Page | 908

In silico toxicity prediction, synthesis, characterization, antimicrobial and

antioxidant activity of different di substituted chalcones

Shaik Ammaji 1, *

, Cheekurthi Sunddep 1, Koduru Sandeep

1, Kunchala Ashok

1, Kancharala Praveen

1,

Badugu Sai Murali 1

1 NRI College of Pharmacy, pothavarapadu, agiripalli, Vijayawada, Krishna (Dt), Andhra Pradesh. *corresponding author e-mail address: Shaik.ammaji8@gmail.com

ABSTRACT

Right now the amalgamation of novel arrangement of 4'- chloro-3'- nitro-phenyl-(3-keto-1,2diene-1-flurobenzene), 4'- chloro-3'nitro-

phenyl-(3-keto-1,2diene-1-chlorobenzene),4'- chloro-3'- nitro-phenyl-(3-keto-1,2diene-1-thiophene),4'- chloro-3'nitro-phenyl-(3-keto-

1,2diene-1-pyridine), 4'- chloro-3'nitro-phenyl-(3-keto-1,2diene-1-furon).The target mixes were integrated by the Claisen-schimidt

buildup utilizing corrosive and base as a response impetus. insilico enhancement strategies by utilization of various information base like

molinspiration for atomic properties, bioactivity, ochem for organic information, pre ADME for pharmacokinetic properties, preToxicity

for harmfulness profile of the mixes, swiss ADME for pharmacokinetic property, Swiss lethality for natural danger of the mixes, and

Osiris(datawarrior) for poisonous quality forecast for dynamic lead particles ID. From the outcome mixes indented as dynamic leads they

used to assess distinctive organic action. The mixes additionally finish the amees assessment for the most part for mutagenecity

discovery that mixes shows mutagencity towards the test living being they likewise safe to hinder cytochrome P450 compound subunits

like cyp1A2, cyp2C9, cyp2C19 which are situated in endoplasmic reticulum. Alpha beta unsaturated chalcones have fantastic cell

reinforcement and antimicrobial action so the orchestrated mixes were screened for their antimicrobial by utilizing five bacterial strains

and three parasitic strains and cancer prevention agent action by DPPH technique. From hostile to oxidant results compound 3a, 3b, 3c

show critical action the measure esteems are closer to standard medication esteem. Antimicrobial movement results the compound 3a,

3c, 3e indicated noteworthy action against Bacillus subtilis, E Coli, Salmonella tyhphi, Pseudomonas aeruginosa though the compound

3b, 3d demonstrated moderate activitycompared to standard medication vale. Compound 3b, 3d demonstrated fantastic antifungal action

against Candida albicans, Aspergillusniger, Alternariaalternata. The mixes 3a, 3c, 3e show moderate antifungal movement when

contrasted with standard worth.

Keywords:molinspiration; Osiris; ochem; preADME; antioxidant; antimicrobial activity.

1. INTRODUCTION

Chalcones are α,βunsaturated ketone they are focal center

for acombined assortment of organic mixes. Claisen-Schmidt

buildup between aromatic ketone and fragrant aldehyde to give

chalcone the response catalyzed by corrosive and base under

homogeneous or heterogeneous conditions [1,2] they are open

chain antecedent particle for biosynthesis of flavanoids,

isoflavnoids and poly phenolic derivatives[3]. They exist as two

isomeric structures cis and trans. Trans ismore steady than cis

structure [4]. The mixes have enormous no of replaceable

hydrogen particles that permit to blended a huge assortment of

subordinates like pyrazoles, imidazole, thiazole, triazole, oxazole

and so on, they show distinctive kind of organic exercises like

antigout [6], hostile to histamine [7], antioxidant [8], antiodesity

[9], hypotics [10], antispasmodic [11], antiprotozal [10] and so on.

These days, various similar pharmacological examinations of the

chalcones have indicated great cancer prevention agent movement

with low reactions. In past reports the greater part of the chalcones

integrated by utilizing single subbed ketone with single or di

subbed aldehydes however right now di subbed ketone with

various subbed aldehydes utilized for blend of various chalcone

subsidiaries.

2. MATERIALS AND METHODS

2.1. Materials.

All the chemicals and reagents were obtained in synthetic

grade from commercial sources. Microwave irradiation was

carried out in LG domestic microwave oven. Reaction was

monitorby TLC (silica gel). 4’Chloro-3’nitro MKBX1257V Sigma

Aldrich Acetophenone, Potassium hydroxide N1400361 Avra

synthesis (85%) P-Chlorobenzaldehyde L126101406 Loba

chemic, 2-Fluorobenzaldehyde A301696 Spectro chem., 2-

Furaldehyde (99%) N1601838 Avra synthesis Pyridine-4-

carboxalde N1602027 Avra synthesis -hyde(98%) 3-

Fluorobenzaldehyde N1610254 Avra synthesis (98%) 3-

Chlorobenzaldehyde B300201 Spectro chem., 2-

Thiophenecarboxalde N1703574 Avra synthesis- hyde(98%), 2-

Chlorobenzaldehyde N1810073 Avra synthesis, 4-

Fluorobenzaldehyde N1800433 Avra synthesis (98%)3-Hydroxy

benzaldehyde N1701409 Avra synthesis (97%)2-

Hydroxybenzaldehyde N1800578 Avra synthesis (98%) 4-

Hydroxybenzaldehyde N1800160 Avra synthesis.

