Article  
Molecular Docking Study of Chalcone Analogue Compounds with Hydroxy and  
Methoxy Subtituents as Bcl-2 Inhibitors  
Neni Frimayanti1*, Rahma Dona1, Tabah Solihin1  
1Department of Pharmacy, Faculty of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Pekanbaru 28928,  
Riau, Indonesia  
Abstract  
Molecular docking study of 6 chalcone analogues with protein target from the crystallographic structure  
modeling of Bcl-2 protein with PDB code 2W3L was carried out using computational media using the  
Molecular Operating Environment (MOE) program. The aim of this study is to determine the potentiality  
of the 6 chalcone analogue compounds as Bcl-2 inhibitors using molecular docking studies. In this study,  
venetoclax was used as positive control. Based on docking results, binding free energy was used as  
information to know which wheather chalcone analogue compounds are active or not as Bcl-2 inhibitors.  
According to the docking results that have been carried out, it showed that the 6 chalcone analogue  
compounds have no potential as Bcl-2 inhibitors. Due to the superimposition of the 6 compounds that  
did not stick to the positive control and most importantly the binding free energy values (S) of the 6  
chalcone analogue compounds were higher than the binding free energy values of the positive control  
(Venetoclax).  
Keywords: chalcone analogue compound, molecular docking, venetoclax , Bcl-2 inhibitors  
Graphical Abstract  
*
Corresponding author  
Email addresses: nenifrimayanti@gmail.com  
DOI: 10.22437/chp.v7i1.17487  
Received 16 March 2022; Accepted 12 May 2023; Available online 30 July 2023  
Copyright © 2023 by Authors, Published by Chempublish Journal. This is an open access article under the CC BY License  
(https://creativecommons.org/licenses/by/4.0)  
31  
Chempublish Journal, 7(1) 2023, 31-41  
al.[7], and Oktaviani et al.[8]) who has conducted  
research for anticancer tests using the in-silico  
method.  
Introduction  
Cancer is a group of diseases characterized by  
uncontrolled cell division and the ability of these  
cells to invade other biological tissues, either by  
direct growth in adjacent tissues (invasion) or by  
migration to a more distant place distant  
(metastatic) [1]. Cancer or well known as a  
malignant tumor is abnormality genetic cause  
change function or expression of genes that  
regulate cellular processes like growth, survival  
life and aging. Damage genetics can caused by  
materials chemical, radiation , agent microbe or  
Kalkon is compound precursor from class of  
flavonoids and is intermediates important in  
synthesis organic, like compound heterocyclic  
(flavones, flavanols, flavanons). Chalcone has  
been widely developed and synthesized to obtain  
its derivatives and to test its pharmacological  
activity. Besides being caused by the presence of  
unsaturated α β groups, the bioactivity of  
chalcone compounds is also influenced by the  
substituents attached to the two aromatic rings  
[9]. The substituents present in the two aromatic  
rings of the chalcone greatly affect the activity of  
the chalcone compound, such as the presence of  
a methoxy group in ring A affecting the  
anticancer activity [10]. Suwito et al.[11] compared  
the effect of the methoxy position on the B ring  
at positions C2, C3, and C4 on the activity of  
chalcone as an anticancer. This study showed  
that the methoxy group was most active as an  
anticancer at the C4 position. In the studies by  
Mai et al. , and Anwar et al.[12] the presence of a  
hydroxy group in ring A also shows potential  
activity as an anticancer agent.  
Possible inherited (mutation germline) [2]  
.
Breast cancer is one of the most common types  
of cancer suffered by the world's population.  
Based on dat a Global Cancer Observatory  
[3]  
from World Health Organization (WHO) points  
out case new cancer highest in the world i.e.  
cancer breast as many as 2.261.419 case new  
(11.7%) and 684.996 case death (6.95%). Case  
numbers of new cancer boobs in Asia i.e.  
1.026.171 (10.8%), with case death 346.009  
(6.0%). In Indonesia, there were 65.858 new cases  
of breast cancer (16.6%) and 22.430 (9.6%) cases  
of death [3]  
.
