PCTE college of Technical Education

FACULTY OF PHARMACEUTICAL SCIENCE

COURSE – B.PHARMA
SEMESTER – 6th
SUBJECT– MEDICINAL CHEMISTRY (BP 601-T)
P RE SENTATION S YNOPSIS

TOPIC: DEVELOPMENETS IN SULPHONAMIDE DERIVATIVES

NAME: THAKUR PRAVA JYOTI
UNIV.ROLL.NO: 1817795
OFFICIAL E-MAIL ADDRESS: pravajyoti900@gmail.com
TABLE OF CONTENTS:
Introduction
Developments in sulfonamides derivatives
Anti-cancer Activities of Coumarin Sulfonamide Derivatives
Anti-oxidant activities of coumarin sulfonamides derivatives
Anti-inflammatory activities of coumarin sulfonamide derivatives
Anti-fungal activities of coumarin sulfonamide derivatives
Conclusion
Reference

BRIEF INTRODUCTION OF TOPIC:-

Sulfonamides are privileged and pivotal templates which have a broad spectrum of
applications in the fields of medicine, pharmacology and pharmaceutics. It gives
biomedical activities such as anti-bacterial, antiviral, antifungal, anti-inflammatory
and anti-cancer.
Sulfonamide molecular structure is similar to p-Amino benzoic acid (PABA) which
is needed in bacteria organisms as a substrate of the enzyme dihydro pteroate
synthetase for the synthesis of Tetra Hydro Folic acid (THF).
 Folic acid - synthesized from PABA, pteridine and glutamate.
 All sulfonamides are analogs of PABA. All sulfa drugs are bacteriostatic.

Mechanism of Sulfonamide:
 SAR of Sulfonamide :

 The amino & Sulphonyl groups on the benzene ring are essential & should be
in 1,4-position Replacement of Aromatic ring by other ring systems or the
introduction of additional substituents on it decreases or abolish activity.
 Exchange of the -SO2NH group by –CO-NH reduce the activity.
 Substitution of Aromatic Heterocyclic nuclei at N1 - yields highly potent
compounds.
 N1 –Di substitution in general leads to inactive. SAR of Sulfonamide

DEVELOPMENETS IN SULPHONAMIDE DERIVATIVES

The Coumarin sulfonamide moiety can be termed as a ‘Master Key’ as it is an

important and privileged structural motif which is an integral part of diversified
hybrid structural libraries of compounds targeted to elicit varied pharmacological
activities. The pharmacological profile of coumarin sulfonamide can be categorized
into the following classes:
 Anti-cancer activities
 Anti-oxidant activities
 Alkaline phosphatase inhibitory effects
 Anti-inflammatory activities
 Anti-bacterial activities
 Antifungal activities
 Anti-cancer Activities of Coumarin Sulfonamide Derivatives :

Pyrimidine based coumarinyl sulfonamide scaffolds 21

Sulfonamide derivatives - These synthesized scaffolds were screened against B16-

F10 (mouse melanoma) and MCF-7 (breast carcinoma) cell lines. The substituted
pyrimidine based coumarin benzene sulfonamide analogue (21) was the best
inhibitor against carbonic anhydrases, such as cytosolic off-target isoform (hCAs-
II), with an IC50 value of 0.063 μM as compared to the reference drug AZA
(Acetazolamide) which had an IC50 value of 0.016 μM and SA (sulfanilamide)
with an IC50 value of 0.26 μM. Scaffold (21) showed the best anti-cancer activity
against the trans membrane tumor-associated isoform (hCAs-IX) with an IC50
value of 0.024 μM when compared with AZA and SA (IC50 values of 0.028 and
0.29 μM respectively).