2.2. Method.

2.2.1. Synthesis of Chalcones.

A mixture of ketone (0.05mol), appropriate aldehyde

(0.05mol) and 10% aqueous sodium hydroxide (10ml) in ethanol

Volume 9, Issue 1, 2020, 908 - 913 ISSN 2284-6808

Open Access Journal Received: 04.03.2020 / Revised: 18.03.2020 / Accepted: 18.03.2020 / Published on-line: 21.03.2020

Original Research Article

Letters in Applied NanoBioScience https://nanobioletters.com/

https://doi.org/10.33263/LIANBS91.908913

In silico toxicity prediction, synthesis, characterization, antimicrobial and antioxidant activity of different di substituted

chalcones

Page | 909

(30ml) should be stirred at room temperature for about 3-24 h. The

reaction mixture after achieving the desired spot in the TLC

should transfer into crushed ice to form the precipitate. The

precipitate should be filtered, washed with distilled water and

recrystallized with chloroform.

Figure 1. Synthesis of chalcones.

2.2.2. Antimicrobial activity.

Antibacterial action of the combined mixes was tried

against five bacterial strains and three parasitic strains utilizing

agar well dispersion technique [15-18]. Dimethyl sulfoxide was

utilized as dissolvable control. The bacterial culture was

vaccinated on supplement agar and contagious culture was

immunized on potato dextrose agar media (20 ml). The test mixes

were broken up in DMSO to get a convergence of 12.79M and 100

µL of this example was stacked into the wells of agar plates

legitimately. Plates immunized with the microorganisms were

brooded at 37°C for 24 h and the parasitic culture was hatched at

25°C for 72 h. All conclusions were done in triplicates. The

Streptomycin (1.71M and 0.85M) and Griseofulvin (3.26M and

1.6M) were utilized as standard medications for antibacterial and

antifungal exercises individually. After the brooding time frame,

the base restraint zone at which the microorganism development

was hindered was estimated in µg/mL [19-24].

2.2.3. Antioxidant activity Free radical scavenging activity by

DPPH method.

Free radicalscavenging capacities of synthesized

compounds were determined according to the reported procedure

[25-28]. The newly synthesized compounds at different

concentrations (25-100 µg/mL) were added to each test tube and

volume was made up to 4 ml using methanol. To this, 3 ml of

0.004% DPPH in methanol was added and the mixtures were

incubated at room temperature under dark condition for 30 min.

The absorbance was recorded at 517 nm using UV Visible

spectrophotometer (Shimadzu UV-1800, Japan).

Butylatedhydroxy toluene (BHT), dissolved in distilled water was

used as a reference [29-31]. The control sample was prepared

using the same volume without any compound and BHT, 95%

methanol served as blank. Test was performed in triplicate and the

results were averaged [32-36].

Radical scavenging activity was calculated using the formula:

Percentage of radical scavenging activity = [(Acontrol–Atest)/Acontrol]

× 100

Where Acontrol is the absorbance of the control sample (DPPH

solution without test sample) and Atest is the absorbance of the test

sample (DPPH solution+test compound).

3. RESULTS

3.1. Spectral analysis.

1-(4-chlro-3-noitrophenyl)-3-(4-fluorophenyl)pro-2-ene-1-one,

(3a), Percentage yield: 85%, m.p:14.-142oC; IR (KBr cm-1) 689

(C-Cl), 1024 (C-F), 1545 (NO2), 1649 (C=O); 1 HNMR (CDCl3

400Mz), δ (ppm) 7.65 (d 1H HαJ= 16.1Hz), 7.91 (d IH HβJ=

15.1Hz), 7.21-8.07 (m Ar-H); 13 CNMR (400MHz CDCl3), δ

(ppm), 121.3 (C-2), 145.1 (C-3), 189.7 (C=O, C-1), 124.9-148.1

(C-1’- C-6’ aromatic carbons), 115.4-162.1 (C-1’’-C-6’’ aromatic

carbons); LCMS: m/z: 305, (M+1=99.08); elemental analy: C15

H9ClFNO3, C-58.94, N-4.59, H-2.97 found C-58%, N-4.5%, H-

2.9%.

