Marine Alkaloids As Bioactive Agents Against Protozoal Neglected Tropical Diseases and Malaria

Overview

Journal Nat Prod Rep

Publisher Royal Society of Chemistry

Date 2021 Dec 16

PMID 34913053

Citations 15

Authors

Andre G Tempone

Pauline Pieper

Samanta E T Borborema

Fernanda Thevenard

Joao Henrique G Lago

Simon L Croft

Edward A Anderson

Affiliations

Soon will be listed here.

Abstract

Covering: 2000 up to 2021Natural products are an important resource in drug discovery, directly or indirectly delivering numerous small molecules for potential development as human medicines. Among the many classes of natural products, alkaloids have a rich history of therapeutic applications. The extensive chemodiversity of alkaloids found in the marine environment has attracted considerable attention for such uses, while the scarcity of these natural materials has stimulated efforts towards their total synthesis. This review focuses on the biological activity of marine alkaloids (covering 2000 to up to 2021) towards Neglected Tropical Diseases (NTDs) caused by protozoan parasites, and malaria. Chemotherapy represents the only form of treatment for Chagas disease, human African trypanosomiasis, leishmaniasis and malaria, but there is currently a restricted arsenal of drugs, which often elicit severe adverse effects, show variable efficacy or resistance, or are costly. Natural product scaffolds have re-emerged as a focus of academic drug discovery programmes, offering a different resource to discover new chemical entities with new modes of action. In this review, the potential of a range of marine alkaloids is analyzed, accompanied by coverage of synthetic efforts that enable further studies of key antiprotozoal natural product scaffolds.

Citing Articles

An integrated theoretical study on natural alkaloids as SARS-CoV-2 main protease inhibitors: a step toward discovery of potential drug candidates with anti-COVID-19 activity.

Parveen S, Shahbaz L, Shafiq N, Rashid M, Mohany M, Zhu M RSC Adv. 2025; 15(3):2045-2065.

PMID: 39845115 PMC: 11751704. DOI: 10.1039/d4ra06536k.

Anthelmintic Potential of Conjugated Long-Chain Fatty Acids Isolated from the Bioluminescent Mushroom .

Oliveira M, Dos S Andrade T, Junior J, Lima N, Machado H, Tabudravu J J Nat Prod. 2025; 88(2):255-261.

PMID: 39754587 PMC: 11877520. DOI: 10.1021/acs.jnatprod.4c00546.

and Leishmanicidal Activity of Beauvericin.

de Oliveira Filho V, Gubiani J, Borgonovi V, Hilario F, de Amorim M, Minori K J Nat Prod. 2024; 87(12):2829-2838.

PMID: 39626110 PMC: 11686502. DOI: 10.1021/acs.jnatprod.4c01098.

Aurantoside L, a New Tetramic Acid Glycoside with Anti-Leishmanial Activity Isolated from the Marine Sponge .

Oyadomari Y, Goto Y, Suganuma K, Kawazu S, Becking L, Fusetani N Mar Drugs. 2024; 22(4).

PMID: 38667788 PMC: 11050911. DOI: 10.3390/md22040171.

A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase.

Zhang K, Liang J, Zhang B, Huang L, Yu J, Xiao X Molecules. 2024; 29(5).

PMID: 38474490 PMC: 10934704. DOI: 10.3390/molecules29050978.

References

Balana-Fouce R, Perez Pertejo M, Dominguez-Asenjo B, Gutierrez-Corbo C, Reguera R . Walking a tightrope: drug discovery in visceral leishmaniasis. Drug Discov Today. 2019; 24(5):1209-1216. DOI: 10.1016/j.drudis.2019.03.007. View

Barbe G, Charette A . Total synthesis of (+)-lepadin B: stereoselective synthesis of nonracemic polysubstituted hydroquinolines using an RC-ROM process. J Am Chem Soc. 2008; 130(42):13873-5. DOI: 10.1021/ja8068215. View

Gros E, Al-Mourabit A, Martin M, Sorres J, Vacelet J, Frederich M . Netamines H-N, tricyclic alkaloids from the marine sponge Biemna laboutei and their antimalarial activity. J Nat Prod. 2014; 77(4):818-23. DOI: 10.1021/np4009283. View

Berninger M, Schmidt I, Ponte-Sucre A, Holzgrabe U . Novel lead compounds in pre-clinical development against African sleeping sickness. Medchemcomm. 2018; 8(10):1872-1890. PMC: 6072528. DOI: 10.1039/c7md00280g. View

