Alkaloids

Submitted By: Ananya Azad Hrisha- 1558

Alkaloids

Alkaloids are basic (alkali-like), nitrogen-containing organic constituents found in some plants. They give

positive responses with Dragendorff, Mayer, Hager and Wagner reagents .Alkaloids are organic bases.

Many alkaloids are poisonous, others are addictive (e.g. cocaine), and some are used clinically (e.g.

morphine). More than 10 000 alkaloids are now known, the first discovered being narcotine, isolated from

opium by Derosne in 1803. (Plant Alkaloids, Jack G Woolley) 1

Alkaloids are normally classified according to the heterocyclic ring system they possess, but some authors

prefer a classification based on their biosynthetic origins from amino acids, e.g. phenylalanine, tyrosine or

tryptophan. (Justin et al.)2 Many individual names are formed by adding the suffix "-ine" to the species or

generic alkaloids. For example, atropine is isolated from the plant Atropa belladonna, strychnine is obtained

from the seed of Strychnine tree.4 Alkaloids are important chemical compounds that serve as a rich reservoir

for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis

effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and

vinblastine, have already been successfully developed into anticancer drugs. (Jin-Jian Lu et al., 2012)3.

Classification of Alkaloids

Currently, alkaloids are classified according to both chemical structure and origin. In Table 1 an

alkaloid classification is presented. (Emin Cadar et al., 2015)5

Table-1: Alkaloid classification according to structure of derivatives Group Representatives

Tropane derivatives Atropine, cocaine, ecgonine, scopolamine

Isoquinoline derivatives Opium alkaloids, morphine, codeine, thebaine,

papaverine, narcotine, sanguinarine, narceine,

hydrastiane, berberine

Quinoline derivatives Quinine, quinidine, dihydroquinone,

dihyrdoqunidine, strychnine, brucine, veratrine,

cevadine

Pyridine derivatives Piperine, coniine, trigonelline, arecaidine,

guvacine, pilocarpine, cytosine, nicotine,

sparteine, pelletierine

Pyrolidine derivatives Hygrine, cuschygrine, nicotine

Terpeness From aconite: aconitine

Sterols: solanine, samandarine

Betaine derivatives (with quaternary azoth) Muscarine, choline, neurine

Phenethylamine derivatives Mescalime, ephedrine

Indole derivatives Tryptamie derivatives: dimethyltryptamine

(DMT), NMT, psilocybin, serotonin, melatonin

Ergolines: alkaloids originating from ergot:

ergine, ergotamine, lyseric acid, and so on.;

derivatives of lysergic acid (LSD)

Beta-carbolines: harmine, yohimbine, reserpină,

emetine

Purine derivatives Xanthine derivatives: caffeine, theobromine,

theophylline

Alkaloids are often divided into the following major groups: (Anonymous)

1. "True alkaloids”: which contain nitrogen in the heterocycle and originate from amino acids. Their

characteristic examples are atropine, nicotine and morphine. This group also includes some alkaloids which

beside nitrogen heterocycle contain terpene (e.g. evonine) or peptide fragments (e.g. ergotamine). This

group also includes piperidine alkaloids coniine and coniceine although they do not originate from amino

acids.

2. "Protoalkaloids”: which contain nitrogen and also originate from amino acids. Examples include

mescaline, adrenaline and ephedrine.

3. Polyamine alkaloids: derivatives of putrescine, spermidine and spermine.

4. Peptide and cyclopeptide alkaloids.

5. Pseudalkaloids: alkaloid-like compounds which do not originate from amino acids. This group includes,

terpene-like and steroid-like alkaloids, as well as purine-like alkaloids such as caffeine, theobromine and

theophylline. Some authors classify as pseudoalkaloids such compounds such as ephedrine and cathinone.

Those originate from the amino acid phenylalanine, but acquire their nitrogen atom not from the amino acid

but through transamination.

Table-2: Brief description on Alkaloids

Alkaloid Name Source (Genus/Family)

Source Type &

Inhabitant

Therapeutic Uses

Qunine

Cinchona bark,

extract

Family: Rubeceae1

Genus: Cinchona

Cinchona

calisaya Wedd.

(1848)

Cinchona

officinalis L.

(1753)

Cinchona

pubescens Vahl

(1790)

Tree,

medicinal

plant.

They are native

to the

tropical Andea

n forests of

western South

America.

(Motley and

Cheryl, 2010)6.

Antimalarial1, anti-

pyretic, and slight

analgesic.5

Can be used in

persistent febrile

states, migraine.5

Qunidine Antiarrhythmic (heart)

Vinblastine Periwinkle plant

Catharanthus roseus

and other vinca

plants.