Breast cancer is a group of diseases in which cells  
in the breast tissue change and divide in an  
uncontrolled manner, usually resulting in a lump  
or mass. Various kinds of cancer treatment have  
been carried out including surgery, radiation, use  
of anticancer drugs or chemotherapy. However,  
all these efforts have not yielded satisfactory  
results, and even the effects of failure of therapy  
and surgery have caused cancer cells to spread  
In a study of Oktaviani et al. in 2019 it was stated  
that the chalcone compound is  
a
strong  
candidate as a compound with great potential to  
be used as an anticancer drug [8]. One approach  
to the activity of chalcone compounds can be  
done with computational chemistry such as  
molecular docking. molecular docking is one of  
the computational methods used as a structure-  
based new drug discovery that measures the  
bond free energy between small molecules  
(ligands) and macromolecular targets (proteins)  
to other parts of the body [4]  
.
In the treatment of breast cancer drug therapy is  
very expensive, so people prefer to use  
traditional medicine. This is because traditional  
medicine has low side effects. In addition to these  
conventional treatments , the community has  
also tried many alternative treatments using  
natural ingredients (natural medicines) obtained  
from nature [5]. One of the compounds derived  
from plants and has anticancer properties is the  
chalcone compound , this is reinforced by  
previous studies (Pratoko et al.[6], Mahapatra, et  
[13]  
.
Molecular Docking can be used to predict  
whether a compound is active or not, such as  
chalcone  
derivatives.  
There  
are  
several  
advantages of the molecular method this  
docking, in between it is able to reduce the use of  
excessive tools and materials as well as save in  
financing, molecular docking can also be used to  
predict the activity of a compound that will  
interact with the active site of a protein [14]  
.
32  
Chempublish Journal, 7(1) 2023, 31-41  
Observation of molecular data results docking  
among them are the bond free energy involved  
in the process of ligand interaction with the  
receptor, the RMSD value, as well as the chemical  
bonds that are formed such as hydrogen bonds,  
van der Waals bonds, and bond hydrophobic  
using venetoclax as a positive control in docking  
simulations. In this study, a follow-up study was  
conducted on 6 chalcone analogues to determine  
the compound with the best bioactivity as a Bcl-2  
inhibitor using in silico studies, namely molecular  
docking. The purpose of this study was to  
determine whether 6 chalcone analogues have  
potential as Bcl-2 inhibitors in T47D breast cancer  
cells.  
[15,16]  
.
In breast cancer patients, Bcl2 levels have  
increased, Bcl-2 is a family of anti-apoptotic  
agents, this causes cells to not undergo the  
process of apoptosis. One of the drugs used in  
breast cancer chemotherapy is venetoclax. In  
breast cancer therapy venetoclax is used as a  
combination of cancer drugs in breast cancer  
Experimental Section  
Materials  
The materials used in molecular docking consists  
of a 2W3L target protein structure with PDB  
format. The ligand structures used are 6 chalcone  
therapy, venetoclax is  
a
drug that works  
selectively by inhibiting Bcl-2 target protein by  
inhibiting Bcl-2 so that the apoptosis process can  
take place and the number of cancer cells can be  
reduced [17,18], this is a reference for authors  
analogue  
compounds  
that  
have  
been  
synthesized by Prieto-Martinez et al.[19] and  
venetoclax as a positive control (Table 1).  
Tabel 1. Structure of 6 chalcone analogues and positive control (Venetoclax).  
Code  
MC 7  
Structure  
Code  
Structure  
MC 10  
(E)-1-(2-hydroxyphenyl)-3-(3-  
hydroxyphenyl) prop-2-en-1-one  
(E)-3-(3, 4-dimethoxyphenyl)-1-(2-  
hydroxyphenyl) prop-2-en-1-one  
MC 8  
MC 11  
(E)-1-(2-hydroxyphenyl)-3-(4-  
hydroxyphenyl) prop-2-en-1-one  
(E)-1-(2-hydroxyphenyl)-3-(3,4,5-  
trimethoxyphenyl)prop-2-en-1-one  
MC 9  
MC 12  
(E)-3-(benzo[d][1,3]dioxol-5-yl)-1-(2-  
hydroxyphenyl)prop-2-en-1-one  
(E)-1-(2-hydroxyphenyl)-3-(4-  
methoxyphenyl) prop-2-en-1-one  
33  
Chempublish Journal, 7(1) 2023, 31-41  
MA 7  
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazine-1-yl]-N-[3-nitro-4-  
(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridine-5-yloxy)benzamide  
[20]  
the better the pose of the ligand  
and for the  
Instrumentation  
RMSD value, the smallest value of RMSD will be  
taken with a value limit of ≤ 2 Å, according to  
Prieto-Martínez et al.[19]. The docking method is  
said to be valid if it has an RMSD value of ≤ 2 Å.  
