Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids As a New Class of Antimycobacterial Agents

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Oct 13

PMID 34641567

Citations 2

Authors

Negar Maafi

Abdullah Al Mamun

Ondrej Jandourek

Jana Marikova

Katerina Breiterova

Adela Diepoltova

Klara Konecna

Anna Hostalkova

Daniela Hulcova

Jiri Kunes

Eliska Kohelova

Darja Koutova

Marcela Safratova

Lucie Novakova

Lucie Cahlikova

Affiliations

Soon will be listed here.

Abstract

The search for novel antimycobacterial drugs is a matter of urgency, since tuberculosis is still one of the top ten causes of death from a single infectious agent, killing more than 1.4 million people worldwide each year. Nine Amaryllidaceae alkaloids (AAs) of various structural types have been screened for their antimycobacterial activity. Unfortunately, all were considered inactive, and thus a pilot series of aromatic esters of galanthamine, 3--methylpancracine, vittatine and maritidine were synthesized to increase biological activity. The semisynthetic derivatives of AAs were screened for their in vitro antimycobacterial activity against H37Ra and two other mycobacterial strains (, ) using a modified Microplate Alamar Blue Assay. The most active compounds were also studied for their in vitro hepatotoxicity on the hepatocellular carcinoma cell line HepG2. In general, the derivatization of the original AAs was associated with a significant increase in antimycobacterial activity. Several pilot derivatives were identified as compounds with micromolar MICs against H37Ra. Two derivatives of galanthamine, and , were selected for further structure optimalization to increase the selectivity index.

Citing Articles

Investigation of the antimycobacterial activity of African medicinal plants combined with chemometric analysis to identify potential leads.

Moyo P, Ofori M, Bodede O, Wooding M, Khorommbi N, McGaw L Sci Rep. 2024; 14(1):14660.

PMID: 38918410 PMC: 11199645. DOI: 10.1038/s41598-024-65369-7.

Alkaloids of (Papaveraceae) and Berberine Derivatives as a New Class of Antimycobacterial Agents.

Wijaya V, Jandourek O, Kroustkova J, Hradiska-Breiterova K, Korabecny J, Sobolova K Biomolecules. 2022; 12(6).

PMID: 35740968 PMC: 9221290. DOI: 10.3390/biom12060844.

References

Newman D, Cragg G . Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod. 2016; 79(3):629-61. DOI: 10.1021/acs.jnatprod.5b01055. View

Piccaro G, Poce G, Biava M, Giannoni F, Fattorini L . Activity of lipophilic and hydrophilic drugs against dormant and replicating Mycobacterium tuberculosis. J Antibiot (Tokyo). 2015; 68(11):711-4. DOI: 10.1038/ja.2015.52. View

Heinrich M, Lee Teoh H . Galanthamine from snowdrop--the development of a modern drug against Alzheimer's disease from local Caucasian knowledge. J Ethnopharmacol. 2004; 92(2-3):147-62. DOI: 10.1016/j.jep.2004.02.012. View

Okunade A, Elvin-Lewis M, Lewis W . Natural antimycobacterial metabolites: current status. Phytochemistry. 2004; 65(8):1017-32. DOI: 10.1016/j.phytochem.2004.02.013. View

Marikova J, Ritomska A, Korabecny J, Perinova R, Al Mamun A, Kucera T . Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline as Selective Inhibitors of Butyrylcholinesterase. J Nat Prod. 2020; 83(5):1359-1367. DOI: 10.1021/acs.jnatprod.9b00561. View

Roy M, Liang L, Xiao X, Feng P, Ye M, Liu J . Lycorine: A prospective natural lead for anticancer drug discovery. Biomed Pharmacother. 2018; 107:615-624. PMC: 7127747. DOI: 10.1016/j.biopha.2018.07.147. View

Perinova R, Maafi N, Korabecny J, Kohelova E, De Simone A, Al Mamun A . Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer's disease. Bioorg Chem. 2020; 100:103928. DOI: 10.1016/j.bioorg.2020.103928. View

Phelan J, Maitra A, McNerney R, Nair M, Gupta A, Coll F . The draft genome of Mycobacterium aurum, a potential model organism for investigating drugs against Mycobacterium tuberculosis and Mycobacterium leprae. Int J Mycobacteriol. 2016; 4(3):207-16. DOI: 10.1016/j.ijmyco.2015.05.001. View

Nair J, Wilhelm A, Bonnet S, van Staden J . Antibacterial constituents of the plant family Amaryllidaceae. Bioorg Med Chem Lett. 2017; 27(22):4943-4951. DOI: 10.1016/j.bmcl.2017.09.052. View

10.

Mishra S, Tripathi G, Kishore N, Singh R, Singh A, Tiwari V . Drug development against tuberculosis: Impact of alkaloids. Eur J Med Chem. 2017; 137:504-544. DOI: 10.1016/j.ejmech.2017.06.005. View

11.

Copp B, Pearce A . Natural product growth inhibitors of Mycobacterium tuberculosis. Nat Prod Rep. 2007; 24(2):278-97. DOI: 10.1039/b513520f. View

12.

Koul A, Arnoult E, Lounis N, Guillemont J, Andries K . The challenge of new drug discovery for tuberculosis. Nature. 2011; 469(7331):483-90. DOI: 10.1038/nature09657. View

13.

Kishore N, Mishra B, Tripathi V, Tiwari V . Alkaloids as potential anti-tubercular agents. Fitoterapia. 2009; 80(3):149-63. DOI: 10.1016/j.fitote.2009.01.002. View

14.

Al Mamun A, Marikova J, Hulcova D, Janousek J, Safratova M, Novakova L . Amaryllidaceae Alkaloids of Belladine-Type from cv. Carlton as New Selective Inhibitors of Butyrylcholinesterase. Biomolecules. 2020; 10(5). PMC: 7277649. DOI: 10.3390/biom10050800. View

15.

Koutova D, Maafi N, Havelek R, Opletal L, Blunden G, Rezacova M . Chemical and Biological Aspects of Montanine-Type Alkaloids Isolated from Plants of the Amaryllidaceae Family. Molecules. 2020; 25(10). PMC: 7288066. DOI: 10.3390/molecules25102337. View

16.

Kohelova E, Perinova R, Maafi N, Korabecny J, Hulcova D, Marikova J . Derivatives of the β-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer's Disease. Molecules. 2019; 24(7). PMC: 6480460. DOI: 10.3390/molecules24071307. View

17.

McLachlan A, Kekre N, McNulty J, Pandey S . Pancratistatin: a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis. Apoptosis. 2005; 10(3):619-30. DOI: 10.1007/s10495-005-1896-x. View

18.

Tiberi S, Munoz-Torrico M, Duarte R, Dalcolmo M, DAmbrosio L, Migliori G . New drugs and perspectives for new anti-tuberculosis regimens. Pulmonology. 2018; 24(2):86-98. DOI: 10.1016/j.rppnen.2017.10.009. View

19.

Griffin C, Karnik A, McNulty J, Pandey S . Pancratistatin selectively targets cancer cell mitochondria and reduces growth of human colon tumor xenografts. Mol Cancer Ther. 2011; 10(1):57-68. DOI: 10.1158/1535-7163.MCT-10-0735. View

20.

Patridge E, Gareiss P, Kinch M, Hoyer D . An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov Today. 2015; 21(2):204-7. DOI: 10.1016/j.drudis.2015.01.009. View