Thiazole based coumarin analogue 23 which displayed anti-cancer activity

The thiazole based coumarin naphthalene sulfonamide scaffold (23) showed the
strongest inhibition against hCA I with an IC50 value of 5.63 μM. Derivative (23)
also demonstrated remarkable inhibition against hCA II with an IC50 value of 8.48
μM.
 Anti-oxidant activities of coumarin sulfonamides derivatives

Substituted coumaryl thiazole derivatives

Substituted coumaryl thiazole derivatives and evaluated their antioxidant activities

using the radical scavenging 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid
(ABTS) assay and cupric reducing antioxidant capacity (CUPRAC) assay. The
methoxy substituted thiazole based benzene sulfonamide scaffold (35)
demonstrated ABTS anti-oxidant activity with an IC50 value of 48.83 ± 1.38 μM as
compared to the standard reference drug quercetin which had an IC50 value of
15.49 ± 2.33 μM. Scaffold (35) showed excellent antioxidant cupric reduction
capabilities with an A0.50 value of 23.29 ± 0.02 μM while the reference quercetin
had an A0.50 value of 18.47±0.04 μM

Sulfamoylphenyl acetamide based 4-methyl coumarin derivative

The antioxidant activity of the sulfamoylphenyl acetamide based 4-methyl

coumarin derivative (36) was determined by the 1,1-diphenyl-2-picrylhydrazyl
(DPPH) scavenging method and ferric reducing antioxidant power (FRAP) assay.
The hybrid structure (36) demonstrated the best DPPH activity with an IC50 value
of 0.66 ± 0.01 mM as compared to quercetin which had an IC50 value of 8.12 ±
0.13 mM. Scaffold (36) exhibited the best antioxidant potential using DPPH as
opposed to FRAP. The SAR studies revealed that derivative (36) showed good
antioxidant potential due to substitution of a methyl group on position 4 of the
coumarin ring.

Anti-inflammatory activities of coumarin sulfonamide derivatives

Chlorophenyl substituted pyrazol based coumarin benzene sulfonamide

Synthesized a novel and biologically active series of eighteen coumarinyl thiazole

carrying benzene sulfonamide derivatives. These scaffolds were investigated for
their in vitro antimicrobial activity and in vivo anti-inflammatory activity. The
chlorophenyl substituted pyrazol based coumarin benzene sulfonamide scaffold
(41) had the most powerful anti-inflammatory activity against cyclooxygenase
(COX-1 and COX-2) when compared to the standard drug indomethacin.

Pyrazole Moiety containing coumarin sulfonamide

Reported on synthetic strategies to afford pyrazole moiety containing coumarin
sulfonamide structures and evaluated their anti-proliferation activity in vitro.
Scaffold (42) was highly biologically active against COX-2 with an IC50 value of
0.23 ± 0.16 μM when compared to the reference drug celecoxib which had an IC50
value of 0.41 ± 0.28 μM. Scaffold (42) exhibited inhibitory activity against 5-LOX
with an IC50 value of 0.87 ± 0.07 μM, in comparison with the reference standard
zileuton which had an IC50 value of 1.35 ± 0.24 μM. Derivative (42) demonstrated
the most potent activity (4.48 ± 0.57 μM) against A549 (human lung cell line) as
compared to celecoxib which had an IC50 value of 7.68 ± 0.55 μM.

Anti-bacterial activities of coumarin sulfonamide derivatives

Coumarin-6-sulfonamide

Reported the synthesis of coumarin-6-sulfonamide compounds and tested their

anti-bacterial potential in vitro against ATCC35218 (Escherichia coli) and
ATCC6538 (Staphylococcus aureus). The thiazole based coumarin sulfonamide
scaffold (44) demonstrated remarkably high anti-bacterial activity against S.
aureus (ATCC6538) with a zone of inhibition (ZI) value of 24 mm as compared
to the reference drugs ampicillin and chloramphenicol which had ZI values of
28 mm and 19 mm, respectively. Scaffold (44) also exhibited strong anti-
bacterial activity against E. coli (ATCC35218) with a ZI value of 16 mm as
compared to ampicillin and chloramphenicol which had ZI values of 15 and 22
mm, respectively