1-(4-chlro-3-noitrophenyl)-3-(2-chlorophenyl)pro-2-ene-1-one,

(3b), Percentage yield: 80%, m.p:130-135oC; IR (KBr cm-1) 684

(C-Cl), 689 (C-Cl), 1547 (NO2), 1649 (C=O); 1 HNMR (CDCl3

400Mz), δ (ppm) 7.63 (d 1H HαJ= 16.5Hz), 7.89 (d IH HβJ=

16.1Hz), 7.21-8.10 (m Ar-H); 13 CNMR (400MHz CDCl3), δ

(ppm), 121.3 (C-2), 145.1 (C-3), 189.7 (C=O, C-1), 124.9-148.9

(C-1’- C-6’ aromatic carbons), 126.7-134.0 (C-1’’-C-6’’ aromatic

carbons); LCMS: m/z: 321, (M+1=99.08); elemental analy: C15

H9Cl2NO3, C-55.9, N-4.35, H-2.82 found C-56%, N-4.0%, H-

2.5%.

1-(4-chlro-3-noitrophenyl)-3-(thiophen)pro-2-ene-1-one, (3c),

Percentage yield: 80%, m.p:120-125oC; IR (KBr cm-1) 687 (C-

Cl), 775 (C-S-C), 1547 (NO2), 1649 (C=O); 1 HNMR (CDCl3

400Mz), δ (ppm) 7.63 (d 1H HαJ= 16.5Hz), 7.85 (d IH HβJ=

16.1Hz), 7.21-8.15 (m Ar-H); 13 CNMR (400MHz CDCl3), δ

(ppm), 121.3 (C-2), 134.1 (C-3), 189.7 (C=O, C-1), 129.1-140.3

(C-1’’-C-4’’thiophen carbons), 130.2-148.1 (C-1’- C-6’ aromatic

carbons); LCMS: m/z: 292, (M+1=99.08); elemental analy: C15

H10ClNO3S, C-53.1, N-4.77, H-2.75 found C-53%, N-4.7%, H-

2.5%.

1-(4-chlro-3-noitrophenyl)-3-(pyridine)pro-2-ene-1-one, (3d),

Percentage yield: 85%, m.p:95-98oC; IR (KBr cm-1) 689 (C-Cl),

1547 (NO2), 1640 (C=N), 1649 (C=O); 1 HNMR (CDCl3 400Mz),

δ (ppm) 7.65 (d 1H HαJ= 15.5Hz), 7.80 (d IH HβJ= 16.1Hz),

7.21-8.27 (m Ar-H); 13 CNMR (400MHz CDCl3), δ (ppm), 127.0

(C-2), 143.4 (C-3), 189.7 (C=O, C-1), 122.7-154.7 (C-1’’-C-5’’

pyridine carbons), 124.9-148.1 (C-1’- C-6’ aromatic carbons);

LCMS: m/z: 288, (M+1=99.04); elemental analy: C14 H9ClN2O3;

C-58.2, N-9.77, H-3.14 found C-58%, N-9.7%, H-3.0%.

1-(4-chlro-3-noitrophenyl)-3-(furan)pro-2-ene-1-one, (3e),

Percentage yield: 80%, m.p:120-125oC; IR (KBr cm-1) 686 (C-

Cl), 1545 (NO2), 1649 (C=O); 1 HNMR (CDCl3 400Mz), δ (ppm)

7.63 (d 1H HαJ= 16.5Hz), 7.85 (d IH HβJ= 16.1Hz), 7.21-8.15 (m

Ar-H); 13 CNMR (400MHz CDCl3), δ (ppm), 120.9 (C-3), 127.3

(C-2), 189.7 (C=O, C-1), 112.7-151.5 (C-1’’-C-4’’ furan carbons),

124.9-148.1 (C-1’- C-6’ aromatic carbons); LCMS: m/z: 292,

(M+1=99.08); elemental analy: C13 H8ClNO4; C-56.23, N-5.04, H-

2.90 found C-56.2%, N-5.0%, H-2.5%.

3.2. In silico and toxicity prediction.

Insilico toxicity prediction for synthesized compounds

carried out by using four online soft wares Molinspiration -

www.molinspiration.com; www.swissadme.ch.in,

https://ochem.eu , www.organic-chemistry.org/prog/peo/tox.html.

Shaik Ammaji, Cheekurthi Sunddep, Koduru Sandeep, Kunchala Ashok, Kancharala Praveen, Badugu Sai Murali

Page | 910

Table 1.Molinspiration results of physicochemical properties of di substituted chalcones.

COMP ID MW clogP n AH n DH TPSA n rotb

3A 305 4.03 4 0 62.9 4

3B 322 4.31 3 0 62.8 4

3C 293 3.58 3 0 62.8 4

3D 288 2.51 4 0 88.19 4

3E 277 2.94 4 0 75.7 4

MW, molecular weight; nDH, number of H-bond donors; nAH, number of H-bond acceptors; TPSA, topological polar surface area; cLogP,

Partition coefficient.

Table 2. Molinspiration bioactive score value of disubstitutedchalcones.