The RMSD value indicates that the deviation or  
error value occurs when docking. The smaller the  
RMSD value, the smaller the deviation or error  
that occurs when docking.  
The tools used in this study consisted of  
computer hardware LG Intel (R) Core (TM) i7-8700  
CPU, 3.20 GHz, with 16.0 GB of RAM. The software  
used on the computer is the Chemdraw  
Professional 15.0 program and the Molecular  
program Operating Environment (MOE) 2020.  
(Chemical Computing Group). All programs run  
with Operating System Windows 10 Pro 64 bit.  
In addition, another parameter that must be  
considered is the bond free energy which is the  
energy required by a ligand to bind to its protein  
(receptor). The smaller the bond free energy  
value, the more difficult the interaction between  
the ligand and the protein can be released. This  
indicates that the ligand-protein complex is  
Procedure  
Draw all the ligands on the chemdraw software  
after that it was copied to MOE and stored as a  
ligand database, the protein was downloaded  
and prepared on DSV and MOE software. After  
that, docking was done using MOE. Data analysis  
from molecular docking is based on energy free  
bond (S, kcal/mol) and RMSD values obtained  
from docking results are displayed in tabular  
form, image results are displayed in 2D and 3D.  
Then, the interaction between the ligand and the  
amino acids in the target protein was analyzed to  
determine the suitability of the amino acid to the  
venetoclax (positive control) and to observe the  
types of interactions that occur between the  
ligand and the receptor, such as hydrogen bonds,  
van der Waals bonds, and hydrophobic bonds.  
increasingly stable [21]  
.
Hydrogen bonds are also considered because in  
general the molecular interactions that occur in  
the body are in the form of non-covalent  
interactions because non-covalent interactions  
help stabilize the macromolecular structure in  
cells. Hydrogen bonds are non-covalent bonds.  
Non-covalent interactions are interactions that  
are formed from the sharing of two electrons by  
two atoms. Hydrogen bonds involve the  
interaction of positively charged hydrogen atoms  
with electronegative atoms such as Flour (F),  
Nitrogen (N), and Oxygen (O) [22]. In addition,  
hydrogen bonds can also be formed between the  
H atom and the phenyl ring present in a drug  
Results and Discussions  
The resulting porous ceramics  
Docking results can be seen in Table. 2, for the  
bond-free energy value, the smaller the value,  
compound [23]  
.
34  
Chempublish Journal, 7(1) 2023, 31-41  
Tabel 2. Docking results of chalcone analogues to the Bcl-2 target protein.  
Parameter  
Code  
No Compound  
Bond Free  
Energy  
(kcal/mol)  
Interaction  
van der  
Waals  
Similarity  
Amino  
acid  
Bond  
H
Interaction Interaction  
RMSD  
Test  
Other  
Hydrophobic  
1
Venetoclax  
(Control  
Positive)  
-8.9474  
1.4288 ARG26,  
TYR67  
GLU119,  
ASP62,  
GLU58  
SER75,  
PRO163,  
LEU160,  
SER76,  
TYR161,  
ALA59,  
ALA72,  
GLY104,  
PHE63,  
PHE71,  
SER64  
LYS22,  
ARG66,  
ARG65  
ARG68,  
ARG69  
-
2
MC7  
-4.7534  
1.4349 ARG66  
ASP61,  
GLU119  
VAL115,  
VAL118,  
SER75,  
TYR67,  
SER64  
ARG26,  
ARG65,  
LYS22,  
ARG68  
9
3
4
MC8  
MC9  
-4.7707  
-4.6253  
1.5923 ARG68,  
ASP61  
VAL118,  
VAL115,  
SER75,  
SER64  
VAL118,  
SER64,  
TYR67,  
VAL115,  
SER75,  
ASN122  
SER64,  
ASN122  
ARG66,  
LYS22,  
ARG65,  
ARG26  
ARG65,  
ARG66,  
ARG26  
7
7
TYR67  
1.5738 ARG68  
GLU119,  
ASP61  
5
6
MC10  
MC11  
-4.7726  
-5.1537  
1.5402 ARG66,  
ASP61,  
ASP62  
LYS22, ARG65  
6
ARG26  
1.3197  
-
ASP62,  
GLU119  
PHE63 ,  
VAL107,  
ALA59,  
VAL115,  
VAL118,  
PHE71,  
ALA72,  
SER75,  
ARG68,  
ARG26,  
ARG66  
12  
GLY104,  
TYR161  
Van der Waals bonds and hydrophobic bonds are  
also considered as supporting parameters to  
determine the stability of the ligand to the  
receptor so that a compound can be identified as  
having potential as an inhibitor for a type of  
disease.  
