Drug and Chemical Toxicology

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In silico evaluation of multispecies toxicity of

natural compounds

Sripriya N., Ranjith Kumar M., Ashwin Karthick N., Bhuvaneswari S. & Udaya
Prakash N. K.

To cite this article: Sripriya N., Ranjith Kumar M., Ashwin Karthick N., Bhuvaneswari S. & Udaya
Prakash N. K. (2019): In�silico evaluation of multispecies toxicity of natural compounds, Drug and
Chemical Toxicology, DOI: 10.1080/01480545.2019.1614023

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DRUG AND CHEMICAL TOXICOLOGY
https://doi.org/10.1080/01480545.2019.1614023

RESEARCH ARTICLE

In silico evaluation of multispecies toxicity of natural compounds

Sripriya N.a, Ranjith Kumar M.a, Ashwin Karthick N.a, Bhuvaneswari S.b and Udaya Prakash N. K.c
a
R and D, Marina Labs, Chennai, India; bDepartment of Botany, Bharathi Women’s College, Chennai, India; cDepartment of Biotechnology,
Vels Institute of Science, Technology and Advanced Studies, Chennai, India

ABSTRACT ARTICLE HISTORY

Natural compounds are widely explored in industries, as a lead compound. Evaluating their toxicity is Received 14 January 2019
of utmost importance, as they may cause other side effects. The major hassles in evaluating the toxicity Revised 20 April 2019
of compounds through in vivo and in vitro methods such as time, money, workforce, and use of animal Accepted 25 April 2019
models can be overcome by computational methods. Quantitative structure–activity relationship
KEYWORDS
(QSAR) models predict the toxicity from the structure of a compound. In the present study, the metha- Natural compounds; GC-MS;
nolic extracts of three plants, namely, Carissa carandas, Canthium angustifolium, and Epiphyllum oxype- QSAR; TEST; toxicity
talum, were subjected to Gas Chromatography-Mass Spectrometry (GC-MS), in which 27 different
compounds were identified. The compounds were evaluated for their toxicity through QSAR-Toxicity
Estimation Software Tool (TEST) against multispecies – Daphnia magna, Pimephales promelas,
Tetrahymena pyriformis, and rat (Oral). The study revealed that the order of toxicity of the natural com-
pounds was D. magna > T. pyriformis > P. promelas > Rat (Oral). All the compounds were non-bioac-
cummulative, while most of them were developmental toxicants. Only one compound (Dasycarpidan-1-
methanol, acetate (ester)) was a mutagen. Further studies of the compounds on in vivo models are rec-
ommended after in silico analysis, for exploration in different industries.

Introduction physiochemical properties of the compound (Barratt 2000).

Quantitative structure activity relationships (QSARs) are math-
Plant and plant products have revolutionized the modern
ematical models used for predicting structure relative activ-
world with a market size of 62 billion dollars. Most of the
ities of the compound (Kar and Roy 2010).
countries use medicinal plants in therapeutics for cardiovas-
Toxicity of various compounds such as phenols
cular diseases, inflammation disorders and cancer. Industries
(Duchowicz et al. 2008), pesticides (Basant et al. 2015), food
isolate the active components of medicinal plants to utilize
chemicals (Valerio et al. 2007), industrial chemicals (Alves
in their product formulation. In food and cosmetic industries,
et al. 2018), narcotic chemicals (Aruoja et al. 2014), and
plants are used for their antioxidant and antimicrobial prop-
organic chemicals (Singh et al. 2014) have been predicted
erties. Further, pharmacological industries utilize medicinal
using QSAR models previously. However, studies on toxicity
plants as an agent for drug synthesis. However, safety and
of natural compounds from plants are scarce. In the present
efficacy are the major factors that hinder the utilization of
study, three plants, namely, Canthium angustifolium, Carissa
plants before they reach the market (Harrison 2016).
carandas, and Epiphyllum oxypetalum, are subjected to GC-MS
Transformation of plant compounds to the development of
analysis and further evaluated for their toxicity through the
drugs or other finished products necessarily requires know-
in silico method.
ledge on the toxicity of the compounds. About one-third of
the products developed fail due to preclinical toxicity and
adverse drug reactions (Hornberg et al. 2014). The major has- Materials and methods
sles in evaluating the toxicity of compounds through in vivo
Weed collection, extraction, and GC-MS analysis
and in vitro methods are time, money and workforce (Lei
et al. 2017). Toxicity assessment through computational The leaves of Canthium angustifolium (Rubiaceae), Carissa car-
methods provides knowledge on chemicals lacking experi- andas (Apocynaceae), and Epiphyllum oxypetalum (Cactaceae)
mental data and aids in screening of chemicals for early drug were collected from Tiruvananthapuram of Kerala state in
development (Jordan et al. 2010). Additionally, these meth- India. The collected healthy leaves were dried under shade,
ods serve as an alternate to toxicity studies on animal mod- pulverized, and extracted with methanol at a ratio of 1:10
els. In silico prediction methods determine the activity of a (w/v) by cold percolation method. The methanolic extract
chemical in any given biological system based on the was analyzed by Gas Chromatography-Mass spectrometry