Pyrazole moiety containing coumarin sulfonamide

Reported on synthetic strategies to afford pyrazole moiety containing coumarin

sulfonamide structures and evaluated their anti-proliferation activity in vitro.
Scaffold (42) was highly biologically active against COX-2 with an IC50 value
of 0.23 ± 0.16 μM when compared to the reference drug celecoxib which had an
IC50 value of 0.41 ± 0.28 μM. Scaffold (42) exhibited inhibitory activity
against 5-LOX with an IC50 value of 0.87 ± 0.07 μM, in comparison with the
reference standard zileuton which had an IC50 value of 1.35 ± 0.24 μM.
Derivative (42) demonstrated the most potent activity (4.48 ± 0.57 μM) against
A549 (human lung cell line) as compared to celecoxib which had an IC50 value
of 7.68 ± 0.55 μM.

Antifungal activities of coumarin sulfonamide derivatives

4-hydroxycoumarin sulfonamides

Evaluated 4-hydroxycoumarin sulfonamides hybrids for their antifungal activity

in-vitro against A. flavus, T. longifusus, C. glaberata, M. canis, F. solani and C.
albicans fungal strains. The amino substituted coumarin benzene sulfonamide
scaffold (48) showed significant activity against M. canis with an MIC value of
74 μg/mL in comparison to the reference drug miconazole (MIC = 98.4 μg/mL).
The amino substituted pyrimidinyl based coumarin sulfonamide derivative (49)
exhibited significant activity against M. canis with an MIC value of 86 μg/ mL
in comparison with miconazole (MIC = 98.4 μg/mL).

Amino isoxazolyl coumarin benzene sulfonamide

The substituted amino isoxazolyl coumarin benzene sulfonamide (50) showed

remarkably high activity against F. solani with a MIC value of 69 μg/mL as
compared to miconazole (MIC = 73.25 μg/mL). Compound (49) also demonstrated
excellent anti-fungal activity against F. solani with a MIC value of 82 μg/mL which
was greater than the reference standard drug miconazole which had a MIC value of
73.25 μg/mL.
CONCLUSION:
As the pharmaceutical is one of the fast growing and there is a lot of recent
advancement occurs in the field of theses growing industry which become more
helping to making provide a great support system by which the therapeutically
activity of various medicinal drugs and various class of drug is increase and also
they making working of various pharmaceutical preparation more efficient.
Sulfonamides are the class of drugs which deals a broad spectrum of activities such
as anti-bacterial, antiviral, antifungal, anti-inflammatory and anti-cancer.
So, there is a lot of different advancement occurs in the activity of sulfonamide by
changing their chemical composition making them more efficient towards there
activity.

REFERENCE:
 Author : Alan Bole

https://pubs.acs.org/doi/10.1021/acsomega.0c00280 (DATE : 06-05-2021)

 Author : Andy Norris

https://www.nature.com/articles/s41598-019-43083-z ( DATE : 07- 05 -2021 )

 Author : Ruth Jessen Hickman , MD

https://www.degruyter.com/document/doi/10.1515/hc-2020-0008/html

( DATE : 07- 05 -2021 )

FULL URL OF RESOURCES/AUTHENTIC REFERENCES USED FOR
RESEARCH:
 Author : Dr. Nitin jayan

https://listz.in/top-10-diagnostic-companies-pathology-labs-in-

india.html#:~:text=%231%20DR%20LAL%20PATHLABS,diagnostic%20services

%20in%20various%20domains. DATE : (06-05-2021)

  Author : Alan Bole

https://www.trendrr.net/1863/best-diagnostic-companies-pathology-labs-india-

famous-laboratories-10-top-list/ DATE : (06-05-2021)

 Author : Andy Norris

https://tigerfeathers.substack.com/p/the-business-of-diagnostics-and-the ( DATE :

07- 05 -2021 )

 Author : Ruth Jessen Hickman , MD

https://nathealthindia.org/pdf/Diagnostic%20report.pdf ( DATE : 07- 05 -2021 )