Reza Mohammadhassan, Sepideh Fallahi, Zahra Mohammadalipour

Page | 840

ADMET and pharmaceutical activity analysis of caffeic acid diversities by in silico tools

Reza Mohammadhassan 1, *

, Sepideh Fallahi 2

, Zahra Mohammadalipour 3

1 Plant Science Department, Amino Techno Gene Private Virtual Lab, Tehran, Iran 2Animal Science Department, Amino Techno Gene Private Virtual Lab, Tehran, Iran 3 Medical Science Department, Amino Techno Gene Private Virtual Lab, Tehran, Iran

*corresponding author e-mail address: rezarmhreza22@gmail.com ABSTRACT

Caffeic acid diversities are widely considered as one of the most pharmaceutical secondary metabolites to study for treating a wide range

of disorders and diseases. In this paper, toxicity, ADME, and pharmaceutical activity of 16 compounds of the Caffeic acid diversities, are

analyzed by Toxtree software and Molinspiration website, respectively. According to the results, it can be concluded that Caffeoylmalic

acid and Dactylifric acid could be considered as the safest and the most applicable compounds. It might be suggested that modification

of molecular structures of Chlorogenic acid and Neochlorogenic acid could be useful for becoming low toxic and more applicable

compounds for oral consumption.

Keywords: Caffeic acid diversities; ADME; Toxicity; pharmaceutical activity; Lipinski's rule of five; in silico.

1. INTRODUCTION

Medicinal plants contain effective ingredients that can

physiologically influence on other organisms. These ingredients,

known as secondary metabolites that are biosynthesized in low

amount, usually less than 1 percent of plant dried weight.

Generally, they are also low-molecular-weight compounds, less

than 150 KDa [1]. Secondary metabolites play remarkable

ecological roles in plants. The metabolites are widely used as bio-

herbicide, flavoring agents, natural colors and medication in

biotechnology [2]. Antioxidants, such as Flavonoids, are the most

remarkable metabolites [3]. Caffeic acid diversities are classified

as the most common and applicable Flavonoids that contain

phenolic and acrylic functional groups [4]. There can be found

caffeic acid diversities in many medicinal plants, such as

Echinacea (Echinacea purpurea) [5], tea (Camellia sinensis) [6]

and Eucalyptus (Eucalyptus globulus) [7]. Caffeic acid

biosynthesis is promoted by coumaroyl ester hydroxylating quinic

acid. Then, chlorogenic acid and caffeic acid ester are

consequently biosynthesized. The compounds are precursors of

other caffeic acid diversities biosynthesis [8].

These compounds have antibacterial, anti –mutagenic, and

antiviral effects. There are many studies to demonstrate medicinal

effects, particularly antiviral such as inhibiting replication of HIV

[5], hepatitis B virus (HBV) and hepatitis C virus as two fatal

factors to cause viral hepatitis [9]. Many studies have been

reported strong anti-oncologic activities of the compounds on

many types of cancer, particularly breast cancer [10], oral cancer

[11] and prostate cancer [12]. Caffeic acid diversities can also

elicit neuroprotective activity to prevent neurodegeneration [13]

especially in Parkinson as the intense and progressive movement

disorder, caused by the death of neurons in the brain [14].

In pharmacology and pharmacokinetics, ADMET

(Absorption, Distribution, Metabolism, Excretion, and Toxicity)

describes the condition of the pharmaceutic compounds within an

organism. All the four criteria and kinetic effect on the pharmaceutic activity and function of the candidate compound as a

medicine, consequently tissues [15]. Biological/pharmaceutical

activity describes the favorable and detrimental effects of the

candidate medicine on an organism. Among several characteristics

of each compound, bioactivity plays prominent roles to employ it

as a medication. Whilst, biochemical compounds probably show

some detrimental and toxic effects which perhaps prevent to be

applied in pharmacology [16]. Both bioactivity and ADMET can

be analyzed by Lipinski’s rule of five. This rule, also known as the

Pfizer's rule of five, is employed to investigate drug-likeness, as

well as determine the characteristics of the chemical compounds

with specific biological and pharmaceutical activity for feasible

oral consumption [17]. There can be found many studies about

analyzing ADMET and bioactivity of herbal compounds by

bioinformatic tools. Mekha Mohan et al. (2015) has analyzed

ADMET and pharmaceutical activity of phytochemicals which can

be extracted from Phyllanthus niruri [18]. Also, six alkaloids

including oliveroline, coptisine, aristolactam, and piperine, have

been evaluated for ADMET and biological activity factors by in

silico tools [19], as well as velutin, galugin, chrysin, and zileuton

[20]. Tiwari et al. (2018) have computationally analyzed

biological activity and ADMET of nineteen secondary metabolites

[21].

