Open AccessIN SILICO STUDIES OF (S)-2-AMINO-4-(3,5-DICHLOROPHENYL) BUTANOIC ACID AGAINST LAT1 AS A RADIOTHERANOSTIC AGENT OF CANCER
Author(s) -
Holis Abdul Holik,
Faisal Ibrahim,
ABIB LATIFU FATAH,
Arifudin Achmad,
Achmad Hussein Sundawa Kartamihardja
Publication year - 2021
Publication title -
international journal of applied pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.238
H-Index - 15
ISSN - 0975-7058
DOI - 10.22159/ijap.2021.v13s4.43868
Subject(s) - autodock , chemistry , bifunctional , in silico , adme , docking (animal) , combinatorial chemistry , stereochemistry , molecular model , molecule , computational biology , biochemistry , organic chemistry , medicine , nursing , biology , in vitro , gene , catalysis
Objective: This study aims to obtain a good activity of radiotheranostic kit for cancer which is built by combining (S)-2-amino-4-(3,5-dichlorophenyl) butanoic acid (ADPB) with various bifunctional chelators.
Methods: This study was conducted through in silico method that consists of molecular docking simulation using AutoDock 4 as well as ADMET prediction using vNN-ADMET and Pre-ADMET. Six bifunctional chelators (i.e. CTPA, DOTA, H2CB-TE2A, H2CB-DO2A, NOTA, and TETA) were conjugated with ADPB as a carrier molecule and further analyzed through molecular docking and ADMET prediction.
Results: The results showed that the ADPB-NOTA has the best affinity with the Gibbs free energy (ΔG) of-7.68 kcal/mol with an inhibition constant of 2.36 µM and its ability to bind with the gating residue of LAT1 (ASN258) through hydrogen interactions. Besides that, the ADPB-NOTA compound has a good ADME profile and is predicted to be safe for human use.
Conclusion: This study showed that ADPB-NOTA is the most prospective candidate to be used as a radiotheranostic agent.