LIGNAN DERIVATIVES POTENTIAL AS PLASMODIUM FALCIPARUM LACTATE DEHYDROGENASE INHIBITORS: MOLECULAR DOCKING APPROACH OF ANTIPLASMODIAL DRUG DESIGN
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2015, Vol 7, Issue 11
Abstract
Objectives: To investigate the lignan derivatives potential as Plasmodium falciparum Lactate Dehydrogenase (PfLDH) inhibitors by using Computer Aided Drug Design (CADD) and molecular docking approach.Methods: In finding potential antiplasmodial, in silico approach has been utilized. Protein structure of PfLDH has been built through homology modeling. Kobamin has been used to refine the 3D PfLDH structure. Structure validation of PfLDH was done by Ramachandran Plot and ERRAT calculations. The validated PfLDH was ready for molecular docking analysis. lignan derivatives as lead compounds were designed. The pharmacophore of lignan derivatives were assessed by using Molsoft drug likeness. Both protein and Lignan derivatives were docked with Autodock Vina. The best docking score was shown by the lowest affinity energy.Results: Homology modeling of PfLDH has been built. Moreover, PfLDH refinement and validation were importantly conducted to ensure that PfLDH structure was in good quality. According to Ramachandran Plot and Procheck analysis, PfLDH has good structure quality with 93.39% confidence value. On the other hand, lignan derivatives assessment also has been done by evaluating their physicochemical and pharmacophore properties as lead compounds. From this assessment, it showed that Aristoligol (ARG1), Aristoligone (ARG2), and Ester Asetil Aristoligol (ARG3) showed good compounds to be drug likeness by following Lipinski’s rule of five (RO5), while Ester Butiril Aristoligol (ARG4) showed poor RO5 criteria. Bioavailability of four compounds was good in body metabolism, however, ARG3 and ARG4 could not be lead like compounds due to poor lead likeness value. From molecular docking result, the most favorable binding with PfLDH was ARG4 based on its affinity energy value (-8.0 kj/mol), followed by ARG3, ARG2 and ARG1, respectively.Conclusions: The identification of potential anti plasmodial drugs was successfully accomplished by evaluating synthetic lignan derivatives compound through physicochemical properties and molecular docking analysis. Overall, physicochemical and pharmacophore properties showed good result. Molecular docking interaction has distinct mode interactions of lignan derivatives with PfLDH. We believe that these evaluated compounds could be used as anti plasmodial drugs according to in silico evaluation results.Â
Authors and Affiliations
Rosmalena . , Vivitri Dewi Prasasty, Muhammad Hanafi, Emil Budianto, Berna Elya
Keywords
Related Articles
- EP ID EP578343
- DOI -
- Views 58
- Downloads 0
PHARMACOEPIDEMIOLOGICAL SURVEY ON THE USE OF COSTUS PICTUS (INSULIN PLANT) IN CENTRAL KERALA
Objective: Costus pictus commonly known as spiral ginger or insulin plant is grown in gardens as ornamental plant especially in Kerala and used to control sugar levels. The objective of the present survey was to collect...
ANTI-TUMOUR ACTIVITY OF BROMOPYRROLE ALKALOIDS AGAINST HUMAN BREAST TUMOUR (MCF-7) THROUGH APOPTOSIS INDUCTION
Objective: The present study was conducted to screen the cytotoxicity and initiation of apoptosis in MCF-7 human breast tumour cells using the Indian sponge Acanthostylotela cornuta of the Gulf of Mannar. Methods: The c...
NOVEL ISOCRATIC REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CIPROFLOXACIN AND PHENAZOPYRIDINE IN SOLID DOSAGE FORM
Objective: To develop a new, simple, validated reverse phase high performance liquid chromatography (RP-HPLC) method for the simultaneous quantitative determination of Ciprofloxacin (CFX) and Phenazopyridine (PZD) in com...
SERUM ANTI-ZONA PELLUCIDA ANTIBODIES IS CORRELATED WITH ESTRADIOL LEVEL IN WOMEN WITH IN VITRO FERTILIZATION FAILURE
Objective: In vitro fertilization (IVF) is one of the several assisted reproductive technologies (ART) used to aid infertile couples to conceive a child. Many factors affecting the rate of success of IVF cycle. The aim o...
PREPARATION AND EVALUATION OF METRONIDAZOLE SUSTAINED RELEASE FLOATING TABLETS
Objective: The objective of the present study is the preparation of metronidazole (MZ) floating tablets that are designed to retain in the stomach for a long time for better eradication of Helicobacter Pylori (H. pylori)...