COMP

ID

GPCR

ligand

Ion channel

modulator

kinase

inhibitor

Nuclear

receptor ligand

protease

inhibitor

enzyme

inhibitor

3A -0.4 -0.29 -0.4 -0.26 -0.45 -0.18

3B -0.43 -0.32 -0.56 -0.27 -0.52 -0.28

3C -0.7 -0.55 -0.58 -0.55 -0.69 -0.36

3D -0.2 -0.19 -0.24 -0.44 -0.39 -0.03

3E -0.77 -0.76 -0.86 -0.62 -0.92 -0.46

If bioactivity score is >0, it is an active compound while <-5.0 is an inactive compound and range between -5.0 to 0.0 is

moderately active compounds.

Table 3. preADMET results of disustitutedchalcones.

COMP ID HIA (%) In vitro

Caco2(nm/sec)

MDCK

(nm/sec)

PPB BBB CYP 2C9, 19

3a 98.4 15.1 0.43 96.8 0.25 INHIBITOR

3b 98.4 7.2 6.94 95.5 0.039 INHIBITOR

3c 96.6 1.18 1.47 96.8 1.44 INHIBITOR

3d 97.1 8.4 4.93 94.6 0.03 INHIBITOR

3e 95.3 2.16 3.55 98.8 1.38 INHIBITOR

HIA(%), Percentage human intestinal absorption; PCaco2 (nm/sec), Caco2 cell permeability in nm/sec; MDCK (nm/sec), Madin-Darby

canine kidney cell permeabity in nm/sec; PPB(%), in vitro plasma protein binding (percentage); BBB, in vivo Blood-Brain Barrier

penetration.

Table 4. preADMET toxicity values of di substituted chalcones.

ID algae_at Ames_test TA100_1

0RLI

TA100_NA TA1535_1

0RLI

TA1535_NA Carcino_

Mouse

Carcino_R

at

3a 0.026515 mutagen Positive negative Negative Positive Positive Negative

3b 0.015208 mutagen Positive negative Positive Positive Positive Negative

3c 0.0310418 mutagen Positive negative Negative Negative Positive Negative

3d 0.0651226 mutagen Positive positive Negative Positive Positive Negative

3e 0.0611501 mutagen Positive negative Positive Negative Positive Negative

mutagenicity of amessalmonealla TA100, TA98, TA1535 Species result positive (+) shows compound is mutagenic negative (-) means non

mutagenic. In rodent carcinogenicity 2 years assay of rat and mouse by backward elimination and Rprop neural net method result Negative (-)

indicate non carcinogenic, positive (+) indicate carcinogenic.

Table 5. OCHEM chemical and biological data of di substituted chalcones.

Comp ID Ames CYP1A2 CYP2C9 CYP2C19

CYP2D6

CYP3A4 Melting

point(0c)

pyrolsis point

(celsius)

3a Active + + + + - 140 180

3b Active + + + - - 130 180

3c Active + + + - - 120 180

3d Active + + + - - 95 180

3e Active + + + - - 92 170

ames test used to determine mutagenicity of the sample result inactive means not shows any mutational change in test organism, CYP1A2,

2C9, 2C19, 2D6, 3A4 enzyme inhibition from the above results positive (+) means enzyme inhibiting property, negative (-) means drug does

not inhibit the enzyme, by using these software tool also determine the melting point and pyrolsis point (chemical decomposition of organic

material by application of heat) of the compounds.

Table 6 . Swiss physicochemical properties and bioactive score values of substituted chalcones.

comp id MW No of heavy

atoms

no of hydrogen

aceptors

no of hydrogen

donars

no of rotable

bonds

Log P Log S TPSA

3A 305 21 4 0 4 4.03 -4.57 62.9

3b 322 21 3 0 4 4.31 -5.82 62.8

3c 293 19 3 0 4 3.58 -5.02 88.19

3d 288 20 4 0 4 2.51 -4.37 75.7

3e 277 19 4 0 4 2.94 -4.82 76

Description: Swiss ADME web tool predict the molecular weight, no of heavy atoms present in the molecule, no ofhydrogen acceptors, hydrogen

donar, Log P (partition coeffient) , Log S(Solubility), TPSA, topological polar surface area. Lipinski, Ghose and Veber rules states that most

molecules with good membrane permeability have logP ≤ 5, logS ≤ 5, molecular weight ≤500, number of hydrogen bond acceptors ≤10, and

number of hydrogen bond donors ≤ 5, topological polar surface area (TPSA) < 140 Ǻ2 and number of rotatable bonds (n rotb) < 10.

In silico toxicity prediction, synthesis, characterization, antimicrobial and antioxidant activity of different di substituted

chalcones

Page | 911

Table 7 . Swiss pharmacokinetic properties of di substituted chalcones.

