Presentation describes the effect of positions of functional groups and structural modification in chemical compound on physiological activity in-vivo.

1. Prepared By
Shri. Prashant Shivgunde
Assistant Professor,
Infectious Diseases Department,
Maharashtra University of Health Sciences,
Mumbai

2.  Alkyl Groups
 Hydroxyl groups
 Aldehyde and Ketone groups
 Acidic groups
 Halogens
 Nitro and Nitrite groups
 Amino Groups
 Nitrile groups
 Unsaturation
 Isomerism

3.  Decrease in Activity on alkylation
 Convulsive property of ammonia
 Trimethylamine free of all these effects
 ‘llly Convulsive Property of aniline
 Other examples-
Guaiacol Veratrole

4. Salicylic Acid Methoxy benzoic acid

5.  Increase in toxicity on alkylation
 Ethers are more toxic than alcohols
 Toxicity: Resorcinol dimethylether > resorcinol
 Toxicity: Xanthine < Theobromine (N-dimethyl
derivative of xanthine) and caffeine (N-trimethyl
dervative of xanthine)

6.  Full appearance of masked properties on
alkyaltion
 Alkylation of carboxyl/ hydroxyl/amino
 Cocaine Vs its analogue acid (Inert)
Cocaine Phenazone (antipyrine)

7.  Size of alkyl group
 Diethyl ketone is a stronger hypnotic than
acetone
 Dulcin (ethyl group) 200 times more sweet than
its methyl analogue (Tasteless)

8.  Introduction of hydroxyl group in aliphatic
compound decreases physiological action
 N-propanol is more active than glycerol

9. Hexanol is more active than sorbitol

10.  Presence of -OH cause lose physiological
activity
 Hydroxycaffeine (None of the activity present as
compared to caffeine)
 Physiological activity generally decreased by
etherification, esterification and the
conditions unfavorable to ester hydrolysis
 Anchors the molecule on reactive position of cell
chemical

11.  In case of aromatic compounds hydroxyl group
increases physiological activity of compound
 Reverse to that of aliphatic compound
 Phenol more toxic and antiseptic than Benzene
 Salicylic acid (Antifungal+ Antirheumatic) compared
to benzoic acid (Antifungal)
 Addition of more hydroxyl group increase
toxicity
 Resorcinol and pyrogyllol are more toxic than phenol

12.  Aldehydes are more toxic than ketones thus
exhibit more intense biological activity
 Formaldehyde
 Simplest aldehyde
 Strong antiseptic property
 Hardening effect on the tissues
 Introduction of hydroxyl group in aldehyde
decrease physiological activity
 Glucose (Medically inert)

13.  Pharmacological activity of compounds found
similar to that of corresponding secondary
alcohols (in general posses narcotic action)
 Aliphatic ketones
 Hypnotic activity fairly well marked
 Mixed ketones
 Acetophenone is strong hypnotic
 α,β-unsaturated ketones
 Posses diuretic activity

14.  Introduction of –SO3H/ -COOH
 Decreases or completely destroys physiological
activity of parent compound
 Phenol is poisonous but benzene sulphonic acid is
harmless
 Nitrobenzene is poisonous but nitrobenzoic acid is
harmless
 Amines are toxic but amino acids are food stuffs

15.  However physiological activity loss due to
intro of acidic groups can be restored by
esterification
 Tyrosine, a phenolic aminoacid is harmless while its
ethyl ester is poisonous
 P-amino benzoic acid has no anaesthetic property but
its alkyl esters are used as local anaesthetics

16.  Negative Halogens
 Presence of halogen at non-conjugated positions-
 Increase useful as well as toxic properties (but at
different rates)
 Increase in toxicity limited as compared to increase in
useful properties
 Resulting In widening of margin of safety

17.  Generally, Hypnotic property decreases with
increase in atomic weight but antiseptic
properties increases
 E.g.-
Chemical
Formula
Atomic
weight
Hypnotic Antiseptic
CHCl3 35.4527 +++ +
CHBr3 79.904 ++ ++
CHI3 126.90447 + +++

18.  It is to be noted that Fluorine compounds are
comparatively much less physiologically
active than the corresponding other
halogens
 Reason may be their stability..

19.  Nitro group in aromatic compounds-
increases their toxicity
 E.g. – nitrobenzene, nitronaphthol,
nitrothiophene- more toxic than parent
hydrocarbons
 However, readily oxidizable group (-CH3, -
CHO) is introduced, then toxicity decreases
 E.g- p-nitrotoluene less poisonous than p-
nitrobenzene (llly, nitroaldehydes)

20.  Aliphatic nitrites have dilatation effect
whereas nitro compounds have no action.
 Strength of this effect increases from methyl
nitrite to amyl nitrite

21.  20 and 30 nitrites easily hydrolyzed to alcohol
and nitrites, therefore more powerful than
the corresponding primary nitrites.

22.  In general, amino group is toxic.
 Acylation decreases the physiological activity
 Aniline (toxic) Vs Acetanilide (febrifuge)
 Introduction of second amino group increases
the toxicity
 All the three phenylenediamines are more
poisonous than aniline

23.  Parent compound is –HCN – A strong poison
 Introduction of nitrile group give rise to –
 Nitriles (RCN)
 Isonitriles (RNC)
 Nitriles produce coma
 In aliphatics- lower nitriles more poisonous
than higher nitriles
 Isonitriles are also more poisonous (paralyse
the respiratory system)

24.  Generally, Unsaturated compunds more toxic
than corresponding satutrated compounds
 Propanol-1 – narcotic but non-poisonous
 Allyl alcohol- Strongly poisonous

25.  ‘lly acrolein, crotonaldehyde, carvone
Acrolein Crotonaldehyde
Carvone (More toxic) Menthone (less toxic)

26.  Toxicity of a compound increases with
unsaturation
 Increase in toxicity also found in other than
‘C’- compounds
 Trivalent arsenic is more poisonous than
quinquetavalent arsenic
 Mustard gas (Cl CH2CH2)2S is poisonous, but on
oxidation converted to almost harmaless and
non-toxic substance- sulphone (Cl Ch2CH2)2SO2
(oxidation increases valency of sulphur).

27.  Structural isomerism-
 Show marked difference in their physiological
activity
 Can be seen in ortho-, meta-, para-derivatives
 E.g.-
 O-hydroxybenzoic acid is physiologically active while
both p- and m- isomers are inactive
 Ordinary cocaine is local anesthetic while –cocaine
does not have this activity
 P-aminobenzene-sulphonic acid is an active drug
whereas its two other isomers are inactive.

28.  Stereoisomerism
 Both geometrical and optical isomers show
different physiological activity
 E.g.-
 Maleic acid is poisonous while fumaric acid is harmless
Maleic Acid Fumaric acid
 (-ve) adrenaline is 12 times as active as (+) form
 ‘lly, (-) nicotine is twice active as (+).