Figure C 4: GC-MS Chromatogram for 1,2-Benzenedicarboxylic acid, butyl
2-methylpropyl ester (1,2BAB-2-MPE)
Figure C 3 and Supplementary Table S9, presents, GC-MS fragmentation
analysis of Geraniin (98% w/w), revealed 20 compounds with
1,2-Benzenedicarboxylic acid, butyl 2-methylpropyl ester (1,2BAB-2-MPE)
(18.509%), Phytol, acetate (16.05%) and
3,7,11,15-Tetramethyl-2-hexadecen-1-ol (12.46%) as the compounds with
the highest compositions. The compound
3,7,11,15-Tetramethyl-2-hexadecen-1-ol have also been identified in
methanolic leaf extracts of the Annona muricata and reported to
possess cancer-preventive, antimicrobial, anti-inflammatory
anti-diuretic and anti-oxidant properties
(Shibula and Velavan, 2015). The
antiviral compound, 1,2-Benzenedicarboxylic acid, butyl 2-methylpropyl
ester (1,2BAB-2-MPE) as presented in Figure C 4 below, is reported for
the first time as a fragment of Geraniin.
Phytol, acyclic diterpene alcohol was identified as one of the compounds
in Geraniin fragments ethanolic crude (SME), SMEH, SMEDCM, SMMH and
SMMDCM . Phytol was previously reported by other researchers to exhibit
anti-cancer, anti-microbial and anti-oxidant activities
(Cos et al., 2006,
Costa et al., 2012a,
Costa et al., 2012b,
Silva et al., 2014) and could be
responsible for synergistic pharmacological action of these extracts.
Phytol has been reported to be identified in hydroethanolic extracts ofAbutilon indicum used in the Indian system of medicine
(Thakor et al., 2016). Therefore the
identification of phytol in the ethanolic extracts is in line with our
findings.
Table S 10, presents a similarity table of compounds identified in GC-MS
analysis of Geraniin and fractionated alcoholic leaf extracts ofS. mombin . In the comparative GC-MS analysis of SM leaf extracts
and Geraniin fragments, as presented in Table S 10, similar
compounds such as 1-Tetradecene and n-Nonadecanol-1 found in Geraniin
were also identified in all fractionated alcoholic leaf extracts. As
previously established in the background literature, Geraniin, found inS mombin and other extracts from the plant is known to have
several pharmacological activities. This underscores the pharmacological
potential of the plant and its compounds. Fragmentation of large
molecules to smaller and simpler compounds could increase the
drug-likeness, bioactivity, increased bioavailability and decreased
toxicity(FA. Olotu et al., 2018). In our previous in
silico study, Geraniin was identified as a potential anti-Ebola
candidate. A pharmacophore model generated from Geraniin, showed that
there were three aromatic rings, a hydrophobic ring and several hydrogen
donors/acceptors responsible for anti-Ebola activities
(Boadu et al., 2021). This model could be
a volatile or contaminant of Geraniin. Hence, Geraniin was subjected to
GC-MS analysis to identify possible volatile(s) that could be close to
the pharmacophore model and to also create uniformity in methodology
used in the identification of antiviral phytochemicals in the alcoholic
leaf extracts and also to identify the active volatile compound(s)
(Chauhan et al., 2014). Twenty (20)
fragments of compounds were identified from the chromatogram of Geraniin
as indicated in Table S9. Out of the 20 compounds,
1,2-Benzenedicarboxylic acid, butyl 2-methyl propyl ester was the only
compound that has been reported in the literature to possess anti-viral
and antimicrobial activities (FUNGI,
Govindappa et al., 2014). Hence its use
in molecular docking in this present study.
Table 2, summarises selected phytochemical compounds from GC-MS
analysis of crude and fractionated extracts and Geraniin (98 %w/w) with
reported anti-viral properties. It also shows the computed
physicochemical descriptors as well as predict Absorption, Distribution,
Metabolism, and Excretion (ADME), of the identified anti-viral
phytochemicals.
The physicochemical and pharmacokinetic properties in the early days of
the inception of drug discovery were normally predicted and the last
stage of the drug design process, but it is important to predict ADME
properties of the potential drug candidate, to decrease the cost of drug
discovery research as ADME, normally contributes to failures of drug
molecules of more than 50% (Mandlik et
al., 2016).
This study identified a monoterpene, p-Cymene, in the SMM crude and SMEH
fractions of S. mombin leaf extracts. p-Cymene in literature has
been reported to possess anti-viral, anti-oxidant, anti-inflammatory,
anti-parasitic, anti-diabetic, anti-fungal, and anti-cancer effects in
both in vivo and in vitro studies of the molecule
(Panikar et al., 2021,
Balahbib et al., 2021,
Sharifi-Rad et al., 2018) In addition, a
derivative of p-Cymene known as Thymol with a percentage composition of
0.5% and 0.21% was found in SMM and SMEDCM respectively with reported
antimicrobial, anti-inflammatory, anti-oxidant activity
(Braga et al., 2006) and anti-viral
properties against spike glycoprotein of SARS-CoV-2
(Kulkarni et al., 2020). Furthermore,
D-Limonene, another monoterpene, was detected in SMMDCM with a
percentage composition of 0.34 %, has been reported to possess
anti-SARS-CoV-2 activity in silico(Panikar et al., 2021) and antimicrobial
properties in vitro (Zahi et al., 2015).
Reported by other authors, L-alpha-Terpineol, a monoterpenoid, is known
to exhibit various pharmacological activities such as anti-Covid-19
activity in silico (Gul et al.,
2020), anticonvulsant, sedative, antinociceptive, and hypotensive
effects (Aronsson et al., 2017,
Khaleel et al., 2018). We identified
L-alpha-Terpineol in both SMMH and SMEH with percentage composition of
0.44% and 1.40%, respectively. The phytochemical L-alpha-Terpineol has
been reported to have anti-CoVID-19 properties in silico by
(Panikar et al., 2021), while its
anti-oxidant and disinfectant properties were identified by
(Cours, 2020).
In terms of Geraniin (98% w/w), we have reported in our previousin silico study to possess anti-Ebola and anti-SARS-CoV-2
properties against EBOV secreted Glycoprotein (sGP) and a possible
inhibitor interferes with the functioning of SARS-CoV-2 targets
(Boadu et al., 2022,
Boadu et al., 2021). During the
anti-Ebola study, a pharmacophore model generated showed that three
aromatic rings, a hydrophobic ring and several hydrogen donors/acceptors
were responsible for ant-Ebola activities, although it violated
Lipinski’s rule of five (Lipinski,
Lipinski et al., 1997).
Table 2 : Summary of
identified anti-viral phytochemical compounds from GC-MS analysis of SM
crude and fractionated leaf extracts with their reported pharmacological
action and computed physicochemical descriptors as well as predict
Absorption, Distribution, Metabolism, and Excretion (ADME), of the
identified anti-viral phytochemicals.