Presentation on theme: "بسم الله الرحمن الرحيم PHG 322 Pharmacogonsy II lecture 2 Presented by Assistant Prof. Dr. Ebtesam Alsheddi."— Presentation transcript:
1 بسم الله الرحمن الرحيمPHG 322 Pharmacogonsy II lecture 2 Presented by Assistant Prof. Dr. Ebtesam Alsheddi
2 Stability: hot dil. acids or conc. mineral acids may cause: Generally alkaloids are decomposed by heatexcept:caffeinesublimes without decompositionEffect of Acids:hot dil. acids or conc. mineral acids may cause:DehydrationO-demethylationNext page !e.g.codeineapoalkaloidsconc HClor HIe.g.morphineapomorphinemorphine+ CH3Cl or CH3I
3 Stability: (cont.) hot dil. acids or conc. mineral acids may cause: Effect of Acids: (cont.)hot dil. acids or conc. mineral acids may cause:Hydrolysis of- glucoalkaloids:- ester alkaloids:e.g.solaninee.g.atropine
4 Effect of strong alkalies liberate most alkaloids from their salts Stability: (cont.)Effect of Alkalies:Effect ofweak alkaliesEffect of strong alkaliesEffect ofhot dil. alkaliesliberate most alkaloids from their saltsform salts with alkaloidscontaining carboxylic groupe.gNarceine + NaHCO3Na salt
5 hydrolysis of ester alkaloids b) Effect of strong alkalies:salt(phenates)phenolic alkaloid+ aq. NaOH or KOHc) Effect of hot dilute alkalies:hydrolysis of ester alkaloidscleavage of lactone ringcorresponding acide.g.atropinee.g. pilocarpinePilocarpic acid
6 Precipitation reactions precipitating reagent (contains heavy metals Tests for identification:include two types of reactions:Precipitation reactionsColour reactions1) Precipitation reactions:precipitating reagentaqueous soln. ofalkaloidal salts+(contains heavy metalse.g. Hg, Cd, Bi, …)Coloured ppts(amorphous or crystalline)N.B.certain alkaloids do not react e.g. caffeinefalse positive results are possiblemost reagents precipitate: proteins, tannins, …
9 - specific forone alkaloid or a group of related alkaloid:1) Vitalis test forsolanaceous alkaloids:+ conc HNO3 & alc. KOHviolet colour2) Van-Urks test for ergot alkaloids:+ PDAB in conc H2SO4blue colour
10 Pharmacological activity N.B.+ ve with:- most alkaloidsPharmacological activity:wide range of pharmacological activitiesPharmacological activityAlkaloidAnalgesic & narcoticsMorphineAnti-tussiveCodeineCNS stimulantCaffeine & strychnineMydriaticAtropineAnticancerVincristine, vinblastine, taxol10
11 Chemical classification: Non-heterocyclicHeterocyclic= Atypical alkaloids(Protoalkaloids)= typical alkaloids14 major groupsaccording to ring structure
12 Pyridine nucleus + another nitrogenous ring Alkaloids of the Pyridine nucleus:classified according to building nucleus into:Pyridine nucleus onlyPyridine nucleus another nitrogenous ringTetrahydro-pyridinenucleusPiperidinenucleusPyridonenucleus12
13 1) Pyridine alkaloids containing another nitrogenous ring: e.g. Tobacco alkaloidsnon-volatileliquidVolatileliquids(-)-nicotine (major)nicoteinenor-nicotine
14 Nicotine Colour tests 2 basic N atoms form salts with acids Properties:air or lightColourless or pale yellow oily liquidbrownless basicColour testsaq. soln +PDAB2 basic N atomsrose red colourform salts with acidsviolet colourgraduallyTests:nicotine +picric acidCrystals
15 respiratory stimulant Pharmacological actions & uses:due tohigh toxicityLittle use in medicineIn small dosesrespiratory stimulantIn larger dosesrespiratory depressantIncreases incidence of abortionMain use:Insecticide & anthelmintic in veterinary medicine
16 2) Piperidine alkaloids: e.g. alkaloids of:a) Black pepperb) Coniumc) Lobeliad) Pomogranatea) Pepper alkaloids:Occurrence: fruits of Piper species e.g. P. nigrumMajor alkaloid: piperine+ acidIt is very weak basicNo saltColour tests+ H2SO4Red colour
18 Uses: Chronic toxicity: Mainly as condiment Little use in medicineUsed in rubefacient preparationsChronic toxicity:Prologed use at high dosesloss of taste buds in tongue