35  
Chempublish Journal, 7(1) 2023, 31-41  
In this study venetoclax was used as a positive  
control in the docking process. Venetoclax has  
another name Venclexta and has a tablet dosage  
form. In the treatment of breast cancer,  
ligands and other bonds are formed on the  
amino acid residues Ser-75, Pro-163, Leu-160,  
Ser-76, Tyr-161, Ala-59, Ala-72, Gly-104, Phe-63,  
Phe-71, Ser-64. This data shows the similarity of  
amino acids in other studies which have tested  
active in 2W3L proteins where the residues of the  
venetoclax is combined with tamoxifen (20 mg)  
[24]  
and venetoclax (200-800 mg) per day  
The  
mechanism of action of venetoclax is that it  
works by inhibiting Bcl-2. Venetoclax works by  
inhibiting anti-apoptotic Bcl-2 protein by binding  
same amino acids are Tyr-67, Phe-63, Phe-71 [25]  
.
Based on the results of the docking of the MC7  
compound (Figure 1), the bond free energy value  
was -4.7534 kcal/mol and the RMSD value was  
1.4349. In these data compound 1 (MC7) has the  
same interaction of 9 amino acid residues with  
the positive control (Venetoclax), where the  
hydrogen bonds in MC7 are formed at the Arg-66  
amino acid residue, while in the positive control  
the hydrogen bonds are formed at the Arg-26  
and Tyr-67 amino acid residues so that this  
compound does not have the same hydrogen  
bonds with the positive control. In the van der  
Waals bond, the MC7 compound has one thing in  
common with positive control, namely the Glu-  
119 amino acid residue. The bond free energy  
produced by MC7 is higher than the positive  
control, this too large difference in bond free  
energy causes the MC7 compound to be difficult  
to bind to the active site of the receptor. Based  
on this, the MC7 compound cannot be  
categorized as a compound that has the potential  
to act as a Bcl-2 inhibitor. Visualization of  
compound bonds with proteins as shown in  
Figure 2.  
to  
anti-apoptotic  
Bcl-2  
protein  
thereby  
preventing anti-apoptotic Bcl-2 protein from  
binding to BAX/BAK which is a family of pro-  
apoptotic Bcl-2 proteins. With the binding of anti-  
apoptotic Bcl-2 by venetoclax, BAX/BAK can  
activate the cell death process by releasing  
cytochrome c from mitochondria and activating  
caspase [25]. The structure of venetoclax has no  
similarity to the 2W3L protein-inherent ligand, so  
the docking process was carried out using the  
blind docking method. Blind docking is a docking  
method that does not determine the active site  
on the 2W3L protein [26]  
.
Docking results from venetoclax showed that  
venetoclax has a bond free energy of -8.9474  
kcal/mol and RMSD value of 1.4288. The  
hydrogen bonds that are formed are found in the  
amino acid residues Arg-26, Tyr-67. Van der  
Waals bonds are formed with the amino acid  
residues Glu-119, Asp-62, Glu-58. Hydrophobic  
bonds are formed at the amino acid residues Lys-  
22,  
Arg-66,  
Arg-65,  
Arg-68,  
Arg-69.  
The  
interactions that occur through bonds between  
Figure 1. Visualization Results of MC7 Compound Superimposition (Yellow) and Positive Control (Green).  
36  
Chempublish Journal, 7(1) 2023, 31-41  
(a)  
(b)  
Figure 2. Visualization molecular docking of (a) compound 1 (MC7) and (b) compound 2 (MC8).  
The docking results of compound 2 (MC8) on the  
target protein (2W3L) showed that the compound  
had a binding free energy value (kcal/mol) of -  
4.7707 and an RMSD value of 1.5923 (Figure 3).  
