Valliappan Kannappan presented on the importance of chirality. Chirality is a key characteristic of biological molecules and life processes. Most biological macromolecules like proteins, DNA, RNA, sugars and amino acids are chiral. Many drugs are also chiral, and the biological targets they interact with are also chiral. For this reason, the specific chiral form of a drug is important. Regulatory agencies now require separation and characterization of chiral drug molecules. Many commonly used therapeutic agents are employed as single enantiomers rather than racemic mixtures for increased efficacy and safety. Chirality will continue to be an important consideration in life science research and drug development.

1. Valliappan Kannappan
Valliappan Kannappan
VALLIAPPAN K
Professor of Quality Assurance (Retd.)
Department of Pharmacy
Annamalai University
INDIA
vallikonnect@gmail.com
Importance of Chirality 2021
10 min.

2. Valliappan Kannappan
Valliappan Kannappan
S
K
E
T
C
H
 Behavior of chiral molecules
Importance of Chirality
Importance of Chirality
 Molecules of nature
 Molecules of life
Regulatory Environment
Importance of Chirality 2021
 Regulatory Environment
 Unichiral drugs employed in Drug therapy

3. Valliappan Kannappan
Valliappan Kannappan
O
L
D
C
H
I
R
A
L
D
R
unichiral / homochiral
unichiral / homochiral-
-
Hallmark of many molecules from nature
Look @ Molecules of
@ Molecules of Nature
Nature -
- is not even-handed
(-)-morphine
N
H3C
H
32
16
N
Importance of Chirality 2021
R
U
G
S
(5R,6S,9R,13S,14R) - analgesic
Of the possible 32 stereoisomers only
the levo- morphine has the desired
analgesic activity.
Poppy plant; papever sommniferum
O
OH
HO
(3R,4S,8S,9R) - anti-malarial
(-)-quinine
OH
H
O
N

4. Valliappan Kannappan
Valliappan Kannappan
Proteins
H
H
O
M
O
C
H
I
R
A
L
I
T
Y
S
DNA, RNA
Sugars Amino Acids
D
D-
- L
L-
-
Look @ Molecules of Life
@ Molecules of Life
most of the Biological macromolecules: Chiral
Importance of Chirality 2021
S
I
G
N
A
T
U
R
E
O
F
L
I
F
E
 Enzymes
 Receptors
 Carbohydrates
 Nucleic acids
 Transmitters
 Hormones

5. Valliappan Kannappan
Valliappan Kannappan
N
E
W
M
O
L
E
N
T
I
T
e-mcc
47%
e-scc
18%
rac-
5%
Major proportion of medicines are chiral
Chiral drugs
Importance of Chirality 2021
T
I
E
S
ach
28%
m-dia
2%
67% chiral
67% chiral
http:// www. fda.gov/cder/rdmt/
Approved Jan 2004 to June 2006
Approved Jan 2004 to June 2006

6. Valliappan Kannappan
Valliappan Kannappan
Biological targets are chiral and so are the
molecules (drugs) that interact with them
Importance of Chirality 2021
molecules (drugs) that interact with them
Source: Christopher Welch, Chiral India, 2016.
Hence, mirror-image perspective is important when the
molecule under study is chiral.

7. Valliappan Kannappan
Valliappan Kannappan
Regulatory Environment
Regulatory Environment
Importance of Chirality 2021

8. Valliappan Kannappan
Valliappan Kannappan
Enantiopure Drugs employed in drug therapy (select)
Enantiopure
Enantiopure drug
drug Therapeutic indication
Therapeutic indication Therapeutic area
Therapeutic area
S-amlodipine Antianginal / Antihypertensive
Cardiology
S-metoprolol Antihypertensive
S-atenolol Antihypertensive
Esomeprazole Proton pump inhibitor
U
N
I
C
H
I
R
A
L
D
R
Importance of Chirality 2021
Gastroenterology
S-pantoprazole Proton pump inhibitor
Dexrabiprazole Proton pump inhibitor
Levosalbutamol Bronchodilator
Pulmonology
Levocetrizine Antihistaminic
R-formetrol Antihistaminic
Levofloxacin Antibacterial Infectious diseases
R
U
G
S

9. Valliappan Kannappan
Valliappan Kannappan
Enantiopure
Enantiopure drug
drug Therapeutic indication Therapeutic area
Therapeutic area
S-penicillamine Rheumatoid Arthritis
Rheumatology /
Pain/ Inflammation
S-etodolac NSAID
Dexketoprofen; (S-) NSAID
Dexibuprofen; (S-) NSAID
S-ketamine Anesthetic
U
N
I
C
H
I
R
A
L
D
R
Enantiopure Drugs employed in drug therapy (select)
Importance of Chirality 2021
S-ketamine Anesthetic
Anesthesiology
Levobupivacaine Local anesthetic
Ropivacaine Local anesthetic
Cisatracurium Skeletal muscle relaxant
Levothyroxine Anti-hypothyroidism Endocrinology
Levodopa Anti-Parkinson Neuropsychiatry
R
U
G
S

10. Valliappan Kannappan
Valliappan Kannappan
 Stereochemistry is a key characteristic of life
science, and chirality is often crucial for specific BA.
 Appeal to academia to provide more space for chirality
in their deliberations on life science research/teaching
and also try to mitigate the so called “stereophobia”
Concluding Remarks
Concluding Remarks
Importance of Chirality 2021
and also try to mitigate the so called “stereophobia”
that exist both among faculty and students (debatable !!!).
 Call upon teachers to empower the student community
with chiral science, which is an integral part of drug
discovery and development process.

11. Valliappan Kannappan
Valliappan Kannappan
Thanks for you time
Thanks for you time
Importance of Chirality 2021
valliappan
valliappan
Chirally Yours
Chirally Yours