Comp id

GI Absortion BBR CYP

1A2

CYP2

C9

CYP2C

19

CYP2D

6

CYP3

A4

Log Kp (skin

permeation) cm/sec

Lipinsk bioavailbilit

y score

3a high yes + + + + - -5.11 yes 0.55

3b high yes + + + - + -5.11 yes 0.55

3c high yes + + + - + -5.11 yes 0.55

3d high yes + + + - - -4.83 yes 0.55

3e high yes + + + - - -4.83 yes 0.55

Description: This tool used to determine pharmacokinetic properties like GI absorption, BBR, CYP1A2, 2C9, 2D6, 3A4. From the above result yes

means molecule have enzyme inhibiting property, No means molecule not having the enzyme inhibiting property, Log kp(skin permeability) , lipinsk,

bioavailability Score.The bioactivity scores (≥ 0.00) may refer to considerable biological active compound, if the bioactivity scores (-5.0 to 0.0) it is

moderately active and finally if the bioactivity scores (< -5.0) it is inactive.

Table 8. Swiss percentage inhibition of di substituted chalcones. comp

id

enzyme GPCR Oxidoredu

ctase

Prot

ease

lignad

gated ion

channel

primary

active

transport

other cytosolic

protein

nuclear

recepto

r

kinase ligase cytochrome

P450

voltage

gated ion

channel

suface

antigen

3a 20 20 13.3 6.7 26.7 6.7 6.7 0 0 0 0 0 0

3b 20 20 13.3 6.7 26.7 6.7 6.7 0 0 0 0 0 0

3c 20 20 13.3 6.7 26.7 6.7 6.7 0 0 0 0 0 0

3d 13.3 6.7 20 6.7 13.3 6.7 0 0 6.7 0 20 0 0

3e 13.3 6.7 20 6.7 13.3 6.7 0 0 6.7 0 20 0 0

Table 9. Osiris (data warrior) molecular properties of di substituted chalcones.

comp id MW no of hydrogen

acceptors

no of hydrogen

donars

no of rotable

bonds

cLog P cLog S TPSA

DL

3A 305 4 0 4 4.03 -4.57 62.9 5.03

3b 322 3 0 4 4.31 -5.82 62.8 4.94

3c 297 3 0 4 3.58 -5.02 88.19 3.58

3d 288 4 0 4 2.51 -4.37 75.7 5.01

3e 277 4 0 4 2.94 -4.82 76 4.92

Drug- likeness. According to Lipinski rule cLog p ≤5, Clog S<-5, MW ≤500, nALH ≤10, and nDLH ≤5 drug likness(DL) >4.

Table 10. Osiris (data warrior) toxicity prediction of di substituted chalcones.

CompCode MU TU RE IR

3A None None None None

3B None None None None

3C None None None None

3D None None None None

3E None None None None

Toxicity like mutagenic, tumorigenic, irritant and reproductive risks were also predicted using OSIRIS Property. From the results of insilico

data bases all the compounds are non carcinogenic, toxicity free molecule inhibit CYP 2C9, 2C19 enzymes act as active lead molecule.

Table 11. Antibacterial activity results of synthesized compounds (3a-3e.).

Zone of inhibition in mm(SD±Mean)

Comp id Concentration(mg/ml) S. a ± S.D* B. s ±S.D* E. c ± S.D* S. t ± S.D* P. a ±S.D*

3a 1.0 20 ± 0.11 18 ± 0.16 16 ± 0.15 11 ± 0.18 12 ± 0.14

3b 1.0 14 ± 0.12 14 ± 0.60 13 ± 0.21 9 ± 0.12 ± 0.16 00

3c 1.0 15 ± 0.15 12 ± 0.16 14 ± 0.21 13 ± 0.15 13 ± 0.16

3d 1.0 13 ± 0.16 14 ± 0.16 12 ± 0.19 15 ± 0.10 12 ± 0.18

3e 1.0 21 ± 0.16 18 ± 0.13 16 ± 0.17 13 ± 0.18 13 ± 0.15

streptomycin 24 ± 0.16 21 ± 0.12 18 ± 0.11 16 ± 0.19 15 ± 0.14

Each value is the mean of three replicate determinations ± standard deviation; S. a - Staphylococcus aureus;

B. s Bacillus subtilis; E. c - Escherichia coli; S. t - Salmonella tyhphi; P. a - Pseudomonas aeruginosa

Table 12. Antifungal activity results of synthesized compounds (3a-3e).

Comp id Concentration(mg/ml) C. a ± S.D* A. n ± S.D* A. a ± S.D*

3a 1.0 10 ± 0.14 11 ± 0.16 8 ± 0.12

3b 1.0 12 ± 0.15 16 ± 0.18 10 ± 0.15

3c 1.0 10 ± 0.17 11 ± 0.19 12 ± 0.12

3d 1.0 13 ± 0.16 17 ± 0.11 13 ± 0.19

3e 1.0 10 ± 0.15 12 ± 0.10 8 ± 0.11

griseoflavin 14 ± 0.12 19 ± 0.15 16 ± 0.13

Each value is the mean of three replicate determinations ± standard deviation; C. a - Candida albicans;

A. n - Aspergillus niger; A. a – Alternaria alternata

Table 13. IC50 values DPPH radical scavenger results of synthesized compound (3a-3e).