Subshrub

Component of a

number

of chemotherapy

regimens

also used to treat

histiocytosis.7

Vinca

Alkal

oids

Vincristine

Genus: Catharanthus

Family: Apocynaceae

Endemic to

Madagascar Delivered

via intravenous infusi

on for use in various

types

of chemotherapy

regimens

Occasionally used as

an immunosuppressa

nt, for example, in

treating thrombotic

thrombocytopenic

purpura(TTP) or

chronic idiopathic

thrombocytopenic

purpura (ITP).8

Vindesine Is an anti-

mitotic vinca

alkaloid used

in chemotherapy.

Used to treat many

different types of

cancer, including

leukaemia, lymphom

a, melanoma, breast

cancer, and lung

cancer.

Vinorelbine Chemotherapy

medication used to

treat a number of

types of cancers like

breast cancer, non-

small cell lung

cancer.

Also active

in rhabdomyosarcom

a.9

Codeine Obtained from poppy

plant Papaver

somniferum

Genus: Papaver

Family: Papaveraceae

Annual herb.

Native range

is probably the

eastern

Mediterranean

.

.

Used as a central

analgesic, sedative,

hypontic,

antinonciceptive,

antiperistaltic.10

Suppress both

artificially induced

and disease-related

cough.11

Widely used as anti-

tussivedrug.12

Morphine Primary source of

morphine is isolation

Annual herb.

Used to treat acute

and chronic pain.5

Vin

ca

Alk

aloi

ds

from poppy straw of

the opium poppy.13

Genus: Papaver

Family: Papaveraceae

Native range

is probably the

eastern

Mediterranean

.

.

Immediate-release

morphine is

beneficial in reducing

the symptom

of shortness of

breath due to

both cancer and

noncancer causes.14,15

Sustained-release

morphine

significantly reduces

breathlessness safely,

with its benefits

maintained over

time.16,17

Papaverine Papaverine is

extracted from the

milky juice of raw

poppy capsules

(opium).5

Genus: Papaver

Family: Papaveraceae

Annual herb.

Native range

is probably the

eastern

Mediterranean

.

An

opiumalkaloidantispa

smodic drug, used

primarily in the

treatment of visceral

spasm, vasospasm

(especially those

involving the heart

and the brain), and

occasionally in the

treatment of erectile

dysfunction.

Effect is exerted

directly on smooth

muscles.5

Strychnine The strychnine

tree (Strychnos nux-

vomica L.), also

known as nux

vomica, poison

nut, semen

strychnos and quaker

buttons.

Genus: Strychnos

Family: Loganiaceae

A deciduous tr

opicaltree nati

ve to India,

and southeast

Asia.

Very toxic.

Convulsant.2

Effective in digestive

problems, different

types of pains etc.

Atropine Datura

stramonium L.

(syn. D. inermis).

Datura anoxia

Atropa

belladonna

Herbaceo

us,

leafy annu

als and

short-

lived pere

nnial.

Atropine is used as

an antidote in

muscarine

intoxications.5

In ophthalmology, it

is used for pupil

dilation (mydriasis)

Mandragora

officinarum

Genus: Datura

Family: Solanaceae

Believed

to have

originated

in Mexico,

but has

now

become

naturalize

d in many

other

regions.

in ocular

examinations.5

Competitive

antagonist of

muscarinic

acetylcholine

receptors.2

Anti-cholinergic,

anti-myopia effects.2

Berberine

Berberis species,

Hydrastis,

Canadensis,

Xanthorhiza

simplicissima,

Phellodendron

amurense, Coptis

chinensis, Tinospora

cordifolia, Argemone

mexicana and

Eschscholzia

californica

Many

plants/trees of

various places.

Anti inflammatory,

anti bacterial/viral,

recently experiments

showed anti diabetic

and beneficial effects

on cardiovascular

system and anti

cancer and others

disorders such as

intestinal2

Cytisine (baptitoxine, sophorine)

Labum and Cytisus of

Family: Fabaceae

Shrub

Native to

western and

central

Europe.

Acetylcholine

agonist, smoking

cessation drug.

Nicotine

Nicotiana

tobacum

Genus: Nicotiana

Family: Solanaceae

Forb/herb

Originated in

the tropical

Americas

(South

America,

Mexico, and

the West

Indies)

Stimulant,

antiherbivore,

insectide, anti-

inflammatory.2

Caffeine Found in coffee, tea,

cola nuts, mate,

guarana, and cocoa.