CONTACT Udaya Prakash N. K. nkudayaprakash@gmail.com Department of Biotechnology, School of Life Sciences, Vels Institute of Science, Technology
and Advanced Studies, Pallavaram, Chennai, India
Supplemental data for this article can be accessed here.
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 SRIPRIYA N. ET AL.
Figure 1. GC-MS spectrum of (a) C. angustifolium, (b) C. carandas, and (c) E. oxypetalum.
(Agilent Technologies, Palo Alto, CA) and the compounds
detected were identified with the mass spectral database of
NIST, USA.
Endpoints for toxicity prediction by QSAR-TEST
The compounds identified through GC-MS analysis were eval-
uated for their toxicity using QSAR – Toxicity Estimation
Software Tool (TEST), Version 4.2 (Martin 2016). The end-
points for the analysis were Daphnia magna (LC50-48 h),
Pimephales promelas (LC50-96 h), Tetrahymena pyriformis
(IGC50-48 h), and Oral rat (LD50). The toxicity values predicted
for the compounds were correlated with aquatic toxicity and
mammalian toxicity scales (Category X: Extreme toxicity; A:
Very high toxicity; B: High toxicity; C: Moderate toxicity; and
D: Low toxicity) according to Agency for Toxic Substances
and Disease Registry (ATSDR). In addition, the bioaccumula-
tion factor (BF), developmental toxicity (DT), and mutagenic-
ity of the compounds were also studied. The prediction of
bioaccummulation factor through QSAR-TEST was based on
the data compiled from Dimitrov et al. (2005), Arnot and
Gobas (2006), EURAS bioconcentration factor (BCF) Gold
Standard Database, and Zhao et al. (2008). The developmen-
tal toxicity was predicted based on the data from Arena et al.
(2004), Sussman et al. (2003), Briggs et al. (2012), and
(Shepard and Lemire, 2004). Based on the response of