Test compound IC 50 µg/ml values DPPH assay

3a 85.03 ± 0.19

3b 88.62 ± 0.10

3c 91.25 ± 0.05

3d 61.88 ± 0.01

Shaik Ammaji, Cheekurthi Sunddep, Koduru Sandeep, Kunchala Ashok, Kancharala Praveen, Badugu Sai Murali

Page | 912

Test compound IC 50 µg/ml values DPPH assay

3e 64.43 ± 0.00

BHT 95.25 ± 0.05

Each value is expressed as mean ± SD of three replicates; Stda BHT used as standard for DPPH radical scavenging activity.

The active lead molecules detected by using insilico

databases. The above results of insilico databases the compound

act as active lead molecule so they used to synthesis so many

heterocyclic derivatives, directly evaluate the biological activity.

From the antimicrobial results 3a, 3c, 3e compounds shows

excellent anti bacterial activity, 3b, 3d show excellent anti fungal

activity remain compounds show moderate activity, the 3a, 3b, 3c

shows good anti oxidant activity by DPPH method the values are

nearer to standard drug value.

4. CONCLUSIONS

Disubstitutedchalcones were combined from the beginning

material of di substituted ketone, it hasone electron pulling back

gathering and one electron discharging gathering. These mixes

described by IR, NMR, MASS. the aftereffects of insilico

databases all the compound go about as dynamic lead atom so they

straightforwardly assess for its organic action The mixes have

brilliant antimicrobial and against oxidant action the qualities are

closer to standard medication esteem. At long last reason that in

future these chalconetookas a middle of the road to combination

pyrazole, imidazole, quinoline, thiazole subordinates and assess

distinctive organic exercises.

5. REFERENCES

1. Elavarasan, M.; Thendral, M.T.; Shafi, S.S.Ayntheisis and

biological evaluation of chalcone derivatives. Inter jour pharm

scien and research 2018, 9, 1969-1973,

https://doi.org/10.13040/IJPSR.0975-8232.9(5).1969-73.

2. Ni, L.; Meng, C.Q.; Sikorski, J.A. Recent advances in

therapeutic chalcones. Expert Opinion on Therapeutic Patents

2004, 14, 1669-1691,

https://doi.org/10.1517/13543776.14.12.1669.

3. Sahu, N.K.; Balbhadra, S.S.; Choudhary, J.; Kohli, D.V.

Exploring pharmacological significance of chalcone scaffold: A

review. Curr. Med. Chem.2012, 19, 209–

225,https://doi.org/10.2174/092986712803414132.

4. Gomes, M.N.; Muratov, E.N.; Pereira, M.; Peixoto, J.C.;

Rosseto, L.P.; Cravo, P.V.L.; Andrade, C.H.; Neves, B.J.

Chalcone Derivatives: Promising Starting Points for Drug

Design. Molecules 2017, 22, 1210,

https://doi.org/10.3390/molecules22081210.

5. Evranos, A.B.; Ertan, R. Chemical and structural properties

of chalcones I. FABAD J. Pharm. Sci.2011, 36, 223–242.

6. Kim, D.W.; Curtis-Long, M.J.; Yuk, H.J.; Wang, Y.; Song,

Y.H.; Jeong, S.H.; Park, K.H. Quantitative analysis of phenolic

metabolites from different parts of Angelica keiskei by HPLC–

ESI MS/MS and their xanthine oxidase inhibition. Food

Chem.ol2014,153,20–27.

http://dx.doi.org/10.1016/j.foodchem.2013.12.026. 7. Yamamoto, T.; Yoshimura, M.; Yamaguchi, F.; Kouchi, T.;

Tsuji, R.; Saito, M.; Obata, A.; Kikuchi, M. Anti-allergic activity

of naringeninchalcone from a tomato skin extract. Biosci.

Biotechnol. Biochem.2004, 68, 1706–

171,https://doi.org/10.1271/bbb.68.1706.

8. Aoki, N.; Muko, M.; Ohta, E.; Ohta, S. C-

geranylatedchalcones from the stems of Angelica keiskei with

superoxide-scavenging activity. J. Nat. Prod.2008, 71, 2008,

1308–1310,https://doi.org/10.1021/np800187f.

9. Birari, R.B.; Gupta, S.; Mohan, C.G.; Bhutani, K.K.

Antiobesity and lipid lowering effects of Glycyrrhizachalcones:

Experimental and computational studies. Phytomedicine2011,

18, 795–801, https://doi.org/10.1016/j.phymed.2011.01.002.