Stimulant of the

CNS, increase of

pulse and arterial

blood pressure,

bronchial dilator,

stimulant of intestinal

peristalsis.

Reference:

1. Plant Alkaloids Jack G Woolley, De Montfort University, Leicester, UK

2. Plant Secondary Metabolites: Biosynthesis, Classification, Function and Pharmacological

Properties Justin N. Kabera1 , Edmond Semana1 , Ally R. Mussa1 and Xin He1, 2

1) Department of Pharmacology, School of Chinese Materia Medica, Tianjin University of

Traditional Chinese Medicine, Tianjin 300193, China

2) Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, China

3. Review Article: Alkaloids Isolated from Natural Herbs as the Anticancer Agents, Jin-Jian Lu, Jiao

Lin Bao, Xiu-Ping Chen, Min Huang, and Yi-Tao Wang, State Key Laboratory of Quality Research

in Chinese Medicine (University of Macau) and Institute of Chinese Medical Sciences, University

of Macau, Avenue Padre Toma’s Pereira, Taipa 999078, Macao, China, Received 11 May 2012;

Revised 17 July 2012; Accepted 30 July 2012, Academic Editor: Alvin J. Beitz, Copyright © 2012

Jin-Jian Lu et al.

4. Chemical Encyclopedia: http://www.xumuk.ru/encyklopedia/119.html

Emetine

Ipecac

Cephalelisipecacuan

ha A. Rich. (Rio

Ipecac)

and

C. acuminata H. Karst

(Cartagena ipecac).

Family: Rubiaceae

Shrubby plant.

Grows in

Brazilian

rainforests and

other locations

in Central and

South

America.

Ipecac is used in the

treatment of

poisoning by

induction of emesis

and production of

expectoration.

Ipecac syrup

(Clinical

applications)-Ipecac

syrup is used to

induce vomiting,

after the ingestion of

toxic compounds or

after a drugs

overdose.18

Cephaeline

SORBICILLACTONE-A

Salt-water culture of

a Penicillium

chrysogenum

strain isolated from a

specimen of the

Mediterranean

sponge

Irciniafasciculata.19,20

Mediterranean

. Active against

leukemia cells

without showing

notable

cytotoxicity.21

Has anti-tumour, antiviral and

neuroprotective

properties.22,23,24

5. The Impact of Alkaloids Structures from Natural Compounds on Public Health, Emin Cadar (Umf

Carol Davila Bucharest, Faculty of Pharmacy), Str. Traian Vuia (Nr. 6, Sector 2, Bucharest,

Romania); Aneta Tomescu (Corresponding Author, Tomescu.Aneta@Gmail.com, Ovidius

University of Constanta, Faculty Of medicine, Campus Corp B, University Alley Nr. 1, Constanta,

Romania); Cristina-Luiza Erimia (Ovidius University of Constanta, Faculty of Pharmacy, Campus

Corp B, University Alley Nr. 1, Constanta, Romania); Alef Mustafa (Ovidius University of

Constanta, Faculty of Pharmacy, Campus Corp B, University Alley Nr. 1, Constanta, Romania);

Rodica Sîrbu (Ovidius University of Constanta, Faculty of Pharmacy, Campus Corp B, University

Alley Nr. 1, Constanta, Romania); ISSN 2411-9563 (Print); ISSN 2312-8429 (Online); European

Journal of Social Sciences Education and Research; Sep – Dec 2015 Vol 5, Nr. 1.

6. Motley, Cheryl. "Cinchona and its product--Quinine". Ethnobotanical leaflets. Southern Illinois

University Herbarium. Retrieved 11 June 2010.

7. Vinblastine Sulfate. The American Society of Health-System Pharmacists. Retrieved Jan 2, 2015

8. Brayfield, A, ed. (13 December 2013). "Vincristine". Martindale: The Complete Drug Reference.

Pharmaceutical Press. Retrieved 15 April 2014.

9. Casanova, M; Ferrari, A; Spreafico, F; Terenziani, M; Massimino, M; Luksch, R; Cefalo, G;

Polastri, D; et al. (2002). "Vinorelbine in previously treated advanced childhood sarcomas:

Evidence of activity in rhabdomyosarcoma". Cancer. 94 (12): 3263–

8.doi:10.1002/cncr.10600. PMID 12115359.