Constantinescu et al. (2019) were also reported in silico

study about ADMET and bioactivity of 44 previously

biosynthesized compounds such as thiazole chalcones, flavanones,

flavones, 3-hydroxyflavones, and their acetylated diversities [22].

In the study, ADMET and pharmaceutical activity of 16 diversities

of caffeic acid were analyzed by chemoinformatic tools.

2. MATERIALS AND METHODS

2.1. Data collecting. ChemSpider (http://www.chemspider.com/),

as a huge database for chemical compounds [23], was used to

collect the information of the caffeic acid diversities.

2.2. ADME analysis. ADME of these derivatives, was analyzed

by Molinspiration website (http://www.molinspiration.com/),

regarding chemical structure [23].

Volume 9, Issue 1, 2020, 840 - 848 ISSN 2284-6808

Open Access Journal Received: 15.01.2020 / Revised: 18.02.2020 / Accepted: 19.02.2020 / Published on-line: 21.02.2020

Original Research Article

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

https://doi.org/10.33263/LIANBS91.840848

ADMET and pharmaceutical activity analysis of caffeic acid diversities by in silico tools

Page | 841

2.3. Toxicity analysis. The toxicity of the compounds was

estimated by ToxTree software (http://toxtree.sourceforge.net).

This software compares an intended chemical substance with

detected and known toxic compounds [23].

2.4. Bioactivity analysis. Molinspiration website was also applied

for analyzing bioactivity of caffeic acid diversities [23].

3. RESULTS

Lipinski’s rule of five defines that, candidate compound for

an oral active medication must have no more than one violation of

these following criteria: 1. logP is no more than 4.15. 2. Molecular

weight is no more than 500. 3. It should have less than five donors

of the hydrogen bond 4. It should have less than ten acceptors of

the hydrogen bond. logP defines candidate oral drug suitability.

Lower molecular weight is considered for the ability of diffusion.

The amounts of the Hydrogen bond acceptors and donors can

determine water solubility [17]. For the analysis of the bioactivity,

a lower score than -5.0, between 0.0 and -5.0 and a higher score

than 0.0 respectively mean active, moderately active and inactive

[24]. It also seems that score between 2.0 and 4.0 is higher active

(blue range) and more than 4.0 means the highest active (green

range).

Table 1. Bioactivity and ADMET analysis of Caffeic acid.

AMDE

volume nviolations nOHNH nON Molecular Weight natoms TPSA miLogP

154.50 0 3 4 180.16 13 77.75 0.94

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase inhibitor Ion channel

modulator

GPCR

ligand

-0.09 -0.79 -0.10 -0.81 -0.23 -0.48

Table 2. Bioactivity and ADMET analysis of Ethyl caffeate.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

188.83 0 2 4 208.2 15 66.76 1.93

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

-0.22 -0.71 -0.18 -0.78 -0.29 -0.59

Table 3. Bioactivity and ADMET analysis of Methyl caffeate.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

172.03 0 2 4 194.1 14 66.76 1.56

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Prote

ase

inhibi

tor

Nuclear

receptor

ligand

Kinase inhibitor Ion channel

modulator

GPCR

ligand

-0.22 -0.78 -0.26 -0.82 -0.32 -0.62

3.1. Caffeic acid.

All these criteria for caffeic acid AMDE are in the proper

range, regarding the Lipinski’s rules of five. In other word, there is

no violation of Lipinski’s rule of five. Moreover, the toxic hazard

of the compound was estimated low; as well as classified I.

Enzyme inhibitor score (-0.09) is considered as the highest

biological activity of Caffeic acid (Table 1).

Reza Mohammadhassan, Sepideh Fallahi, Zahra Mohammadalipour

Page | 842

3.2. Ethyl caffeate.

There is no violation of the rule of five. Toxic hazard is

estimated low and also classified I. The highest score of

pharmaceutical activity belongs to enzyme inhabitation (-0.22)

(Table 2).

3.3. Methyl caffeate.

There cannot be found any violation of Lipinski’s rule of

five. Methyl caffeate was classified as a low toxic hazard

compound, class I. Enzyme inhabitation of this compound was

scored -0.22, as the highest biological activity (Table 3).

Many studies have demonstrated the pharmaceutical

activities of caffeic acid diversities. Antidiabetic effects of caffeic

acid are caused by the inhabitation of α-amylase and α-glycosidase

[25]. The compound can also suppress lipid accumulation by

inhabiting PPARγ protein expression [26]. Methyl caffeate can

induce apoptosis by activation of caspase [27], as well as reduce

low inflammation related to age which causes neurodegenerative

diseases [28] such as Parkinson [14]. Ethyl caffeate can

increasingly regulate caspase 3 and caspase 9 in tumor tissues [29]

and also inhibits immune response and signaling, related to

interferon γ, to cure arthritis, induced by collagen [30]. The

current results show that the above mentioned caffeic acid

diversities are proper for oral consumption with low toxic hazard.

But, against previous studies and the results, there are no desirable

biological activities for these compounds, regarding the present

analysis.

3.4. Echinacoside.

Topological polar surface area (TPSA), Molecular weight

(MW), Hydrogen bond donors and acceptors of Echinacea are

respectively 324.44, 786.73, 12 and 20. So, there can be found

three violations of the rule of five. Toxic hazard is also classified

high and class III. The highest bioactivity of the compound is the

estimated protease inhibitor (-0.88) (Table 4).

Table 4. Bioactivity and ADMET analysis of Echinacoside.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

664.6 3 12 20 786.7 55 324.4 -2.15

Toxicity

Toxic Hazard class Toxic Hazard

III High

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

-1.56 -0.88 -2.04 -1.99 -2.44 -1.28

Table 5. Bioactivity and ADMET analysis of Cynarine.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

431.08 3 7 12 516.4 37 211.2 1.42

Toxicity

Toxic Hazard class Toxic Hazard

III High

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.42 0.21 0.50 -0.01 0.04 0.18

3.5. Cynarine.

TPSA, MW, Hydrogen bond donor and acceptor scores

of Cynarine are respectively 211.2, 516.4, 12 and 7. So, there are

three violations of Lipinski’s rule of five. The toxic hazard is high

and classified III. Nuclear receptor, protease and enzyme

inhibitors were scored as the highest pharmaceutical activities, in

order to 0.50, 0.21 and 0.42 (Table 5).

3.6. p-Coumaric acid glucoside.

Although there is no violation of the rule, the toxic

hazard was categorized class III and high. Nuclear receptor ligand

and enzyme inhibitor are respectively estimated 0.30 and 0.42 as

the highest pharmaceutical activities of p-Coumaric acid glucoside

(Table 6).

3.7. Caftaric acid Conj.

AMDE Analysis of Caftaric acid Conj. (conjugated with

glutathione) shows 3 violation of the rule including TPSA (320.4),

MW (617.5), Hydrogen bond donors (18) and acceptors (11). The

hazard of the toxicity is high for the compound, consequently,

categorized in class III. Protease inhabitation reached just the

highest score of biological activity (Table 7).

ADMET and pharmaceutical activity analysis of caffeic acid diversities by in silico tools

Page | 843

All reported studies on Caftaric acid conj. are in the wine

production field, not pharmacology [31]. In the contrary, there are

many pharmacological studies for p-Coumaric acid glucoside,

Cynarine, and Echinacoside. p-Coumaric acid glucoside can

effect as same as dexamethasone on hypoxic cerebral edema [32];

as well as normobaric hypoxic pulmonary edema. So, the

compound could improve lung barrier [33] and blood-brain-barrier

and inhibit oxidative stress and, consequently, inflammation [32].

According to previous studies, Cynarine shows antioxidant,

antichlorogenic, antiradical [34] and antigenotoxic effects [35].

Echinacoside can effect as a neuroprotective compound against

neuroinflammation and signals related to Parkinson [36]. In other

words, this compound can protect neurons against apoptosis

induced by methyl-4-phenylpyridinium in the disorder [37]. The

present results could confirm the high pharmaceutical activity of

the above mentioned natural compounds, except Echinacoside,

particularly nuclear receptors ligands and inhabitation protease

and enzymes in blue level; but, just p-Coumaric acid glucoside is a

suitable compound for oral consumption, with regards to ADME

analysis. Nevertheless, all these compounds are highly toxic.

Table 6. Bioactivity and ADMET analysis of p-Coumaric acid glucoside.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

278.6 0 5 8 326.3 23 136.6 -0.36

Toxicity

Toxic Hazard class Toxic Hazard

III High

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.42 0.07 0.30 -0.12 -0.01 0.17

Table 7. Bioactivity and ADMET analysis of Caftaric acid Conj.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

498.19 3 11 18 617.5 42 320.4 -5.19

Toxicity

Toxic Hazard class Toxic Hazard

III High

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.18 0.38 -0.09 -0.32 -0.35 0.17

3.8. Chicoric acid.

Score of TPSA, Hydrogen donors and acceptors of

Chicoric acid are estimated 208.1, 12 and 6 respectively.