10. Chen, M.; Christensen, S.B.; Blom, J.; Lemmich, E.;

Nadelmann, L.; Fich, K.; Theander, T.G.; Kharazmi, A.

Licochalcone A, a novel antiparasitic agent with potent activity

against human pathogenic protozoan species of Leishmania.

Antimicrob. Agents Chemother. 1993, 37, 2550–2556,

https://dx.doi.org/10.1128%2Faac.37.12.2550.

11. Cho, S.; Kim, S.; Jin, Z.; Yang, H.; Han, D.; Baek, N.I.; Jo,

J.; Cho, C.W.; Park, J.H.; Shimizu, M.; Jin,

Y.H.Isoliquiritigenin, a chalcone compound, is a positive

allosteric modulator of GABA A receptors and shows hypnotic

effects. Biochem.Biophys. Res. Commun. 2011,413, 637–

642,https://doi.org/10.1016/j.bbrc.2011.09.026.

12. Fowler, K.; Fields, W.; Hargreaves, V.; Reeve, L.; Bombick,

B. Development, qualification, validation and application of the

Ames test using a VITROCELL® VC10® smoke exposure

system. Toxicology Reports 2018, 5, 542-551,

https://doi.org/10.1016/j.toxrep.2018.04.003.

13. Dillon, D.; Combes, R.; Zeiger, E. The effectiveness of

Salmonella strains TA100, TA102 and TA104 for detecting

mutagenicity of some aldehydes and peroxides. Mutagenesis

1998, 13, 19-26, https://doi.org/10.1093/mutage/13.1.19.

14. Miller, W.H.; Dessert, A.M.; Roblin,

jr.R.O.heterocyclicsulphonamides as a cabonic anhydrase

inhibitors. J. Am. Chem. Soc.1950,72,4893-4896,

https://doi.org/10.1021/ja01167a012.

15. Sushko, I.; Novotarskyi, S.; Korner, R.; Pandey, A.K.; Rupp,

M.; Teetz, W.; Brandmaier, S.; Abdelaziz, A.; Prokopenko,

V.V.; Tanchuk, V.Y.; Todeschini, R.; Varnek, A.; Marcou, G.;

Ertl, P.; Potemkin, V.; Grishina, M.; Gasteiger, J.; Schwab, C.;

Baskin, II; Palyulin, V.A.; Radchenko, E.V.; Welsh, W.J.;

Kholodovych, V.; Chekmarev, D.; Cherkasov, A.; Aires-de-

Sousa, J.; Zhang, Q.Y.; Bender, A.; Nigsch, F.; Patiny, L.;

Williams, A.; Tkachenko, V.; Tekto, I.V. Online chemical

modeling environment (OCHEM): web platform for data

storage, model development and publishing of chemical

information. Journal of computer-aided molecular design 2011,

25, 533-554, https://doi.org/10.1007/s10822-011-9440-2.

16. Aniceto, N.; Freitas, A.A.; Bender, A.; Ghafourian, T. A

novel applicability domain technique for mapping predictive

reliability across the chemical space of a QSAR: reliability-

density neighbourhood. Journal of Cheminformatics 2016, 8, 69,

https://doi.org/10.1186/s13321-016-0182-y.

17. Honda, H.; Minegawa, K.; Fujita, Y.; Yamaguchi, N.;

Oguma, Y.; Glatt, H.; Nishiyama, N.; Kasamatsu, T. Modified

Ames test using a strain expressing human sulfotransferase 1C2

to assess the mutagenicity of methyleugenol. Genes and

In silico toxicity prediction, synthesis, characterization, antimicrobial and antioxidant activity of different di substituted

chalcones

Page | 913

Environment 2016, 38, 1, https://doi.org/10.1186/s41021-016-

0028-x.

18. de Mello Silva Oliveira, N.; Reis Resende, M.; Alexandre

Morales, D.; de RagãoUmbuzeiro, G.; Boriollo, M.F.G. In vitro

mutagenicity assay (Ames test) and phytochemical

characterization of seeds oil of Helianthus annuusLinné

(sunflower). Toxicology reports 2016, 3, 733-739,

https://doi.org/10.1016/j.toxrep.2016.09.006.

19. Prival, M.J.; Zeiger, E. Chemicals mutagenic in Salmonella

typhimurium strain TA1535 but not in TA100. Mutation

research 1998, 412, 251-260, https://doi.org/10.1016/s1383-

5718(97)00196-4.

20. Daina, A.; Michielin, O.; Zoete, V. SwissADME: a free web

tool to evaluate pharmacokinetics, drug-likeness and medicinal

chemistry friendliness of small molecules. Scientific reports

2017, 7, 42717, https://doi.org/10.1038/srep42717.

21. Claxton, L.D.; UmbuzeiroGde, A.; DeMarini, D.M. The

Salmonella mutagenicity assay: the stethoscope of genetic

toxicology for the 21st century. Environmental health

perspectives 2010, 118, 1515-1522,

https://doi.org/10.1289/ehp.1002336.