Compound 2 (MC8) has the same interaction of 7  
amino acid residues with the positive control  
(Venetoclax). In the van der Waals bond,  
compound 2 (MC8) does not have the same  
amino acid as the positive control. The hydrogen  
bonds formed in MC8 have 1 amino acid in  
common with the positive control, namely the  
Tyr-67 amino acid residue, in this case Tyr-67 acts  
as an acceptor for hydrogen bonds with hydroxy  
groups but the bond free energy that is formed  
at MC8 is higher than the positive control so that  
the bond energy that is formed is unstable at the  
Bcl-2 receptor [26]. From these results it is  
estimated that the MC8 compound is not active  
against Bcl-2 receptors.  
The docking results of compound 3 (MC9) on the  
target protein (2W3L) showed that the compound  
had a bond free energy value (kcal/mol) of -  
4.6253 and an RMSD value of 1.5738 (Figure 4).  
Compound 3 (MC9) has the same interaction of 7  
amino acid residues with the positive control  
(Venetoclax). The hydrogen bonds formed in  
MC9 have nothing in common with the positive  
control. The van der Waals bond formed in MC9  
has 1 amino acid in common, namely the Glu-119  
amino acid residue.  
Figure 3. Visualization Results of MC8 Compound Superimposition (Red) and Positive Control (Green).  
37  
Chempublish Journal, 7(1) 2023, 31-41  
Figure 4. Visualization Results of MC9 Compound Superimposition (Purple) and Positive Control (Green).  
Figure 5. Visualization Results of MC10 Compound Superimposition (Dark purple) and Positive Control  
(Green).  
The bond free energy formed at MC9 is higher  
than the positive control so that the bond energy  
formed is unstable at the Bcl-2 receptor. From  
these results it is estimated that the MC9  
compound is not active against the Bcl-2  
receptor.  
where the ketone group acts as an acceptor as  
can be seen in the 2D view in Figure 5.  
The bond free energy formed in MC10 does not  
approach the bond free energy value of the  
positive control so that the stability of the MC10  
bond is different from that of the positive control  
on the Bcl-2 receptor. From these results it is  
estimated that the MC10 compound is not active  
against Bcl-2 receptors.  
The docking results of compound 4 (MC10) in the  
face of the target protein (2W3L) showed that the  
compound had a bond free energy value  
(kcal/mol) of -4.7726 and an RMSD value of  
1.5402. Compound 4 (MC10) has the same  
interaction of 6 amino acid residues to the  
positive control (Venetoclax). The van der Waals  
bond formed in MC10 has 1 amino acid similarity,  
namely the Asp-62 amino acid residue. In terms  
of the hydrogen bonds, the MC10 compound has  
1 amino acid in common with the positive  
control, namely the Arg-26 amino acid residue,  
The docking results of compound 5 (MC11) on the  
target protein (2W3L) showed that the compound  
had a bond free energy value (kcal/mol) of -  
5.1537 and an RMSD value of 1.3197 (Figure 6).  
Compound 5 (MC11) has the same interaction of  
12 amino acid residues with the positive control  
(Venetoclax). Hydrogen bonds are not formed in  
MC11 so they don't have the same amino acids.  
38  
Chempublish Journal, 7(1) 2023, 31-41  
Figure 6. Visualization Results of Superimposition of MC11 Compounds (Brown) and Positive Control  
(Green).  
Figure 7. Visualization Results of Superimposition of MC12 Compounds (Sky Blue) and Positive Control  
(Green).  
The van der Waals bond formed in MC11 has 2  
amino acids in common, namely the Glu-119 and  
Asp-62 amino acid residues. The bond free  
energy formed at MC11 is higher than the  
positive control so that the bond energy formed  
is unstable at the Bcl-2 receptor. From these  
results it is estimated that the MC11 compound  
is not active against the Bcl-2 receptor.  
namely the Asp-62 amino acid residue. The bond  
free energy formed at MC12 is higher than the  
positive control so that the bond energy formed  
is unstable at the Bcl-2 receptor. From these  
results it is estimated that the MC12 compound  
is not active against the Bcl-2 receptor.  
Based on the docking results, compound 5  
(MC11) has the smallest bond free energy value  
of -5.1537 kcal/mol and an RMSD value of 1.3197.  
However, this compound does not form  
hydrogen bonds and only has 2 similar amino  
acid residues in the van der Waals bond,  
compound 5 (MC11) has the highest similarity of  
amino acid residues, namely 12 amino acids with  
positive control. Compound 4 (MC10) has a bond  
free energy value (kcal/mol) of -4.7726 and an  
RMSD value of 1.5402. The MC10 compound has  
1 similar amino acid residue in the hydrogen  
The docking results of compound 6 (MC12) on the  
target protein (2W3L) showed that the compound  
had a bond free energy value (kcal/mol) of -  
4.6939 and an RMSD value of 1.5137 (Figure 7).  
