EDI PRIYO UTOMO (2012) Eksplorasi Alkaloid Dari Erythrina crista-galli Sebagai Antimalaria Melalui Inhibisi Enzim Dihidrofolat Reduktase Berdasarkan Kajian In silico dan In vitro. Disertasi thesis, UNIVERSITAS AIRLANGGA.

Preview	Text (ABSTRAK) gdlhub-gdl-s3-2012-utomoedipr-20944-6.abstr-k.pdf Download (304kB) | Preview
	Text (FULL TEXT) gdlhub-gdl-s3-2012-utomoedipr-20944-Fk.pdf Restricted to Registered users only Download (10MB) | Request a copy

Abstract

Exploration on the alkaloid compounds in plant extracts of dadap merah (Erythrina crista-galli) was carried out to search for secondary metabolites which has antimalarial activity. One of the survival ability of the malaria parasite life cycle is to use dihydrofolate reductase (DHFR) which converts dihydrofolate acid into tetrahydrofolate acid, a precursor for the synthesis of purine and thymidine bases. Therefore, an alkaloid that has successfully identified as inhibitor for its ability on inhibition on enzyme activity.Flowers and roots of dadap merah taken as samples in this study. Both samples were separated into its alkaloids by means of extraction followed by separation using column chromatography and thin layer chromatography. Elucidation on the structure of the alkaloids were performed by using UV-VIS, FTIR and NMR spectroscopy, and supported by LC-MS/MS to determine its molecular mass. Ability of the alkaloid isolates to inhibit the enzymes activity (IC50, μg/ml) was carried out on the recombinant human enzyme (hDHFR) and crude extract of P. berghei (PbDHFR). The efficacy of the isolate containing alkaloid compound act as inhibitors against to the both enzyme of hDHFR and PbDHFR are 8-oxo-erythraline> erythrinine> erythraline. In the in silico approach shows the inhibitory activity of the hDHFR enzyme would be affected by its dipole moment. Increasing in polarity of the alkaloid, the inhibition constant (Ki) will be increased. The active site of both enzyme contain an amino acid residue which has a hydrophilic group, such as serine (Ser) which perform a hydrogen bonding with methylene dioxy or hydroxyl group and the hydrophobic interaction was performed by residue of phenylalanine (Phe). The efficacy of the erythrina alkaloid will disappear when a mutation of the residue of active site taken place. The hydrophobic group of amino acid residue such as phenylalanine face to benzenoid ring of alkaloid in van der Waals interaction. Conclusion proposed that the interaction between the ligand with the receptor of the enzyme affected by the presence hydrophilic group of of functional groups in alkaloids.

Actions (login required)

View Item