Consequently, just one violation of the rule of five could be found.

Besides, the toxic hazard of the compound was predicted as low;

as well as classified I. Nuclear receptor ligand (0.29) score shows

the highest bioactivities of the compound (Table 8).

3.9. Caftaric acid.

There can be found just one violation of the rule, caused by

score of TPSA (161.5). In addition, the toxic hazard of the

compound was predicted low and classified I. The highest

biological activities of the compound are nuclear receptor ligand

(0.41) and enzyme inhibitor (0.26) (Table 9).

3.10. Coutaric acid.

There are no violations of Lipinski’s rules of five for

Coutaric acid. The toxic hazard of the compounds was estimated

low, as well as class I. Nuclear receptor ligand (0.44) and enzyme

inhibitor (0.28), are considered as the highest biological activities

of this compound (Table 10).

3.11. Fertaric acid.

The violation of the rules was scored 0 for Fertaric acid.

The hazard of the toxicity is low and classified I. Nuclear receptor

ligand (0.34) was determined as the highest biological activity of

the compound (Table 11).

3.12. Caffeic acid phenethyl ester.

Violation of the rule of five was scored 0 for Caffeic acid

phenethyl ester. The compound was also estimated as a low toxic

hazard (class I). Nuclear receptor ligand (0.26) is considered as the

highest biological activity of this compound (Table 12).

There are some studies to report anti-inflammatory

properties of Fertaric acid [38]; as well as protecting liver against

4-tert-octylphenol caused by hepatotoxicity [39]. Many studies

Reza Mohammadhassan, Sepideh Fallahi, Zahra Mohammadalipour

Page | 844

have also demonstrated anticarcinogenic, anti-inflammatory,

immunomodulatory, antimutagenic and antiviral activities of

Caffeic acid phenethyl ester [40]. The compound can also inhibit

metabolic enzymes, specifically Acetylcholinesterase and

Butyrylcolinesterase [41]. Several studies have shown anti-

inflammatory and antioxidant properties of Caftaric acid in gastric

ulcer induced by indomethacin [42] and also antidiabetic and

antihypertensive effects [43]. There are many reports to the

indicated antiviral activity of Chicoric acid against herpes simplex

(HSV), influenza and human immunodeficiency viruses (HIV)

[44] and also can induce apoptosis to inhibit human breast cancer

cells [45]. There cannot be found any research on pharmaceutical

activity of Coutaric acid. According to the present results, Caffeic

acid phenethyl ester, Fertaric acid and Coutaric acid exert no

violation of the rule. So, these three compounds can be orally

consumed. In contrast, there are one and two violations of Caftaric

acid and Chicoric acid, respectively. Caffeic acid phenethyl ester

and Fertaric acid are biologically active to bind nuclear receptors.

Coutaric acid, Caftaric acid and Chicoric acid are also

pharmaceutical active for binding nuclear receptors and inhibiting

enzymes. Nevertheless, all these five caffeic acid diversities are

classified as low toxic compounds.

Table 8. Bioactivity and ADMET analysis of Chicoric acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

385.9 2 6 12 474.3 34 208.1 1.27

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.13 -0.03 0.29 -0.15 -0.06 0.05

Table 9. Bioactivity and ADMET analysis of Caftaric acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

251.14 1 5 9 312.2 22 161.5 -0.61

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.26 -0.05 0.41 -0.29 -0.12 0.04

Table 10. Bioactivity and ADMET analysis of Coutaric acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

243.12 0 4 8 296.2 21 141.3 -0.12

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.28 -0.06 0.44 -0.30 -0.10 0.03

ADMET and pharmaceutical activity analysis of caffeic acid diversities by in silico tools

Page | 845

Table 11. Bioactivity and ADMET analysis of Fertaric acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

268.67 0 4 9 326.2 23 150.5 -0.3

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.19 -0.10 0.34 -0.28 -0.19 0.00

Table 12. Bioactivity and ADMET analysis of Caffeic acid phenethyl ester.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

260.48 0 2 4 284.3 21 66.76 3.36

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.11 -0.08 0.26 -0.15 -0.04 0.01

3.13. Chlorogenic acid.

There can be found just a violation of the rule of five for

TPSA (164.7). Toxic Hazard was estimated as intermediate and

classified II. The compound is biologically active as GPCR ligand

(0.29), nuclear receptor ligand (0.74), protease (0.27) and enzyme

inhibitor (0.26) (Table 13).