Compound 6 (MC12) has the same interaction of  
8 amino acid residues with the positive control  
(Venetoclax). The hydrogen bonds formed in  
MC12 do not have the same amino acid residues  
as the positive control. The van der Waals bond  
formed on MC12 has 1 amino acid in common,  
39  
Chempublish Journal, 7(1) 2023, 31-41  
5. Djajanegara, I.,  
&
Wahyudi, P. (2010). Uji  
bond and the ven der Waals bond also has 1  
similar amino acid residue, the same amino acid  
residue that compound 4 (MC10) has, namely 6  
amino acid residues with positive control.  
However, this compound has a high bond free  
energy compared to the positive control, making  
it difficult for the test compound to bind to the  
active site of the Bcl-2 protein.  
sitotoksisitas ekstrak etanol herba Ceplukan  
(Physalis angulata Linn.) terhadap sel T47D secara  
in vitro. Urnal Ilmu Kefarmasian Indonesia, 8(1), 41–  
47.  
6. Pratoko, D. K. (2012). Molecular Docking Turunan  
Kalkon Terhadap Reseptor Estrogen B (ER-B)  
Sebagai Antikanker Payudara. Jurnal Kimia Terapan  
Indonesia, 14(1), 20–25.  
Next, superimposition of 6 chalcone analogues  
was carried out. Superimposition was performed  
using the BIOVIA Discovery Studio Visualizer  
(DSV). Superimposition is used to determine the  
common features of all compounds, which may  
play a role in stabilizing the interaction between  
the ligand and the target protein. Based on the  
superimposition analysis of the 6 chalcone  
analogues, none of them attached to the positive  
control, so it can be concluded that none of the 6  
chalcone analogues were active on the Bcl-2  
target protein.  
7. Mahapatra, D. K., Bharti, S. K., & Asati, V. (2015).  
Anti-cancer chalcones: Structural and molecular  
target perspectives. European Journal of Medicinal  
Chemistry,  
98,  
69–114.  
https://doi.org/10.1016/j.ejmech.2015.05.004  
8. Oktaviani, R., Arifian, H., Rahmadani, A.,  
Zamruddin, N. M., & Rusli, R. (2019). Kajian In Silico  
Senyawa Turunan Kalkon sebagai Antikanker.  
Proceeding  
Conferences,  
of  
Mulawarman  
Pharmaceuticals  
9,  
22–26.  
https://doi.org/10.25026/mpc.v9i1.309  
9. Mohamed, M. F., Mohamed, M. S., Shouman, S. A.,  
Fathi, M. M., & Abdelhamid, I. A. (2012). Synthesis  
and Biological Evaluation of a Novel Series of  
Chalcones Incorporated Pyrazole Moiety as  
Anticancer and Antimicrobial Agents. Applied  
Biochemistry and Biotechnology, 168(5), 1153–1162.  
https://doi.org/10.1007/s12010-012-9848-8  
Conclusions  
Based on the research results, it is known that  
the docking results of 6 chalcone analogues with  
the codes MC7, MC8, MC9, MC10, MC11, and  
MC12 are not expected to have potential as Bcl-2  
inhibitors. This is due to the superimposition of  
the 6 compounds that do not stick to the positive  
control, but it is also due to the bond free energy  
10. Dona, R., Zamri, A., & Jasril, -. (2015). Sintesis Dan  
Uji  
Tersubstitusi Metoksi. Photon: Jurnal Sain Dan  
Kesehatan, 5(2), 9–14.  
https://doi.org/10.37859/jp.v5i2.579  
Toksisitas  
Senyawa  
Analog  
Kalkon  
(S) values of the  
6
chalcone analogous  
11. Suwito, H., Jumina, Mustofa, Ni’matuzahroh, &  
Puspaningsih, N. N. T. (2015). Anticancer and  
antimicrobial activity of methoxy amino chalcone  
derivatives. Der Pharma Chemica, 7(3), 89–94.  
compounds which are higher when compared to  
the bond free energy values of the positive  
control (Venetoclax).  
12. Anwar, C., Prasetyo, Y. D., Matsjeh, S., Haryadi, W.,  
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