22. Sashidhara, K.V.; Rosaiah, J.N.; Kumar, A. Iodine-Catalyzed

Mild and Efficient Method for the Synthesis of Chalcones.

Synthetic Communications 2009, 39, 2288-2296,

https://doi.org/10.1080/00397910802654724.

23. Mojžiš, J.; Sarisský, M.; Pilatova, M.; Voharová, V.;

Varinska, L.; Mojzisová, G.; Ostro, A.; Urdzik, P.; Dankovcik,

R.; Mirossay, L. In vitro antiproliferative and antiangiogenic

effects of Flavin7®. Physiological research / Academia

ScientiarumBohemoslovaca2008, 57, 413-420.

24. Kulathooran. S.; Dhamodaran, M. Synthesis And Biological

Evaluation Of Some New Chalcones Using Anhydrous

Potassium Carbonate As An Efficient Basic Catalyst By

Conventional And Microwave Assisted Techniques.Ijpsr2015,

47, 3027-33.

25. Braca, A.; De Tommasi, N.; Di Bari, L.; Pizza, C.; Politi, M.;

Morelli, I. Antioxidant principles from Bauhinia tarapotensis.

Journal of natural products 2001, 64, 892-895,

https://doi.org/10.1021/np0100845.

26. Khalil, N.S. Efficient synthesis of novel 1,2,4-triazole fused

acyclic and 21-28 membered macrocyclic and/or lariat

macrocyclicoxaazathia crown compounds with potential

antimicrobial activity. Eur J Med Chem2010, 45, 5265-5277,

https://doi.org/10.1016/j.ejmech.2010.08.046.

27. Dhorajiya, B.D.;Dholakiya, B.Z. Design, Synthesis and

Comparative Study of Anti-Microbial Activities on Barbituric

Acid and Thiobarbituric Acid based Chalcone Derivatives

Bearing the Pyrimidine Nucleus.ChemSci J2016,7, 1-9.

28. Opletalova, V.; Jahodar, L.; Jun, D.; Opletal, L. [Chalcones

(1,3-diarylpropen-1-ones) and their analogs as potential

therapeutic agents in cardiovascular system diseases]. Ceska a

Slovenskafarmacie :casopis Ceske farmaceutickespolecnosti a

Slovenskefarmaceutickespolecnosti2003, 52, 12-19.

29. Sambamoorthy, U.; Venkataraju, M.; Manjappa, A.; Rao, M.

Gemcitabine-loaded Folic Acid Tagged Liposomes: Improved

Pharmacokinetic and Biodistribution Profile. Current Drug

Delivery 2018, 15,

https://doi.org/10.2174/1567201815666181024112252.

30. Khan, S.A.; Asiri, A.M. Green synthesis, characterization

and biological evaluation of novel chalcones as anti bacterial

agents. Arabian Journal of Chemistry 2017, 10, S2890-S2895,

https://doi.org/10.1016/j.arabjc.2013.11.018.

31. Kurt, B.Z.; OztenKandas, N.; Dag, A.; Sonmez, F.;

Kucukislamoglu, M. Synthesis and biological evaluation of

novel coumarin-chalcone derivatives containing urea moiety as

potential anticancer agents. Arabian Journal of Chemistry 2020,

13, 1120-1129, https://doi.org/10.1016/j.arabjc.2017.10.001.

32. Seema, I.H. Chemical and biological potential of chalcones

as a source of drug.Ijppr2018, 11,104-118.

33. Baluja, S.; Vakariya, N.; Hirapara, A.Synthesis,

phytochemical studies of vanillin chalcones.

Scientific research2018, 47, 185-215,

http://dx.doi.org/10.15446/rcciquifa.v47n2.73966.

34. Deepika, P.; Maheswari, D.U.; Kumar, P.S.S.Chalcones as

Promising Antiproliferative Drug-A Review.Ijrsi2020, 7, 53.

35. Ardiansah, B. Chalcones bearing N, O, and S-heterocycles:

Recent notes on their biological significances. Journal of

Applied Pharmaceutical Science 2019, 9, 117-129,

https://doi.org/10.7324/JAPS.2019.90816.

36. Koudokpon, H.; Armstrong, N.; Dougnon, T.V.; Fah, L.;

Hounsa, E.; Bankole, H.S.; Loko, F.; Chabriere, E.; Rolain, J.M.

Antibacterial Activity of Chalcone and Dihydrochalcone

Compounds from Uvariachamae Roots against Multidrug-

Resistant Bacteria. BioMed research international 2018, 2018,

https://doi.org/10.1155/2018/1453173.

6. ACKNOWLEDGEMENTS

This research supported by Dr Y AnkammaChowdary, professor and principal of Nri College of pharmacy. We thank our

collegues who provide insight and expertise that greatly assisted the research.

© 2020 by the authors. This article is an open access article distributed under the terms and conditions of the

Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).