3.14. Neochlorogenic acid.

Hydrogen acceptors of Neochlorogenic acid were

calculated 6 that it is considered as a violation of the rule. The

toxic hazard of the compound was estimated as intermediate, class

II. Enzyme inhibitor (0.74) and nuclear receptor ligand (0.62)

show the highest bioactivity of this compound; then GPCR ligand

(0.29) and protease inhibitor (0.27) (Table 14).

3.15. Caffeoylmalic acid.

There is no violation of the rule for Caffeoylmalic acid.

Toxic Hazard was classified I; as well as estimated low toxicity.

The highest bioactivity of the compound is found for nuclear

receptor ligand and enzyme inhibitor, 0.52 and 0.43 respectively

(Table 15).

3.16. Dactylifric acid.

There cannot be found any violation of the rule of five.

Toxic hazard was estimated intermediate and classified II. The

highest biological activities belong to the nuclear receptor ligand

(0.61) and enzyme inhibitor (0.52) (Table 16).

Table 13. Bioactivity and ADMET analysis of Chlorogenic acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

296.27 1 5 9 354.3 25 164.7 -0.45

Toxicity

Toxic Hazard class Toxic Hazard

II Intermediate

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.62 0.27 0.74 -0.00 0.14 0.29

Reza Mohammadhassan, Sepideh Fallahi, Zahra Mohammadalipour

Page | 846

Table 14. Bioactivity and ADMET analysis of Neochlorogenic acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

296.27 1 6 9 354.3 25 164.7 -0.45

Toxicity

Toxic Hazard class Toxic Hazard

II Intermediate

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.62 0.27 0.74 -0.00 0.14 0.29

Table 15. Bioactivity and ADMET analysis of Caffeoylmalic acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

243.10 0 4 8 296.2 21 141.3 0.31

Toxicity

Toxic Hazard class Toxic Hazard

I Low

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.43 0.16 0.52 -0.15 -0.01 0.19

Table 16. Bioactivity and ADMET analysis of Dactylifric acid.

AMDE

volume nviolations nOHNH nON MW natoms TPSA miLogP

282.36 0 5 8 336.3 24 144.5 0.31

Toxicity

Toxic Hazard class Toxic Hazard

II Intermediate

Biological activity

2D Structure Enzyme

inhibitor

Protease

inhibitor

Nuclear

receptor

ligand

Kinase

inhibitor

Ion channel

modulator

GPCR

ligand

0.52 0.15 0.61 -0.14 0.18 0.15

There could not be found any pharmacological studies on

Caffeoylmalic acid and Dactylifric acid. But according to the

results, Caffeoylmalic acid is low toxic and high bioactive

compounds, especially as more highly activity to bind nuclear

receptors and most enzyme inhibitory. Dactylifric acid also exerts

moderate toxicity and green range activity for both binding

nuclear receptors and inhibiting enzymes. Many studies have

demonstrated the antidiabetic effects of Chlorogenic acid by

inhibiting α-amylase and α-glycosidase [25]. The compound can

activate caspase to induce apoptosis in human renal cell carcinoma

[46] and also inhibit reverse transcriptase activity of HIV-1 [47].

Other studies reported the antioxidant activity of

Neochlorogenic acid. It can also inhibit α-glycosidase [48] and the

activity of the influenza virus [49]. Moreover, the compound

exerts neuroprotective effects by inhibiting the pathway of pro-

inflammation in activated microglia cells [50]. The present results

demonstrated the same properties for both Chlorogenic acid and

Neochlorogenic acid. They are classified as intermediate toxic

compounds, with just one violation of the rule of five, caused by

six hydrogen binding acceptors. Nevertheless, they are highly

pharmaceutically active, particularly binding.

4. CONCLUSIONS

Conclusively, Caffeoylmalic acid and Dactylifric acid are

the safest and the most applicable compounds between all sixteen

analyzed caffeic acid diversities, although there are not any studies

to report the pharmaceutical activity of Caffeoylmalic acid and

Dactylifric acid. Moreover, Chlorogenic acid and Neochlorogenic

acid, with the same characteristics can be considered as two potent

ADMET and pharmaceutical activity analysis of caffeic acid diversities by in silico tools

Page | 847

drug due to their high bioactivity. But their moderate toxicity and

a violation of the rule maybe play a role as the restriction factors

for becoming a potent drug. It can be expected to modify

molecular structures of both compounds to decrease the toxicity

level and the violation.

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