A simple and efficient protocol for the synthesis of pyrazolines: Molecular docking and

biological studies
Siddram Nadigar M.S.a, Dileep D.N.a, Rekha N.D.b, Rohith Ga, Suhas Ra*
aPostgraduate Department of Chemistry, JSS College of Arts, Commerce and Science, Ooty Road, Mysuru-25
bPostgraduate Department of Biotechnology, JSS College of Arts, Commerce and Science, Ooty Road, Mysuru-25

Presentation by
SIDDARAM NADIGAR M.S.
Research Scholar
J.S.S. College, Ooty Road, Mysuru-25

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 Biological applications Other applications

Anticancer Antimicrobial

Anti-
Antioxidant inflammatory

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 Drugs containing pyrazolines
Sl. No. DRUG STRUCTURE APPLICATIONS
NAME
1 Ibipinabant Selective cannabinoid
CB1 receptor inverse
agonist

2 YC-1 Anticancer

3 E-6087 Non-steroidal anti-

inflammatory drug for
the treatment of
osteoarthritis and pain
4 SLV-330 CNS disorder

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 Problems associated with the existing synthetic protocols

➢ Flammable solvents
➢ More reaction time
➢ Non-ecofriendly
➢ Harsh bases

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BASES REMARKS SOLVENTS REMARKS TIME REMARKS
NaOH 1h incomplete, 2h Ethanol Impurity
30 min Partial reaction
good reaction; DCM Impurity
Emulsion during 1h Complete & clear
workup H2O No reaction
reaction
Na2CO3 Incomplete reaction THF Impurity
2h Complete reaction
ACN Very good reaction,
KOH Impurity, Incomplete
Impurity 4h Complete reaction
rection
Toluene Impurity (impurity)
Pyridine 1h, good reaction
DMSO Very good product (1h) 8h Impurity formation
TEA 3h, good reaction
Triethanol Incomplete reaction TEMPERATURE REMARKS
12h Impurity formation
amine 0 0C No reaction
24h More impurities
K2CO3 Very good reaction Rt No reaction
(1h) 5
Reflux 1h
Synthetic Scheme

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 Interactions and docking score
Entry R R1 R2 Score H-bonding van der Waals Pi- Pi-sigma Pi-alkyl
Kcal/mol anion
2a H Ph CH3 -5.8 Arg-A:452 Trp-A:576, Pro-A:575, Gly- Asp- Ala-A;455 Ala-A;572
A:451, Gly-A:573, Ile-A:425, A:568
Ala-A:573, Phe-A:449,Thr-
A:566,Thr-A:450

2b 2-OH, Ph CH3 -6.0 Gly-A:451, Trp- Gly-A:426, Arg-A:452, Ala- Asp- _ Ala-A:572
A:576, Lys-A:435 A:572,A:573, Thr-A:450, Ile- A:568
5-NO2 A:592

2c 4-OH CH3 CH3 -5.1 Trp-A:576 Thr-450, Asp-568, Gly- _ _ Ala-455,572, Pro-575, Arg-
574,451,576, Ile-425 452

2d 4-Cl C6H10 C6H10 -4.9 Ile-A:425 Gly-A:426,A:451, Ala-A:572,573, Asp- His-A:569 Ala-A:455,A:572, Pro-A:575
Thr-A:450, Trp-A:576, Ile-592 A:568

2e 2,3- C6H10 C6H10 -6.3 Thr-A:450 Gly-A:593, Thr-A:450, Lys- _ _ Ala-A:455, Phe-A:449, Arg-
A:564, Ala-A:573,A:455, Pro- A:452
OMe A:575, Ile-A:425

2f 3,4- COCH3 CH3 -5.4 Ile-A:425 Gly-A:451, Ala-A:573, Thr- _ _ Ala-A;572, His-A:569, Pro-
A:450, Arg-A:447 A:575, Phe-A:449, Trp-
OMe A:576

2g 2,3- COCH3 CH3 -4.7 Ala-A:573 Gly-A:451,426,574, Pro-A:575, Asp- Ala- _

Thr-A:450, Arg-A:452, Ile-A:425 A:568 A:572,465,
OMe His-A:569

2h 4-OH Ph CH3 -6.3 Thr-A:450 Gly-A:574,451,593, Trp-A:576, Asp- _ Ala-A:572,575, Pro-A:575

Ala-A:573, Arg-A:452, Thr- A:568
A:450, Ile-A:425

2i 3,4- C6H10 C6H10 -5.6 Arg-A:452 Ala-A:572, Gly-A:451,574,426, _ _ Arg-A:452, Phe-A:449, Ala-
Pro-A:572575, Asp-A:568, Arg- A:455
OMe A:447, Thr-A:566, Lys-A:564,
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Ile-A:425
 PROTEIN : ACONITASE
Molecular docking studies
PROTEIN ID : 1AMJ

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Inhibition studies of the aconitase enzyme

Entry Amount of citric acid

produced in g/L
2a 2.56
2b 4.87
2c 4.48
2d 16.14
2e 15.63
2f 13.58
2g 4.35
2h 3.1
2i 2.9

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 Entry % of
inhibition
2a 85.45
2b 93
2c 71.46
2d 75.61
2e 93.71
2f 85.71
2g 57.2
2h 51.14
2i 64.56

Inhibition of F. oxysporum by Trichoderma in Percent inhibition of

the presence of pyrazoline derivatives F. Oxysporum by
Trichoderma in the
presence of various
Pyrazoline
derivatives.
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 3.5
3.5

Growth of Rhizobium in fold activity

Growth of phosphate solublizing
3 2a 2a
3

bacteria in fold activity

2b 2b
2.5 2.5
2c 2c
2 2
2d 2d
1.5 1.5
2e 2e
1 2f 1 2f
0.5 2g 0.5 2g
2h 2h
0 0
0.5 2.5 4.5 6.5 2i 1 2 3 4 5 2i
Concentration in µg Concentration in µg

Effect of pyrazoline derivatives on the growth of

phosphate solubilizing bacteria Effect of pyrazoline derivatives on the growth
of Rhizobium
1.6
Growth of Pseudomonas fluorescence
1.5 2a
1.4 2b
2c
in fold activity

1.3
1.2 2d

1.1 2e
2f
1
2g
0.9
2h
0.8
1 2 3 4 5 2i
Concentration in µg

Effect of pyrazoline derivatives on the

growth of Pseudomonas fluorescence 11
Thank you

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