19 c- Lobelia alkaloidsOccurrence: the dried aerial parts of Lobelia inflata.(indian tobacoo) Major alkaloid: Lobeline crystalline)
20 Uses: -Asthma -Chronic bronchitis -Anti-smoking preparations -Injection of lobeline hydrochloride is used in the resuscitation of newborn infants. Caution: Toxic doses the herb has a paralytic effect
21 d- Pomegranate alkaloid Occurrence: the fruit rind, root bark and stem bark of Punica granata Major alkaloid: pelltierine (liquid) pelletierine tannate (mixture, solid) Alkali decompose it to give free alkaloidsPomegranates have astringent properties because of the alkaloids (pelletierine tannate) present in the bark of the stems and roots and have been used for many years as an anthelmintic: removing tapeworms
22 II. Alkaloids of the Quinoline group Most important → Cinchona alkaloidsCinchona alkaloidsPresent in the bark Cinchona species- Cinchona ledgeriana & C. calisaya (yellow Cinchona)- C. succirubra (red Cinchona) F. Rubiaceaee.g. of alkaloids: two groups of stereoisomers:Quinine (l) & Quinidine (d)Cinchonidine (l) & Cinchonine (d)> 50%
23 Cinchonine & cinchonidine Quinine (Cinchonidine epimer at C-9)Quinidine (Cinchonine epimer at C-9)Structure:RAlkaloidHCinchonine & cinchonidineOCH3Quinine & quinidine(few drops till yellow colour appears)Quinine:Intensely bitter solid
24 1) Fluorescence test: + dil H2SO4 Fluorescence Quinine (l) gives Quinidine (d) among other products when warmed with KOH in amyl alcoholCinchonine & Cinchonidine are less soluble in H2O than quinine & quinidineTest:1) Fluorescence test: + dil H2SO4Fluorescence+ ve for quinine & quinidine2) Thalleoquine test:aq. soln of alkaloidal salt +Br2/H2O+ NH4OHEmerald green colour
25 Uses: Quinine (contra indicated in pregnancy as it causes abortion) as Quinine sulphate or other saltsused asanti-malarialhas febrifuge effect(contra indicated in pregnancy as it causes abortion)used asQuinidinecardiac depressant (anti-arrythmic)Cinchonine and Cinchonidine are used as anti-rheumatic
26 Structure activity relationship: For antimalarial activity (Quinine):- Removal of vinyl grouploss of activity- Replacement of CHOH by:- CHCl, CH2, COdecreases activityVinyl group
27 III. Alkaloids of the Isoquinoline group IpecacuanhaOpium(Papaverine type)
28 Isoquinoline Alkaloids 1- Ipecacuanha Alkaloids Occurrence:Ipecac is the dried roots and rhizomes of Cephalis ipecacuanha (Brazilian ipecacuanha) or Cephalis acuminata (Cartagena or Panama ipecacuanha) Fam. Rubiaceae.It contains several alkaloids (2 –2.5 %), mainly emetine ( % of total alkaloids), with cephaline and psychotrine.
29 It is non phenolic and levorotatory. It contains 2 basic nitrogens. Emetine:It is non phenolic and levorotatory.It contains 2 basic nitrogens.Cephaline:It is phenolic and levorotatory.It gives emetine on methylation with (CH3)2 SO4.Psychotrine:Occurs as yellow prisms.It is phenolic and gives cephaline on reduction.It gives emetine on reduction followed by methylation.
30 Tests for identification of Ipeca alkaloids: Alkaloidal solution in HCl + Ca hypochlorite orange color.Emetine and cephaline + Froehd's reagent: dirty green color (the color with emetine fades by addition of HCl).Psychotrine + Froehd's reagent: pale green color.Cephaline and psychotrine + p-nitrodiazobenzene dye soluble in NaOH purple color.Psychotrine + conc. H2SO4 + HNO3 cherry red color.Emetine + Liebermann's reagent black color.
31 Uses:Emetine and cephaeline have antitumour and antiviral activity, but are too toxic for therapeutic use.Emetine and psychotrine are mainly used as emetic drugs.The crude drug is used as expectorant (due to its saponin content) .Emetine HCl has an antiamoebic effect, and are used for the treatment of amoebic dysentry and Fasciola.Ipeca alkaloids are diaphoretic, alone or in combination with opium (e.g. Dover's powder).