Identification of Potential Targets for Thymidylate Synthase and Amp-C β-lactamase from Non-alkaloidal Fractions of Moringa oleifera Leaves
Authors: Kumari Chandresh , Virk Amanpreet K. , Kumari Swati , Gupta Tanvi , Rolta Rajan , Li Xiangkai , Kulshrestha Saurabh 
Published: January 2021

Aim:
The aim of present investigation is to identify the potential targets for Thymidylate
Synthase and Amp-C β-lactamase from non-alkaloidal fractions of Moringa oleifera leaves.

Background:
Bioactive constituents from medicinal plants, either as pure compounds or as crude
forms, provide vast opportunities for new drug discoveries. Due to an increasing demand for chemical
diversity in screening programs, seeking therapeutic drugs from natural products, mainly from edible
plants, has grown throughout the world. Moringa oleifera has an impressive range of medicinal uses
with high nutritional value. Therefore, this medicinal plant has been used widely in traditional Indian
medicine for anti-inflammation, anticancer and antibacterial infections.

Objectives:
The primary objective is to identify the phytoconstituents present in the maximum proportion
in non-alkaloidal fractions of ethanolic leaf extract of Moringa oleifera. Then, the identified phytoconstituents
were used to ensure the potential target molecules for binding affinity towards the target
proteins viz. Thymidylate Synthase (1HVY) and Amp-C beta-lactamase (1FSY) by docking analysis.

Methods:
In present investigation, ethanolic extract of Moringa leaves was prepared and then fractionated
on the basis of presence/absence of alkaloids. The antimicrobial activity of different fractions
of ethanolic leaf extract was evaluated against various pathogens. Later, after this, bioactive molecules
present in the non-alkaloidal fractions of ethanolic leaf extract were accomplished through GC-MS analysis,
and finally, the identified phytocompounds were analyzed through docking studies to evaluate their
affinity for target proteins viz. Thymidylate Synthase (1HVY) and Amp-C β-lactamase (1FSY).

Results:
The antimicrobial activity of non-alkaloidal fractions of ethanolic leaf extract was evaluated
against various pathogens which exhibited significant antimicrobial activity. Twenty phytocompounds
were identified as gas chromatogram of non-alkaloidal fractions (chloroform and ethyl acetate) of
leaf extract of M. oleifera; Four most prominent compounds having highest peak area percentage were
identified as Ethane, 1,1,2,2-tetrachloro, (46.45%) 2-Propanone, 1,1,3-trichloro, (13.77%) Heptasiloxane,
1,1,3,3,5,5,7,7,9,9,11,11,13,13-tetradecamethyl (17.87%) and 2,4-Dichlorodiphenylsulfone
(17.64%). Other notable compounds were 9,12-Octadecadienoic acid (Z,Z) (14.06%), Oleic acid, 3-
(octadecyloxy)propyl ester (12.41%), Fluoranthene (6.98%), Phenol, 2,4-bis( 1,1-dimethylethyl)
(4.16%) and Phthalic acid, butyl nonyl ester (3.47%). Only, five compounds viz. 2,6-Bis(1,1-
dimethylethyl)phenol(C1), Dodecamethylcyclohexasiloxane(C2), Chlorodimethylethylsilane(C3),
Fluoranthene(C4) and Hexadecanoic acid, methyl ester(C5) showed the maximum interaction with
1HVY with highest docking score of -178.51Kcal/mol, - 231.65Kcal/mol, -129.18Kcal/mol, -
173.10Kcal/mol and -220.78Kcal/mol, respectively. In addition, three compounds viz. Dodecamethylcyclohexasiloxane(
C2), Fluoranthene(C4) and Hexadecanoic acid, methyl ester(C5) showed the
maximum interaction with 1FSY with highest docking score of -137.23Kcal/mol, -54.34Kcal/mol and
-153.84Kcal/mol, respectively.

Conclusion:
Moringa plant may provide incredible capabilities to develop pharmacological products.
The present finding demonstrated that Moringa oleifera is an excellent plant candidate to be used for
improving the health of communities.