Identification of potential targets for Thymidylate Synthase and Amp-C βlactamase from of non-alkaloidal fractions of Moringa oleifera leaves.

AIM The aim of present investigation is to identify the potential targets for Thymidylate Synthase and Amp-C βlactamase from of non-alkaloidal fractions of Moringa oleifera leaves. BACKGROUND Bioactive constituents from medicinal plants, either as pure compounds or as crude form, 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 the nonalkaloidal fractions of ethanolic leaf extract of Moringa oleifera. Then, the identified phytoconstituents were used to ensure the potential target molecules for the binding affinity towards the target proteins viz. Thymidylate Synthase (1HVY) and Amp-C beta-lactamase (1FSY) by docking analysis. METHODS In the present investigation, ethanolic extract of Moringa leaves was prepared and then fractionated on the presence/absence of alkaloids. The antimicrobial activity of different fractions of ethanolic leaf extract was evaluated against various pathogens. 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 the 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. Also, 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.