Kratz J, Bournissen F, Forsyth C, Sosa-Estani S . Clinical and pharmacological profile of benznidazole for treatment of Chagas disease. Expert Rev Clin Pharmacol. 2018; 11(10):943-957. DOI: 10.1080/17512433.2018.1509704. View

Wells T . Natural products as starting points for future anti-malarial therapies: going back to our roots?. Malar J. 2011; 10 Suppl 1:S3. PMC: 3059461. DOI: 10.1186/1475-2875-10-S1-S3. View

Miyake F, Yakushijin K, Horne D . A concise synthesis of topsentin A and nortopsentins B and D. Org Lett. 2000; 2(14):2121-3. DOI: 10.1021/ol000124g. View

Osei E, Kwain S, Mawuli G, Anang A, Baffour-Awuah Owusu K, Camas M . Paenidigyamycin A, Potent Antiparasitic Imidazole Alkaloid from the Ghanaian sp. DE2SH. Mar Drugs. 2018; 17(1). PMC: 6356793. DOI: 10.3390/md17010009. View

Souto E, Dias-Ferreira J, Craveiro S, Severino P, Sanchez-Lopez E, Garcia M . Therapeutic Interventions for Countering Leishmaniasis and Chagas's Disease: From Traditional Sources to Nanotechnological Systems. Pathogens. 2019; 8(3). PMC: 6789685. DOI: 10.3390/pathogens8030119. View

10.

Santos S, de Araujo R, Giarolla J, El Seoud O, Ferreira E . Searching for drugs for Chagas disease, leishmaniasis and schistosomiasis: a review. Int J Antimicrob Agents. 2020; 55(4):105906. DOI: 10.1016/j.ijantimicag.2020.105906. View

11.

Andrews K, Fisher G, Skinner-Adams T . Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist. 2014; 4(2):95-111. PMC: 4095053. DOI: 10.1016/j.ijpddr.2014.02.002. View

12.

Cafieri F, Fattorusso E, Taglialatela-Scafati O . Novel bromopyrrole alkaloids from the sponge Agelas dispar. J Nat Prod. 1998; 61(1):122-5. DOI: 10.1021/np970323h. View

13.

Shimokawa J, Ishiwata T, Shirai K, Koshino H, Tanatani A, Nakata T . Total synthesis of (+)-batzelladine A and (-)-batzelladine D, and identification of their target protein. Chemistry. 2005; 11(23):6878-88. DOI: 10.1002/chem.200500852. View

14.

Davis R, Duffy S, Fletcher S, Avery V, Quinn R . Thiaplakortones A-D: antimalarial thiazine alkaloids from the Australian marine sponge Plakortis lita. J Org Chem. 2013; 78(19):9608-13. DOI: 10.1021/jo400988y. View

15.

Nakanishi S, Matsuda Y, Iwahashi K, Kase H . K-252b, c and d, potent inhibitors of protein kinase C from microbial origin. J Antibiot (Tokyo). 1986; 39(8):1066-71. DOI: 10.7164/antibiotics.39.1066. View

16.

Zulfiqar B, Jones A, Sykes M, Shelper T, Davis R, Avery V . Screening a Natural Product-Based Library against Kinetoplastid Parasites. Molecules. 2017; 22(10). PMC: 6151456. DOI: 10.3390/molecules22101715. View

17.

Rodenko B, Al-Salabi M, Teka I, Ho W, El-Sabbagh N, Ali J . Synthesis of marine-derived 3-alkylpyridinium alkaloids with potent antiprotozoal activity. ACS Med Chem Lett. 2014; 2(12):901-6. PMC: 4018069. DOI: 10.1021/ml200160k. View

18.

Humphrey J, Liao Y, Ali A, Rein T, Wong Y, Chen H . Enantioselective total syntheses of manzamine a and related alkaloids. J Am Chem Soc. 2002; 124(29):8584-92. DOI: 10.1021/ja0202964. View

19.

Milanowski D, Oku N, Cartner L, Bokesch H, Williamson R, Sauri J . Unequivocal determination of caulamidines A and B: application and validation of new tools in the structure elucidation tool box. Chem Sci. 2018; 9(2):307-314. PMC: 5868047. DOI: 10.1039/c7sc01996c. View

20.

Cohen F, Overman L, Sakata S . Asymmetric total synthesis of batzelladine D. Org Lett. 2000; 1(13):2169-72. DOI: 10.1021/ol991269u. View