilicon nanoparticlephotosensitizersforsingletoxygenand theirphototoxicityagainstcancercells. ACSNano
(2011) 5(5): 3651-3659.
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