compounds to Ames test, the mutagenicity of the com-
pounds was predicted using the data set established by
Hansen et al. (2009). Different methods were employed to
evaluate the toxicity, such as Hierarchial clustering, single
model, group contribution, nearest neighbor, and consensus,
as applicable for each of the endpoint. Hierarchical clustering,
single model, group contribution, food and drug administra-
tion (FDA), and nearest neighbor models were employed to
predict the bioaccumulation factor and the toxicity against D.
magna and P. promelas. The toxicity was predicted against T.
pyriformis through hierarchical clustering, group contribution,
FDA, and nearest neighbor models. Hierarchical clustering,
FDA, and nearest neighbor models were used to predict the
mutagenicity and toxicity of the compounds against rat
(oral). The developmental toxicity of the compounds was pre-
dicted through hierarchical clustering, single model, FDA, and
nearest neighbor models. The consensus method was chosen
for the present study, as it takes into consideration of all the
above stated models for the prediction of toxicity.
Results
Analysis by GC-MS revealed the presence of 10 compounds
in C. angustifolium (C1–C10); 9 in C. carandas (C10–C18), and
10 in E. oxypetalum (C18–C27). The GC-MS chromatograms of
the three plants are presented in Figure 1. The isolated com-
pounds were labeled as C1 to C27 (Table 1).
Among the 27 compounds studied, four compounds, i.e.,
C21, C22, C23, and C27 detected in the extract of E. oxypeta-
lum were predicted to possess extreme toxicity (Category X)
based on their LC50 (mg/L) recorded against the plankton –
D. magna. Very high toxicity (Category A) was recorded for
the compounds C4, C5, C6, C9, C12, C17, and C18. The com-
pounds C2, C3, C7, C10, C11, C13–C16, C19, C20, C24, and
C26 were predicted to possess high toxicity (Category B).
Against T. pyriformis, the compounds C4, C6, C9, C12, and
C15 showed extreme toxicity. The compounds C5, C10, C11,
C14, C17, C18, C19, and C24 recorded very high toxicity while
C2, C3, C7, C13, and C20 were highly toxic. The toxicity was
categorized based on the IGC50 recorded against
T. pyriformis.
The compounds C6, C12, C15, C21, C22, and C23 were
predicted to possess extreme toxicity, with their LC50 values
less than 0.1 mg/L against P. promelas. The compounds C2,
C3, C5, C7, C9, C10, C14, C16, C18, and C24 showed very
high toxicity, whereas C1, C4, C8, C11, C13, C17, C19, C20,
and C26 were predicted to possess LC50 in the range
1–4.69 mg/L and hence, categorized in Category B (high tox-
icity) of the toxicity scale.
The compounds C1 &andC8 from C. angustifolium exhib-
ited moderate toxicity against the rat model, with the
respective LD50 values of 11.43 and 31.12 mg/kg. Low toxicity
was predicted in the compounds C3 (from C. angustifolium),
C22, C23, and C26 (from E. oxypetalum). All the compounds
detected in the extract of C. carandas possessed LD50 above
500 mg/kg, thus classified as nontoxic against rat, according
to the mammalian toxicity scale of ATSDR, EPA. The toxicity
DRUG AND CHEMICAL TOXICOLOGY 3
values predicted for the compounds against D. magna,
T. pyriformis, P. promelas, and rat are presented in Table 1.
High bioaccumulation factor was recorded from the com-
pounds of E. oxypetalum – C21, C23, and C22, with their val-
ues 981.97, 507, and 475.83, respectively. This was followed
by C17 (130.9) and C15 (109.77) from C. carandas. The BF val-
ues for all the other compounds were less than 100.
Among the compounds studied, 15 compounds were
developmental toxicants and 10 (C2, C4, C5, C6, C9, C10, C11,
C13, C18, and C24) were nontoxicants. Of the toxicants, four
compounds were from C. angustifolium (C1, C3, C7, and C8)
and four from C. carandas (C12, C14, C16, and C17). Among
the compounds detected from E. oxypetalum, C18 and C24
were developmental nontoxicants, while C19–C23, C25, and
C26 were toxicants. Dasycarpidan-1-methanol, acetate (ester)
was the only compound that was predicted to be a mutagen,
while all other compounds were non-mutagens. The bio-
accumulation factor, developmental toxicity and mutagenec-
ity of the compounds studied are represented in Table 2.
Discussion
The current study predicts the toxicity of natural compounds
detected in the methanolic extract of C. angustifolium, C. car-
andas, and E. oxypetalum, against different end points using
QSAR-TEST.
The pharmacological activities of these plants have been
documented (Dhar et al. 1974, Hegde et al. 2009, Upendra
and Khandelwal 2012, Dandekar et al. 2015, Kaunda and
Zhang 2017). However, studies on their toxicity are scarce.
Hence, evaluation of their toxicity may provide information
on further use of the natural compounds in differ-
ent industries.
To relate the physiochemical properties to biological activ-
ity, relevant descriptors called molecular descriptors (MD) are
used. The relevance of molecular descriptors in toxicity pre-
diction depends on the endpoints, concerned biological sys-
tem and class of chemicals (Balls et al. 2012). More than 2000
molecular descriptors such as molecular volume, shape,
dipole moment, the number of atoms, steric effect, refractiv-
ity, dissociation constant, electronegativity, octanol/water par-
tition coefficient can be generated and used for in silico
predictions (Hansch 1993, Todeschini and Consonni 2008).
One such tool in evaluating the toxicity of any compound is
Toxicity Evaluation Software Tool (TEST), which integrates
and predicts the toxicity based on the compound’s toxic
mechanism and critical structural similarities. Thus, the multi-
species toxicity of natural compounds was evaluated using
QSAR-TEST in this study.
With the advent of QSAR prediction systems, the accuracy
of toxicity evaluation of natural compounds can be improved
significantly. The applicability domain in a QSAR model
defines the physicochemical, structural, or biological informa-
tion of compounds (Balls et al. 2012). The applicability
domain of hierarchical clustering, single model, and group
contribution models is based on the model ellipsoid, Rmax,
and fragment constraints. In addition to model ellipsoid and
fragment constraints, the cosine similarity coefficient and
 4