10. Recent updates on codeine by Monika Bhandari, Anil Bhandari, and Aakanksha Bhandari, Pharm

Methods. 2011 Jan-Mar; 2(1): 3–8, doi: 10.4103/2229-4708.81082, PMCID: PMC3658028

11. Matthys H, Bleicher B, Bleicher U(1983) Dextromethorphan and codeine: objective assessment of

antitussive activity in patients with chronic cough. J Int Med Res. 11:92–100.

12. Dayer P, Desmeules J, Leemann T, Striberni R. Bioactivation of the narcotic drug codeine in human

liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation

(cytochrome P-450 dbl/bufI). BiochemBiophys Res Commun 1988; 152: 411–416.

13. Narcotic Drugs Estimated World Requirements for 2008, Statistics for 2006. New York: United

Nations Pubns. 2008. p. 77. ISBN 9789210481199.

14. Schrijvers D, van Fraeyenhove F (2010). "Emergencies in palliative care". Cancer J. 16(5): 514–

20. doi:10.1097/PPO.0b013e3181f28a8d. PMID 20890149.

15. Naqvi F, Cervo F, Fields S (August 2009). "Evidence-based review of interventions to improve

palliation of pain, dyspnea, depression". Geriatrics. 64 (8): 8–10, 12–4. PMID 20722311.

16. Mahler DA, Selecky PA, Harrod CG, Benditt JO, Carrieri-Kohlman V, Curtis JR, Manning HL,

Mularski RA, Varkey B, Campbell M, Carter ER, Chiong JR, Ely EW, Hansen-Flaschen J,

O'Donnell DE, Waller A (March 2010). "American College of Chest Physicians consensus

statement on the management of dyspnea in patients with advanced lung or heart

disease". Chest. 137 (3): 674–91. doi:10.1378/chest.09-1543. PMID 20202949.

17. Mattick RP; Digiusto E; Doran C; O’Brien S; Kimber J; Henderson N; Breen B; Shearer J;

Gates J; Shakeshaft A; NEPOD Trial Investigators (2004). National Evaluation of

Pharmacotherapies for Opioid Dependence (NEPOD): Report of Results and

Recommendation (PDF). Monograph Series No. 52. Australian Government. ISBN 0-642-82459-

2.

18. Alexander J. German, Jill E. Maddison, Grant Guilford, in Small Animal Clinical Pharmacology

(Second Edition), 2008.

19. Bringmann G, Lang G, Mühlbacher J, Schaumann K, Steffens S, Rytik PG, Hentschel U,

Morschhäuser J, Brun R. In: Sponges (Porifera) Müller WEG, editor. Vol. 1. Springer; Berlin:

2003. pp. 231–253.

20. Bringmann G, Lang G, Gulder TAM, Hideyuki H, Mühlbacher J, Maksimenka K, Steffens S,

Schaumann K, Stöhr R, Wiese J, Imhoff JF, Perovi-Ottstadt S, Boreiko O, Müller WEG. The first

sorbicillinoid alkaloids, the antileukemicsorbicillactones A and B, from a sponge derived

Penicilliumchrysogenum strain. Tetrahedron. 2005;61:7252–7265.

21. Large-Scale Biotechnological Production of the Antileukemic Marine Natural Product

Sorbicillactone A, Gerhard Bringmann,1,* Tobias A. M. Gulder,1 Gerhard Lang,1,2

Stefanie Schmitt,1 Rüdiger Stöhr,2 Jutta Wiese,2 Kerstin Nagel,2 and Johannes F.

Imhoff2,*Mar Drugs. 2007 Jun; 5(2): 23–30.Published online 2007 Jun 25. PMCID:

PMC2365691.

22. Bringmann G, Lang G, Gulder TAM, Hideyuki H, Mühlbacher J, Maksimenka K, Steffens

S, Schaumann K, Stöhr R, Wiese J, Imhoff JF, Perovi-Ottstadt S, Boreiko O, Müller WEG.

The first sorbicillinoid alkaloids, the antileukemicsorbicillactones A and B, from a sponge

derived Penicilliumchrysogenum strain. Tetrahedron. 2005;61:7252–7265.

23. Bringmann G, Lang G, Mühlbacher J, Schaumann K, Steffens S, Müller WEG.

Sorbicillactone A derivatives for the treatment of tumor and viral diseases. International

Patent Application. WO 2004/026854. 1.4.2004.

24. SORBICILLACTONE-A DERIVATIVES FOR THE TREATMENT OF TUMOUR AND VIRAL

DISEASES, No.: WO/2004/026854, International Application No.: PCT/EP2003/007805,

Publication Date: 01.04.2004, International Filing Date: 17.07.2003, Chapter 2, Demand Filed: