Insilico design and docking of Novel chemical compounds

Presented By
S.SHAH FAISAL 12T01R0050
T.NAGAIAH 12Y01R0051
P.SIREESHA 12Y01R0073
S.AYESHA SULTANA 12Y01R0077
S.ANWAR HUSSAIN 13Y05R0011
INSILICO DESIGN, SYNTHESIS,
CHARACTERIZATION AND BIOLOGICAL
EVALUATION OF SOME NOVEL 1-
HYDROXYNAPHTHALEN-2-YL DERIVATIVES
UNDER THE SUPERVISION OF
Mr. T. RAJ KUMAR, M.Pharm
Associate Professor,
Dept. of Pharmaceutical Chemistry,
CES College of Pharmacy,
Kurnool.

CONTENTS
 Introduction
 Review of literature
 Objectives of study
 Plan of the work
 Experimental work
 Biological Activity
 Anti-Microbial Activity
 Anti-Inflammatory Activity
 Results& Discussion
 Summary and Conclusion
 Future scope
 References

Chalcone is an aromatic ketone and an enone that forms the central core for a
variety of important biological compounds, which are known collectively as
chalcones or chalconoids. Benzylideneacetophenone is the parent member of
the chalcone series. The alternative name given to chalcone are phenyl styryl
ketone, benzalacetophenone, β-phenylacrylophenone, ɣ-oxo-α, ɣ-diphenyl-α-
propylene and α-phenyl-β-benzoylethylene.
Chalcones and their derivatives demonstrate wide range of biological activities
such as anti-diabetic, anti-neoplastic, anti-hypertensive, anti-retroviral, anti-
inflammatory, anti-parasitic, anti-histaminic, anti-malarial, anti-oxidant, anti-
fungal, anti-obesity, anti-platelet, anti-tubercular, immunosuppressant, anti-
arrhythmic, hypnotic, anti-gout, anxiolytic, anti-spasmodic, anti-nociceptive,
hypolipidemic, anti-filarial, anti-angiogenic, anti-protozoal, anti-bacterial, anti-
steroidal, cardioprotective, etc .[1]
INTRODUCTION

SYNTHESIS
Chalcones can be prepared by an aldol condensation between
benzaldehyde and acetophenone in the presence of sodium hydroxide as a
catalyst.
Mechanism

REVIEW OF LITREATURE
Bhagat et al. (2006), Used Commercially available LiOH·H2O as a highly
efficient dual catalyst for Claisen-Schmidt condensation of various aryl methyl
ketones with aryl/hetero aryl aldehydes by providing an easy synthesis of 1,3-
diaryl-2-propenones under mild conditions.
Biswajit Chandra Das et al synthesized substituted chalcone derivatives and
evaluated Anthelmintic and Anti-microbial activities.
Rajendra Prasad Y et al (2006) synthesized Five novel chalcones by
condensing 2-hydroxy-1-acetonaphthone with aldehyde derivatives in dilute
ethanolic potassium hydroxide solution at room temperature.
M. R. Jayapal and N. Y. Sreedhar (1997) proposed:-
Novel method for the synthesis of 2,6‐dihydroxy substituted chalcones via aldol co
ndensation. in the presence of SOCl2 / EtOH as a catalyst.
Yogesh S et al.(1978) synthesized twelve new chalcones by Claisen-Schmidt
condensation and studied for their insect antifeedant activity against the mealy bug
of cotton (Phenacoccus solanopsis). All the chalcones have exhibited significant
activity.

Venkatesan J et al (2007) Synthesised and evaluated biological activities of 4, 6-
diaryl substituted-4,5-dihydro-2-amino pyrimidines
Vibhute Y et al (2011) reported an efficient and operationally simple reaction is shown
between substituted 2-acetyl-1-naphthol/2-acetyl-1-naphthol and different substituted
benzaldehydes in presence of base afford chalcones in quantitative yield using
grindstone technique.
Alka NC et al (2011) made a wide search program towards new and efficient
antimicrobial agents; substituted chalcones have been synthesized by condensing
benzaldehyde derivatives with acetophenone derivatives in dilute ethanolic sodium
hydroxide solution at room temperature.
Rahman MA (2011) presented the review highlights of the recently synthesized
chalcones and their derivatives possessing important pharmacological activities.
Chetana B. Patil (2009) highlighted antioxidant potential of chalcone, mechanism of
antioxidant activity of chalcones and structure activity relationship of chalcone
derivatives for antioxidant ability and different methods to evaluate antioxidant activity
of chalcone, anti-inflammatory, cytotoxic and anti-hyperglycemic activity of chalcones is
also discussed in this review article.
Rajitha G (2015) synthesized a series of N-(naphthalene-2-yl)-3-(substituted phenyl)
prop-2-enamides were synthesized by reaction of β –acetyl amino naphthalene with
substituted aromatic aldehydes in presence of absolute ethanol and 30% NaOH.

Bhandarkar SE et al (2014) 2-acetyl-1-naphthol 2 is prepared by Modified
Nenchi’s method which on treatment with furfuraldehyde and KOH gives 1-(1-
hydroxy naphthalen-2-yl)-3-(furan-2-yl) prop-2-ene-1-ones 3 in excellent yield.
Siva sanker reddy L et al (2015) In pursuit of compounds which show
antimicrobial activity, synthesis of novel morpholine linked substituted chalcones
done by condensing different aldehydes with diazotized 4-amino acetophenone
coupled to morpholine and evaluated them for in-vitro anticancer, anti-inflammatory
and antibacterial activities.
Siva sanker reddy L et al (2016) In search of molecules that possess biological
activity, synthesis of novel pyrrolidines chalcones (AP-JP) obtained by condensing
different aldehydes with diazotized 4-amino acetophenone coupled to pyrrolidine
and evaluate them for in vitro anticancer, anti-inflammatory and antibacterial
activities was undertaken.
Siva sanker reddy L et al (2016) , synthesized pyrazolines and chalcones were
screened for anticancer activity against human breast cancer cell lines-MCF-7 and
MDAMB-468 in the range of 100 nm to 100 µm. Inhibition of bovine albumin
denaturation and heat-induced hemolysis in vitro methods were followed to
screen for anti-inflammatory activity.

OBJECTIVES OF STUDY
In an effort to continually develop potent anti-inflammatory
agents, novel series of napthalene chalcones were synthesized
and their inhibitory effects on the bovine albumin and Heat
induced hemolysis were evaluated in-vitro.
It was thought worthwhile to design few
Synthesis of 1-(1-hydroxynaphthalen-2-yl) ethanone from
α-napthol.
To synthesize 1-hydroxynapthalen-2-yl derivatives by
reacting 1-(1-hydroxynapthalen-2-yl) ethanone with
substituted benzaldehydes.
The chalcones were prepared by Claisen-Schmidt condensation
(Scheme I)

PLAN OF WORK
The work plan is divided into 4 parts.
1. To synthesize 1-(1-hydroxynaphthalen-2-yl) ethanone
from α-napthol.
2. To synthesize 1-hydroxynaphthalen-2-yl derivatives by
reacting with 1-(1-hydroxynaphthalen-2-yl) ethanone with
substituted benzaldehydes
3. To characterize derivatives using NMR, Mass and IR
spectrometry.
4. To evaluate the Anti-inflammatory and Anti-bacterial
activity.

EXPERIMENTAL WORK
INTERNET BASED IN-SILICO DESIGN
TOOLS AND MATERIALS USED
In our present study we used the biological databases like Protein Data Bank (PDB)
and soft ware’s like ACD Chem Sketch. ACD/Chem Sketch is the powerful all-
purpose chemical drawing and graphics package from ACD/Labs developed to help
Chemists quickly and easily draw molecules, reactions and schematic diagrams,
calculate chemical properties and design professional reports and presentations.
ACD Chem Sketch can convert SMILES notations to Structure and also can convert
ACD Chem Sketch Structure to SMILES. [19]
The Protein Data Bank (PDB) is the single worldwide archive of structural data of
biological macromolecules established in Brookhaven National Laboratories (BNL)
in 1971.

pkCSM predicting small-molecule pharmacokinetic properties using
graph-based signatures
The pkCSM signatures were successfully used across five main different
pharmacokinetic properties classes to develop predictive regression and
classification models.
DOCKING BY HEX8.0
Hex is an interactive molecular graphics program for calculating and
displaying feasible docking modes of pairs of protein and DNA molecules.
Hex can also calculate protein-ligand docking, assuming the ligand is rigid,
and it can superpose pairs of molecules using only knowledge of their 3D
shapes. Hex has been available for about 12 years now, but as far as I know,
it is still the only docking and superpostion program to use spherical polar
Fourier (SPF) correlations to accelerate the calculations, and it’s still one of
the few docking programs which has built-in graphics to view the results.
Also, as far as I know, it is the first protein docking program to be able to use
modern graphics processor units (GPUs) to accelerate the calculations

Procedure for Docking Studies using HEX:
The parameters used in HEX for the docking process were;
Correlation type – Shape only
FFT Mode – 3D fast lite
Grid Dimension – 0.6
Receptor range – 180 Ligand Range – 180
Twist range – 360 Distance Range – 40.

Targets
Table 1: Structure of targets
1IS2 1W07 3COX
4COX 6C0X
Ligands The structures were drawn in ACD Labs and then converted to PDB
format using Open Babel GUI 2.2.1 and further used for docking studies.

Table 2: CHEMICALS AND SOLVENTS
S.NO NAME OF CHEMICALS NAME OF SUPPLIER
1 2-Chloro Benzaldehydes S.D.Fine Chemicals(India)
2 4-Nitro Benzaldehydes S.D.Fine Chemicals(India)
3 2,3-DiMethoxy Benzaldehydes S.D.Fine Chemicals(India)
4 3,4-DiMethoxy Benzaldehydes S.D.Fine Chemicals(India)
5 3,4,5-TriMethoxy Benzaldehydes S.D.Fine Chemicals(India)
6 Vanillin S.D.Fine Chemicals(India)
7 DMSO S.D.Fine Chemicals(India)
8 Ethanol S.D.Fine Chemicals(India)
9 Potassium hydroxide S.D.Fine Chemicals(India)
10 α-napthol S.D.Fine Chemicals(India)
11 Acetic acid S.D.Fine Chemicals(India)
12 Zinc chloride S.D.Fine Chemicals(India)

Table 3: INSTRUMENTS USED
S.NO EQUIPMENTS MAKER
1 NMR Spectrophotometer BRUKER 400MHZ
2 Mass Spectrophotometer
3 UV Spectrophotometer UV Pharma Spec. 1700 (SHIMADZU)
4 Hot air Oven Vision Lab Equipments
5 Magnetic stirrer Vision Lab Equipments
6 Vacuum pump Vision Lab Equipments
7 Precision weighing Balance Contech (0.1 mg precison)
8 Precision Melting point Apparatus Vision Lab Equipments
9 IR Spectrophotometer BRUKER
10 UV Chamber Vision Lab Equipments

EXPERIMENTAL SECTION
Step I: Synthesis of 1-(1-hydroxynaphthalen-2-yl)ethanone from α-napthol
In hot glacial acetic acid (80ml), fused ZnCl2(50 gm) was added and refluxed till
dissolved, then powdered 1-naphthol (30gm )was added and the mixture was refluxed
for about 8 hours then cooled & poured in acidulated water. The solid obtained was
filtered, washed, dried and recrystallized from rectified spirit to obtain compound 2.
OH
GAA CH3
OOH
α- NAPTHOL 1-(1-hydroxynaphthalen-2-yl)ethanone

Step II: Synthesis of Chalcones
To a 20 ml solution of 20% Potassium hydroxide in distilled water, acetophenone
(0.001 mol) was added and dissolved. To this benzaldehyde (0.001 mol) was added
in small amounts with continuous stirring with the help of a mechanical stirrer or
about 2 h. The mixture was left in refrigerator for 24 h. Then the yellowish product
thus formed is filtered, dried and recrystallized from ethanol. The synthesized
compounds were monitored by TLC. Physical data of the compound is given in
table 4
CH3
OOH
O
R
+
1-(1-hydroxynaphthalen-2-yl) ethanone Substituted
aromatic aldehyde
OH
O
R
KoH

List of Synthesized molecules
Code Structure IUPAC Name
A (2E)-1-(1-hydroxynaphthalen-2-yl)-3-(4-
nitrophenyl)prop-2-en-1-one
B (2E)-3-(4-chlorophenyl)-1-(1-
hydroxynaphthalen-2-yl)prop-2-en-1-one
C (2E)-3-(4-hydroxy-3-methoxyphenyl)-1-
(1-hydroxynaphthalen-2-yl)prop-2-en-1-
one
D (2E)-1-(1-hydroxynaphthalen-2-yl)-3-
(3,4,5-trimethoxyphenyl)prop-2-en-1-one
E (2E)-3-(3,4-dimethoxyphenyl)-1-(1-
hydroxynaphthalen-2-yl)prop-2-en-1-one
OH
O
N
+
O
-
O
OH
O
Cl
OH
O
O CH3
OH
OH O
O
CH3
O
CH3
O
CH3
OH
O O
CH3
O
CH3
Table no :-4

Table 5:List of Synthesized molecules
S.No SMILE Notation
A [O-][N+](=O)c1ccc(cc1)/C=C/C(=O)c3ccc2ccccc2c3O
B Clc3ccc(/C=C/C(=O)c2ccc1ccccc1c2O)cc3
C Oc1ccc(cc1OC)/C=C/C(=O)c3ccc2ccccc2c3O
D COc1c(cc(cc1OC)/C=C/C(=O)c3ccc2ccccc2c3O)OC
E COc1cc(ccc1OC)/C=C/C(=O)c3ccc2ccccc2c3O
Table 6: Type of Chalcones Substitutions
Product R1 R2
A 4-NO2
B 4-Cl
C 4-OCH3 3-OH
D 3-OCH3 4-OCH3, , 5-OCH3
E 3-OCH3 4-OCH3

ANTIBACTERIAL STUDIES
All the extracts were evaluated for antimicrobial activity using 2-fold serial
broth dilution method in duplicates. This method depends upon the inhibition
of growth of a microbial culture in a uniform solution of antibiotic in a liquid
medium that is favourable to its rapid growth in the absence of the antibiotic.
Minimum Inhibitory Concentration (MIC) of the all extracts was determined.
The MIC is the lowest concentration of tested compounds that completely
inhibited the growth of the test organisms after 24 and 48 h of incubation at
37 °C and 27 °C for bacteria and fungi, respectively.
Table 7: Solubility of drugs in DMSO and water for antimicrobial studies
S.No Compound Soluble
1. Compound A-E 100% Sterile DMSO, Distilled
Water,Ethanol.

Instruments:
Incubator
Hot air oven
PH Meter (324)
Refrigerator
Laminar flow
Autoclave
Ultra low temperature cabinet
Chemicals
Malt extract powder for bacteriology
Glucose crystalline Pure
Peptone type-1 used as a culture media ingredients
Agar powder for bacteriology
Hydrochloric acid (0.1N),
Sodium Hydroxide (0.1N)
Dimethyl sulfoxide (DMSO)
All the appropriately weighed quantities of ingredients were dissolved in the
specified quantity of distilled water. The pH was adjusted to 7.2 – 7.4 and was
sterilized in autoclave at 15 lbs pressure and 121° C for 20 minutes.

Material and methods:
Trimethoprim was used as standard drug for the comparison of antibacterial
activity. Stock solutions of each 5 ml were prepared in sterile DMSO
(Dimethyl sulfoxide) at a concentration of 4mg/ml.
The following ingredients were used for preparation of media.
Table 8 :Nutrient Broth media.
INGRIDIENTS (Single Strength) (Double Strength)
Beef extract 1.0 g 2.0 g
Yeast extract 2.0 g 4.0 g
Peptone 5.0 g 10.0 g
Sodium Chloride 5.0 g 10.0 g
Distilled water 1.0 L 1.0 L
pH 7.2 – 7.4 7.2-7.4
All the appropriately weighed quantities of ingredients were dissolved in
the specified quantity of distilled water. The pH was adjusted to 7.2 – 7.4
and was sterilized in autoclave at 15 lbs pressure and 121° C for 20
minutes.
:

Table 9: Details of bacterial strains used for determination of antibacterial
activity
Name Escherichia coli
NCIM 2810
Bacillus substills
MTCC441
Growth Medium Nutrient broth
medium
Nutrient broth medium
Growth Condition Aerobic 30 Days
Incubation
Temperature
37oC 37oC
Incubation Time 24 Hours 24 Hours
Subculture 30 Days 30 Days

Preparation of Inoculum
The suspension of the organisms obtained after revival and it was used for
streaking over nutrient agar plates and subjected to incubation at 30 °C for 7
days.
From the cultures obtained from the streaking in Petri dishes culturing and sub
culturing was performed until pure isolated colonies were obtained.
From these isolated colonies fresh sterile nutrient broth media were re
inoculated and all the test tubes were incubated at 30° C for 7 days.
These nutrient broth cultures served as inocula for the determination of
antimicrobial activity of the compounds.
Cup-plate/Cylinder- plate method
Stock solutions of all compounds Compound A-E were prepared in the
concentrations of 5mg/ml with sterile DMSO and measured quantities of
stock solutions were diluted to prepare conc. of 1000, 500, 250, 125, 62.5
and 31.25 µg / ml of the extract.
Forty eight hours cultures of required strains were maintained.
Half ml (for 100 ml of media) of 48 hrs culture of was inoculated into the
nutrient agar media at 40-50 0C.

Inoculated media (30 ml) was poured in to the Petri plates up to 4-5 mm
thickness and allowed to solidify.
Cylinders/cups were prepared by using sterile cork borer of 5 mm internal
diameter.
About 0.1ml of the different concentrations of the extract was added
to the cups. The well on Petri plates were loaded with solvent (100% sterile
DMSO, 15% sterile DMSO and sterile water).
The samples were allowed to diffuse uniformly, by keeping it in
refrigerator for 1 hour.
The Petri plates were incubated for 48 hours at 30oC and the zone
of inhibition was measured.

INVITRO ANTI INLAMMATORY ACTIVITY
Assessment of invitro anti-inflammatory activity
Inhibition of albumin denaturation
The anti-inflammatory activity was studied by using inhibition of
albumin denaturation technique which was studied according to
Mizushima et al and Sakat et al followed with minor modifications. The
reaction mixture was consists of test samples of 100-500 µg/ml and 1%
aqueous solution of bovine albumin fraction, pH of the reaction mixture
was adjusted using small amount of 1N HCl. The samples were
incubated at 37 ºC for 20 min and then heated to 51 º C for 20 min, after
cooling the samples the turbidity was measured at 660nm.( UVVisible
Spectrophotometer Model 371, Elico India Ltd) The experiment was
performed in triplicate.
The Percentage inhibition of protein denaturation was calculated as
follows: Percentage inhibition = (Abs Control –Abs Sample) X 100/ Abs
control

Membrane stabilization
Preparation of Red Blood cells (RBCs) suspension
The Blood was collected from healthy human volunteer who has not taken any
NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) for 2 weeks prior to the
experiment and transferred to the centrifuge tubes. The tubes were centrifuged at
3000 rpm for 10min and were washed three times with equal volume of normal
saline. The volume of blood was measured and re constituted as 10% v/v suspension
with normal saline.
Heat induced haemolysis
The reaction mixture (2ml) consisted of 1 ml test sample of different concentrations
(100 - 500 µg/ml) and 1 ml of 10% RBCs suspension, instead of test sample only
saline was added to the control test tube. Ibuprofen was used as a standard drug. All
the centrifuge tubes containing reaction mixture were incubated in water bath at 56 ºC
for 30min. At the end of the incubation the tubes were cooled under running tap
water. The reaction mixture was centrifuged at 2500 rpm for 5 min and the
absorbance of the supernatants was taken at 560 nm. The experiment was performed
in triplicates for all the test samples. The Percentage inhibition of Haemolysis was
calculated as follows:
Percentage inhibition = (Abs control –Abs sample) X 100/ Abs control

RESULTS & DISCUSSION
Table 9: Synthesis and Characterization
Compound Mol.
Formula
Mol. Structure Mol.
weight
Yield
( % )
M.P TLC
A C19H15N
O4
321.32 80 60-80˚c 0.7
B C19H15Cl
O2
310.77 72 90˚c 0.64
C C21H20O4 336.38 66 110˚c 0.74
D C22H22O5 366.40 60 119˚c 0.72
E C21H20O4 336.38 64 110˚c 0.73
OH
O
N
+
O
-
O
OH
O
Cl
OH
O
O CH3
OH
OH O
O
CH3
O
CH3
O
CH3
OH
O O
CH3
O
CH3

PkCSM
Molecule Depiction- Compound A
Table 10: Molecule properties of Compound A
Descriptor Value
Molecular Weight 321.332
LogP 3.5537
Rotatable Bonds 4
Acceptors 4
Donors 1
Surface Area 138.267

Table :11 Pharmacokinetic properties of Compound A
Property Model Name Predicted
Value
Unit
Absorption Water solubility -5.233 Numeric (log mol/L)
Absorption Caco2 permeability 1.107 Numeric (log Papp in
106 cm/s)
Absorption Intestinal absorption
(human)
95.849 Numeric (% Absorbed)
Absorption Skin Permeability -2.813 Numeric (log Kp)
Absorption P-glycoprotein substrate Yes Categorical (Yes/No)
Absorption P-glycoprotein I
inhibitor
Yes Categorical (Yes/No)
Absorption P-glycoprotein II
inhibitor
No Categorical (Yes/No)

Table 12:Distribution
Property Model Name Predicted Value Unit
Distribution VDss (human) -0.308 Numeric (log L/kg)
Distribution Fraction unbound
(human)
0.015 Numeric (Fu)
Distribution BBB permeability -0.15 Numeric (log BB)
Distribution CNS permeability -1.917 Numeric (log PS)
Table 13:Excretion
Property Model Name Predicted
Value
Unit
Excretion Total Clearance 0.131 Numeric (log ml/min/kg)
Excretion Renal OCT2
substrate
No Categorical (Yes/No)

Table 14: Metabolism
Metabolism CYP2D6 substrate No Categorical (Yes/No)
Metabolism CYP3A4 substrate Yes Categorical (Yes/No)
Metabolism CYP1A2 inhibitior Yes Categorical (Yes/No)
Metabolism CYP2C19 inhibitior Yes Categorical (Yes/No)
Metabolism CYP2C9 inhibitior No Categorical (Yes/No)
Metabolism CYP2D6 inhibitior No Categorical (Yes/No)
Metabolism CYP3A4 inhibitior No Categorical (Yes/No)

Table 15: Toxicity
Toxicity AMES toxicity Yes Categorical (Yes/No)
Toxicity Max. tolerated dose (human) 1.205 Numeric (log
mg/kg/day)
Toxicity hERG I inhibitor No Categorical (Yes/No)
Toxicity hERG II inhibitor Yes Categorical (Yes/No)
Toxicity Oral Rat Acute Toxicity
(LD50)
2.343 Numeric (mol/kg)
Toxicity Oral Rat Chronic Toxicity
(LOAEL)
2.567 Numeric (log
mg/kg_bw/day)
Toxicity Hepatotoxicity No Categorical (Yes/No)
Toxicity Skin Sensitisation No Categorical (Yes/No)
Toxicity T.Pyriformis toxicity 1.027 Numeric (log ug/L)
Toxicity Minnow toxicity -0.376 Numeric (log mM)

Compound B Compound C
Compound D
Compound E

COMPOUNDS 1IS2 1W07 3COX 4COX 6COX
C-1 (C19H15ClO2 ) -366.4 -320.55 -313.04 -87.95 -148.99
C-2 (C19H15NO4) -343.41 -328.1 -324.77 -98.09 -128.87
C-3 (C21H20O4) -340.44 -362.55 -329.09 -56.14 -147.58
C-4 (C21H20O4) -327.9 -313.38 -325.02 -90.59 -151.85
C-5 (C22H22O5) -374.18 -320.76 -337.09 -45.04 -165.93
Table 16: HEX DOCKING SCORES OF COMPOUNDS E-Minimum Scores

COMPOUNDS 1IS2 1W07 3COX 4COX 6COX
C-1 (C19H15ClO2 )
564.79 585.33 485.10 315.50 147.99
C-2 (C19H15NO4)
546.19 446.54 504.41 263.87 228.04
C-3 (C21H20O4)
628.34 530.60 471.59 243.56 250.08
C-4 (C21H20O4)
588.19 484.21 516.65 412.50 320.16
C-5 (C22H22O5)
562.48 659.37 556.27 242.45 256.07
Table 17: E-Maximum Scores

Fig. 1:E-Minimum Value of C5 at 1IS2
Fig. 2: E-Minimum Value of C3 at 1W07

Fig.4: E-Minimum Value
of C2 at 4COX
Fig.3:E-Minimum Value of C5
at 3COX

Fig.5: E-Minimum Value of C5 at 6COX

Table 18: FT-IR spectral data of Chalcones
COMPOUND
WAVE NUMBER
(cm-1)
FUNCTIONAL GROUP
C 1 1605
1706
2851
1197
13441360–1290
3422
C=C (Stetching)
C-O Group stretching
CH-Aromatic stretching
CO-CH2 stretching
(m) N–O symmetric stretch nitro compounds
O–H stretch, H–bonded
C 2 1600
1658
2836
1182
756.68
C=C (Stetching)
CO-CH2 stretching
Aromatic bending Cl
C 3 1228
1636
3447
1581
3447
OH Bending
C-O stretching
CH-CH streching
C 4 3252
1684
1587
1504, 1459
3442
OH stretching
C=O stretching
CH-CH streching
ring C=C
C 5
1580.86
1656.63
3372.01
1062
3372
C=C (Stetching)
CO-CH2 stretching
1-(1-
hydroxynaphthalen-
2-yl)ethanone
1580.86
1456-3565
C=C (Stetching)
O–H stretch
1017 CO-CH2 stretching

Table 19: NMR Spectroscopy of Synthesized Chalcones.
COMPOUND 1HNMR(CDC13,ppm)
Compound A 7.602-7.952(1H;d;CH-Ar) ,6.920-6.922 (1H;d;CO-
H=), 6.532-8.219(8H;m,Ar-H), 8.026 ( OH)
Compound B 3.69 (H;s;OCH3 ,6.912-6.916 (1H;d;CO-H=),
8.00-9.45 (1H;d;CH-Ar)
Compound C 7.604-9.553(1H;d;CH-Ar) ,7.219-7.432
(1H;d;CO-H=) ,7.145-8.577(8H;m,Ar-H) ,
3.69(9H;s;OCH3)
Compound D 7.96-7.98(1H;d;CH-Ar) ,7.96-8.62
(8H;m,Ar-H) 8.62 ( OH) ,3.664(9H;s;OCH3)
Compound E 7.604-7.659(1H;d;CH-Ar) ,7.219-7.432
(1H;d;CO-H=)
7.145-8.577(8H;m,Ar-H) ,8.855 ( OH)
3.73(9H;s;OCH3)

COMPOUND
MOL.
weight
MASS FRAGMENTS
Compound A 321.32 144, 156, 149
Compound B 310.77 144, 166, 112
Compound C 366.38 144, 56, 178
Compound D 366.40 184, 168, 198,128,158
Compound E 336.38 128, 156, 198,182
Table 20: MASS Spectroscopy of Synthesized Chalcones

D:IR DATA.1044 2 ACETIAL NAPTAL SOLID 1/9/2016
3565.34
3050.50
2925.02
1598.51
1517.10
1456.87
1386.45
1269.71
1239.43
1083.10
1015.22
875.80
789.64765.85
709.39
566.46
100015002000250030003500
Wavenumber cm-1
405060708090
100
Transmittance[%]
Page 1/1
Fig.6: FTIR Spectra of 1-(1-hydroxynaphthalen-2-yl)ethanone

D:IR DATA.1045 4 NITRO BENZALDEHYDE SOLID 2/3/2016
3676.64
3422.43
3107.11
2925.05
2851.86
1706.34
1605.48
1522.16
1344.60
1197.90
1017.96
850.34
818.87
772.14
738.84
670.11
100015002000250030003500
Wavenumber cm-1
6065707580859095
100
Transmittance[%]
Page 1/1
Fig.7: FTIR Spectra of Compound A

D:IR DATA.1048 4 CHLORO BENZALDEHYDE SOLID 2/3/2016
3849.753827.60
3732.47
2344.41
100015002000250030003500
Wavenumber cm-1
65707580859095
100
Page 1/1
Fig.8: FTIR Spectra of Compound B

D:IR DATA.1050 VANILLIN SOLID 2/3/2016
3745.74
3670.29
3447.60
2924.83
2854.66
2369.51
1636.12
1019.99
100015002000250030003500
Wavenumber cm-1
65707580859095
100
Transmittance[%]
Page 1/1
Fig.9: FTIR Spectra of Compound C

D:IR DATA.1046 3,4,5-TRIMETHOXY BENZALDEHYDE SOLID 2/3/2016
3646.25
3442.49
2943.28
2842.92
2753.88
2655.04
1684.89
1587.17
1504.79
1459.60
1424.04
1392.09
1330.67
1233.86
1127.67
992.61
845.76
731.07
628.24
100015002000250030003500
Wavenumber cm-1
20406080
100
Transmittance[%]
Page 1/1
Fig.10: FTIR Spectra of Compound D

D:IR DATA.1043 METFORMIN+F4 SOLID 1/7/2016
3676.60
3372.07
3174.13
2972.71
2936.82
2691.29
1567.97
1062.35
937.06
736.87
100015002000250030003500
Wavenumber cm-1
30405060708090
100
Page 1/1
Fig.11: FTIR Spectra of Compound E

Fig.12: Mass Spectra of Compound A

OH
O
N
+
O
-
O
CH2
N
+
O
-
O
Formula Weight: 149.14668
OH
O
.
.
.
Fragmentation Pattern of
Compound A

Fig.13: Mass Spectra of Compound B

OH
O
Cl
O
Cl
.
Cl
.
OH
.
.
Fragmentation Pattern of Compound B

OH
O
OH
O CH3
O
OH
O
CH3
OH
..
O
CH2
.
Fragmentation Pattern of Compound C

OH O
O
CH3
O
CH3
O
CH3
O
CH3
O
CH3
O
CH3
O
..
.
.
O
CH2
OH O
CH2
.
Fragmentation Pattern of Compound D

Fig.16: Mass Spectra of Compound E

OH
O O
CH3
O
CH3
OH
O
CH2
O
CH2
..
. O
.
Fragmentation Pattern of Compound E

ANTI-MICROBIAL STUDIES
1000
(µg/ml)
500
(µg/ml)
250
(µg/ml)
125
(µg/ml)
62.5
(µg/ml)
31.25
(µg/ml)
A 16 12 9 7 4 2
B 15 11 8 3 3 0
C 13 10 9 4 3 0
D 14 11 8 6 4 2
E 11 8 9 4 2 0
Table 21: Zone of inhibition (ZOI) of compounds against Escherichia coli
Comparison of Zone
of inhibition
(Diameter in mm) of
all synthesized
compounds against
Escherichia coli using
conc. 1000, 500, 250,
125 and 62.5µg / ml.
Conc. of
Trimethoprim
(µg/ml) -
-1000 ml
Avg. zone of
inhibition
(Diameter in
mm)
-28mm
Fig.22: Zone of inhibition (ZOI) of Trimethoprim
against Escherichia coli

1000
(µg/ml)
500
(µg/ml)
250
(µg/ml)
125
(µg/ml)
62.5
(µg/ml)
31.25
(µg/ml)
A 15 11 7 4 3 0
B 14 12 9 4 2 0
C 12 11 6 2 2 0
D
16 14 9 6 4 2
E
10 7 5 4 2 0
Table 22:Zone of inhibition (ZOI) of compounds against Bacillus substills
Fig.23:Zone of inhibition (ZOI) of Trimethoprim against Bacillus substills
Comparison of Zone
of inhibition
(Diameter in mm) of
all synthesized
compounds against
Bacillus substills using
conc. 1000, 500, 250,
125 and 62.5µg / ml.
Conc. of
Trimethoprim
(µg/ml) -
-1000 ml
Avg. zone of
inhibition
(Diameter in
mm)
-30mm
0
2
4
6
8
10
12
14
16
ZoneofInhibition(mm)
Concentration
B.subtilis

1000
(µg/ml)
500
(µg/ml)
250
(µg/ml)
125
(µg/ml)
62.5
(µg/ml)
31.25
(µg/ml)
A 16 12 9 7 3 0
B 14 10 8 6 4 0
C 12 9 7 4 2 0
D
13 11 9 4 2 0
E
10 10 9 6 3 0
Table 23:Zone of inhibition (ZOI) of compounds against Aspergillus niger
Fig.24:Zone of inhibition (ZOI) of Ciprofloxacin against
Aspergillus niger
Comparison of Zone
of inhibition
(Diameter in mm) of
all synthesized
compounds against
Aspergillus niger
using conc. 1000, 500,
250, 125 and 62.5µg /
ml.
Conc. of
Ciprofloxacin
(µg/ml) -
-1000 ml
Avg. zone of
inhibition
(Diameter in
mm)
-26mm
0
2
4
6
8
10
12
14
16
ZoneofInhibition(mm)
Concentraion
Aspergillus niger

1000
(µg/ml)
500
(µg/ml)
250
(µg/ml)
125
(µg/ml)
62.5
(µg/ml)
31.25
(µg/ml)
A 14 10 8 4 2 0
B 13 11 9 3 2 0
C 12 10 7 4 2 0
D
11 11 8 4 2 0
E
13 10 9 4 0
Table 24: Zone of inhibition (ZOI) of compounds against Candida albicans
Fig.25: Zone of inhibition (ZOI) of Ciprofloxacin against Candida albicans
Comparison of Zone
of inhibition
(Diameter in mm) of
all synthesized
compounds against
Candida albicans
using conc. 1000, 500,
250, 125 and 62.5µg /
ml.
Conc. of
Ciprofloxacin
(µg/ml) -
-1000 ml
Avg. zone of
inhibition
(Diameter in
mm)
-26mm
0
2
4
6
8
10
12
14
ZoneofInhibition
Concentration
candida albicans
A
B
C
D
E

Concentrati
on
µg/ml
Sample-
A
Sample-
B
Sample-
C
Sample-
D
Sample-
E
STD
100 60.52 59.68 47.749 60.67 83.70 32.72
200 69.51 69.65 72.04 69.51 87.915 85.94
300 97.88 93.95 63.90 91.005 68.4 80.61
400 98.58 98.64 91.84 98.44 83.98 74.99
500 99.15 99.06 29.632 98.78 60.9 75.27
table 25: Percentage Inhibition of Albumin Denaturation Studies
Concentratio
n µg/ml
Sample-
A
Sample-
B
Sample-
C
Sample-
D
Sample-
E
STD
100 75.118 80.72 68.58 79.36 88.190 77.24
200 82.758 59.246 65.35 74.94 79.87 86.322
300 73.08 90.82 56.02 73.166 66.036 79.95
400 75.11 89.20 59.50 73.251 61.962 78.514
500 72.57 73.08 74.43 69.26 57.71 75.88
ANTI INFLAMMATORY STUDIES
Table 26: Percentage Inhibition of Heat induced hemolysis

SUMMARY & CONCLUSION
The novel chalcones have been synthesized by Claisen–Schmidt
condensation reaction. The synthesis of the chalcone is a single step
method. The synthesized chalcone derivatives were undergone
physicochemical characterization and the obtained results are given
in Table 6. The yields of the synthesized compounds were found to be
significant.
The structure of the synthesized compounds was confirmed by IR, Mass
and 1HNMR.
Conclusion
The synthesized compounds were characterized by TLC, melting point, IR
spectroscopy, 1HNMR Spectroscopy and mass spectroscopy. The results
obtained from this study confirmed that the product has formed.
Henceforth viewing these characteristic properties more compounds can
be synthesized and subjected to pharmacological evaluation. These
Chalcone derivatives have biological activities like anti-bacterial and anti-
inflammatory may be a pave for synthesis and characterization of some
new chalcone derivatives.

All the synthesized compounds were tested for in vitro antibacterial activity by agar
dilution method. The MIC of the compounds against 16 gram-positive bacterial strains
is presented in [Table 21-26]. All the Compounds showed good activity against all
bacterial strains than trimethoprim and ciprofloxacin taken as reference standards.
The compounds showed moderate to efficient activity against all bacterial strains
taken for the screening.
The in vitro anti-inflammatory activity was performed by inhibition of bovine albumin
denaturation method and heat induced hemolytic method.
The inhibitory activity of the compounds was compared with the control and the
significance factor “p” was less than 0.001 for all the compounds. The inhibitory
activity of the compounds was compared with the control and the significance factor
“p” was less than 0.001 for all the compounds. The result of the anti-inflammatory
activity was given in table 25&26.
In an Albumin Denaturation Studies, Sample-A Shown 82.758% inhibition at 200
µg/ml, Sample-B 90.82 % at 300 µg/ml, Sample-C 74.43 % at 500 µg/ml, Sample-D
79.36 % at 100 µg/ml & Sample-E 88.190 % at 100 µg/ml.
In Heat induced hemolysis, Sample-A Shown 99.15 % inhibition at 500 µg/ml, Sample-
B 99.06 % at 500 µg/ml, Sample-C 91.84 % at 300 µg/ml, Sample-D 98.78 % at 500
µg/ml & Sample-E 85.94 % at 200 µg/ml.

FUTURE SCOPE
The existing designed analogs (Compound A-E) can be
further modified so as to include substituted pyrazolines,
pyrimidines, Oxazoles, hydrazones, benzodiazepines etc which
can produce further substituted derivatives. Such analogs can
be synthesized, and evaluated for their Anthelmentic and anti-
tubercular activities and other activities.
It would be interesting to deduce the structure of potent
compounds for the activity claimed, they may be our lead
molecules and there is a possibility to extend the lead molecule
towards drug design using various drug design software’s like
maestro, glide, scigress, autodock etc.

REFERENCE
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of technolgi Mara,Selangor, , pp.1, 1-11.(2006)
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Synthesis and Antimicrobial Activity of Some Novel Chalcones of 2-Hydroxy -1-
Acetonapthone and 3-Acetyl Coumarin. E-Journal of Chemistry.2006,3(4), 236-
241.

Jayapal, M.R.; and Sreedhar, N.Y. Synthesis of 2, 6dihydroxy substituted chalcones
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Siva sankerreddy et al.Synthesis and evaluation of novel pyrrolidine chalcone
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