Table 1. Predicted toxicity values and category of natural compounds against D. magna, T. pyriformis, P. promelas, and rat.
D. magna T. pyriformis P. promelas Rat
LC50 IGC50 LC50 LD50
Compound ID Plant Name of the compound (mg/L) Category (mg/L) Category (mg/L) Category (mg/kg) Category
C1 C. angustifolium Carda-4,20(22)-dienolide, 3-[(6-deoxy-3-O- N/A N/A N/A N/A 3.64 B 11.43 C
SRIPRIYA N. ET AL.

methyl-a-L-mannopyranosyl)oxy]-14-hydroxy-
, (3a)-
C2 Chloromethyl 2-chloroundecanoate 2.61 B 1.20 B 0.75 A 1602.62 NT
C3 Dasycarpidan-1-methanol, acetate (ester) 1.32 B 3.24 B 0.23 A 286.89 D
C4 Octadecanoic acid, 9,10-dichloro-, methyl ester 0.47 A 0.07 X 1.77 B 830.49 NT
C5 9-Octadecenoic acid (Z)-, methyl ester 0.74 A 0.28 A 0.57 A 15,279.68 NT
C6 Oleic acid, eicosyl ester 0.79 A 0.0011 X 0.0352 X 28,662.33 NT
C7 4-Piperidineacetic acid, 1-acetyl-5-ethyl-2-[3-(2- 5.93 B 5.37 B 0.14 A N/A N/A
hydroxyethyl)-1H-indol-2-yl]-a-methyl-,
methyl ester
C8 Sarreroside N/A N/A N/A N/A 1.47 B 31.12 C
C9 Docosanedioic acid, dimethyl ester 0.95 A 0.0996 X 0.14 A 20,476.93 NT
C10 C. angustifolium; Hexadecanoic acid, methyl ester 1.78 B 0.56 A 0.36 A 15,356.82 NT
C. carandas
C11 C. carandas 9-Octadecenoic acid (Z)-, 2-hydroxy-1- 1.14 B 0.80 A 4.69 B 13,511.72 NT
(hydroxymethyl)ethyl ester
C12 Hexadecanoic acid, 1-(hydroxymethyl)-1,2- 0.24 A 0.0112 X 0.0083 X 21,073.39 NT
ethanediyl ester
C13 n-Hexadecanoic acid 4.58 B 1.28 B 1.31 B 13,454.34 NT
C14 Oleic acid 1.16 B 0.37 A 0.14 A 12,911.86 NT
C15 17-Pentatriacontene 5.28 B 0.0018 X 0.0011 X 7505.29 NT
C16 Pregnan-18-oic acid, 20-hydroxy-, (5a)- 7.84 B N/A N/A 0.40 A 8231.46 NT
C17 3,7,11,15-Tetramethyl-2-hexadecen-1-ol 0.37 A 0.12 A 1 B 7554.77 NT
C18 C. carandas; 10-Octadecenoic acid, methyl ester 0.72 A 0.28 A 0.57 A 15,263.11 NT
E. oxypetalum
C19 E. oxypetalum 1,2-Benzenedicarboxylic acid, butyl octyl ester 3.98 B 0.52 A 1.21 B 15,853.27 NT
C20 1,2-Benzenedicarboxylic acid, mono(2- 2.68 B 5.24 B 3.53 B 6782.54 NT
ethylhexyl) ester
C21 Cyclopropanebutanoic acid,2-[(2-[(2-[(2- 0.03 X N/A N/A 0.0062 X 2002.69 NT
pentylcyclopropyl)methyl]
cyclopropyl)methyl]cyclopropyl)methyl]-,
methyl ester
C22 17-(1,5-Dimethylhexyl)-10,13-dimethyl-3- 0.0153 X N/A N/A 0.0019 X 427.05 D
styrylhexadecahydrocyclopenta(a)
phenanthren-2-one
C23 Ergosteryl acetate 0.0229 X N/A N/A 0.0249 X 112.26 D
C24 Ethanol, 2-(9-octadecenyloxy)-, (Z)- 1.13 B 0.19 A 0.97 A 10,547.27 NT
C25 Glycine, N-[(3a,5a,7a,12a)-24-oxo-3,7,12- N/A N/A N/A N/A N/A N/A 559.75 NT
tris[(trimethylsilyl)oxy]cholan-24-yl]-,
methyl ester
C26 (5a)Pregnane-3,20a-diol, 14a,18a-[4-methyl-3- 6.35 B N/A N/A 3.35 B 485.26 D
oxo-(1-oxa-4-azabutane-1,4-diyl)]-, diacetate
C27 Rhodopin 0.0000881 X N/A N/A N/A N/A N/A N/A
X: Extreme toxicity; A: very high toxicity; B: high toxicity; C: moderate toxicity; D: low toxicity; NT: nontoxic; N/A: not applicable.
Table 2. Predicted values of bioaccumulation factor, developmental toxicity, and mutagenicity of natural compounds.
Developmental toxicity Mutagenicity
Bioaccumulation
Compound ID Plant Name of the compound factor Value Result Value Result
C1 C. angustifolium Carda-4,20(22)-dienolide, 3-[(6-deoxy-3-O-methyl-a-L- N/A 0.60 T 0.03

mannopyranosyl)oxy]-14-hydroxy-, (3a)-
C2 Chloromethyl 2-chloroundecanoate 44.61 0.42 NT 0.28

C3 Dasycarpidan-1-methanol, acetate (ester) 57.87 0.85 T 0.69 þ
C4 Octadecanoic acid, 9,10-dichloro-, methyl ester 45.54 0.44 NT 0.33

C5 9-Octadecenoic acid (Z)-, methyl ester 77.58 0.47 NT 0.11

C6 Oleic acid, eicosyl ester 33.44 0.43 NT 0.14

C7 4-Piperidineacetic acid, 1-acetyl-5-ethyl-2-[3-(2- 11.78 0.80 T 0.13

hydroxyethyl)-1H-indol-2-yl]-a-methyl-,
methyl ester
C8 Sarreroside N/A 0.70 T 0.10

C9 Docosanedioic acid, dimethyl ester 24.74 0.44 NT 0.17

C10 C. angustifolium; Hexadecanoic acid, methyl ester 44.45 0.44 NT 0.02

C. carandas
C11 C. carandas 9-Octadecenoic acid (Z)-, 2-hydroxy-1- 12.21 0.49 NT 0.29

(hydroxymethyl)ethyl ester
C12 Hexadecanoic acid, 1-(hydroxymethyl)-1,2- 9.11 0.61 T 0.18

ethanediyl ester
C13 n-Hexadecanoic acid 29.05 0.27 NT
0.04

C14 Oleic acid 16.55 0.51 T 0.01

C15 17-Pentatriacontene 109.77 N/A N/A
0.01

C16 Pregnan-18-oic acid, 20-hydroxy-, (5a)- 27.32 1.02 T 0.25

C17 3,7,11,15-Tetramethyl-2-hexadecen-1-ol 130.90 0.61 T
0.05

C18 C. carandas; 10-Octadecenoic acid, methyl ester 77.55 0.43 NT 0.11

E. oxypetalum
C19 E. oxypetalum 1,2-Benzenedicarboxylic acid, butyl octyl ester 17.82 0.54 T
0.03

C20 1,2-Benzenedicarboxylic acid, mono(2- 9.40 0.78 T
0.02

ethylhexyl) ester
C21 Cyclopropanebutanoic acid,2-[(2-[(2-[(2- 981.97 0.64 T 0.40

pentylcyclopropyl)methyl]cyclopropyl)methyl]
cyclopropyl)methyl]-, methyl ester
C22 17-(1,5-Dimethylhexyl)-10,13-dimethyl-3- 475.83 0.94 T 0.18

styrylhexadecahydrocyclopenta(a)phenanthren-
2-one
C23 Ergosteryl acetate 507 0.90 T 0.09

C24 Ethanol, 2-(9-octadecenyloxy)-, (Z)- 42.20 0.40 NT 0.12

C25 Glycine, N-[(3a,5a,7a,12a)-24-oxo-3,7,12- 13.73 0.52 T 0.09

tris[(trimethylsilyl)oxy]cholan-24-yl]-, methyl ester
C26 (5a)Pregnane-3,20a-diol, 14a,18a-[4-methyl-3-oxo-(1- 10.53 0.77 T 0.29

oxa-4-azabutane-1,4-diyl)]-, diacetate
C27 Rhodopin N/A N/A N/A 0.05

T: toxicant; NT: nontoxicant; N/A: not applicable;
: negative; þ: positive.
DRUG AND CHEMICAL TOXICOLOGY
5
6 SRIPRIYA N. ET AL.
cross validation coefficient are considered for the FDA model.
In the nearest neighbor model, the major applicability
domain is the cosine similarity coefficient. The consensus
model includes the applicability domains that are valid for
the respective models. Only the activity of molecules falling
within the applicability domain of the model can be pre-
dicted. In the present study, toxicity prediction by consensus
model is presented, since the model takes an average esti-
mates from multiple models and compensates the limitations
of the individual models. Individual models use different
descriptors and statistical methods to model different aspects
of the toxicological effects. The toxicity could not be pre-
dicted through consensus model for few of the compounds
in the present study, due to the non-applicability of two or
more QSAR models. The predicted toxicity values for each of
the endpoints, molecular descriptors and number of similar
chemicals studied through different models are provided in
the supplementary material (Tables S1–S7). From the results
of the present study, it could be noted that the plant com-
pounds had high toxicity for lower organisms which grad-
ually decreased with higher order of organisms in the order,
D. magna > T. pyriformis > P. promelas > Rat (Oral).
Bioaccumulation factor is the ratio of the concentration of
a chemical in fish due to absorption via the respiratory sur-
face with respect to water at steady state. In general, a com-
pound is termed bioaccummulative, if its BF value is greater
than 2000 and very bioaccummulative if its value is greater
than 5000 (Burden et al. 2014). In the present study, the bio-
accumulation factor for all the compounds was less than
2000, and hence, non-bioaccummulative in nature.
Developmental toxicity defines whether a particular chemical
causes any effect that hinders normal development, both
before and after birth. Most of the compounds i.e., 15 out of
27 studied from the plants – C. angustifolium, C. carandas,
and E. oxypetalum were developmental toxicants.
Compounds that are positive to Ames mutagenicity test are
regarded as potential carcinogens (Griffiths et al. 2000). The
non-mutagenicity of the 27 compounds studied, except for
Dasycarpidan-1-methanol, acetate (ester), suggests that the
compounds can be explored in different industries.
Among the different endpoints studied for the com-
pounds, experimental data were available for toxicity against
rat and mutagenicity for few compounds. The LD50 values of
25,006.29 and 1341.65 mg/kg were recorded for Oleic acid
and 1,2-Benzenedicarboxylic acid, mono(2-ethylhexyl) ester
respectively, in ChemidPlus database. The predicted toxicity
values assessed for these compounds and the experimental
values are observed to fall under the same toxicity scale, i.e.,
nontoxic category. Similarly, experimental values were
recorded in the toxicity benchmark database, for the com-
pounds – 9-Octadecenoic acid (Z)-, methyl ester; n-hexadeca-
noic acid; oleic acid and 10-Octadecenoic acid, methyl ester.
The predicted values correlated with the experimental results,
thus confirming the non-mutagenicity of these compounds.
Most of the marketed phytomedicines constitute extracts
of whole plant or a plant part and their therapeutic efficacy
is considered to be from the interactions of the plant constit-
uents. These interactions arise from the synergy, enhanced
bioavailability or antagonism exhibited by one or more
constituents (Nelson and Kursar 1999, Williamson 2001).
However, the exact mechanism of drug action largely relies
on experimental and clinical evidence. In silico studies pro-
vide insights on the interactions of the constituents of phyto-
medicines and their toxicity. The toxicity of natural
compounds from plants has previously been documented by
the same authors (Prakash et al. 2014, Udayaprakash et al.
2014). Evaluation of toxicity through in silico models over-
comes the consumption of time, money, and workforce
involved in screening of drug targets during preclinical stud-
ies. Additionally, the use of animals for toxicity estimation
can be limited through in silico studies. In the present study,
the toxicity of individual compounds present in the plants –
C. angustifolium, C. carandas, and E. oxypetalum was eval-
uated through QSAR-TEST. Further studies on the interactions
between the compounds of the respective plants through in
silico tools such as docking are recommended prior to in
vivo studies.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This research was supported by internal fund of R & D, Marina Labs,
Chennai [Grant no. ML-2015-RD002].
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