STUDI HUBUNGAN KUANTITATIF STRUKTUR-AKTIFITAS (HKSA)SENYAWA TURUNAN 4-AMINOQUINOLIN PIRIMIDIN, DOCKING MOLEKUL, PENELUSURAN FARMAKOFOR, VIRTUAL SCREENING, UJI TOKSISITAS, DAN PROFIL FARMAKOKINETIK SEBAGAI ANTIMALARIA SECARA IN SILICO
Abstrak: A research of
quantitative structure-activity relationship (QSAR), molecular docking,
searching pharmacophore, virtual screening, toxicity test, and Pharmacokinetic
Profile of 4-Aminoquinoline Pyrimidine Derivative Compounds as Plasmepsin
enzyme inhibitor as Antimalarial by in silico has been conducted. This study
aims to find the QSAR model equation of 4-Aminoquinoline Pyrimidine derivative
compounds, to find pharmacophore
features of compounds that responsible for inhibition activity of Plasmepsin
enzyme in Plasmodium falciparum, as well as to select compounds from virtual
screening results then determine the pharmacocinetic profile, and the toxicity
of metabolites for malaria treatment. The procedure begins with the modelling
and ab initio geometry optimization of the molecular structure by HyperChem
8.0. QSAR descriptors calculation, pharmacophore feature determination and
molecular docking are done by using MOE 2009. Furthermore, toxicity testing by
Toxtree and AdmetSAR, as well as pharmacokinetic profile determination by using
PreADME done to 150.000 natural product compounds from zinc database. From the
experiments, the equation obtained: 1/IC50 = 5.3757 + (0.7514 AM1_HOMO) +
(-0.3100 log P (o/w)) + (0.0065 vdw_vol), where r2 = 0.9282 dan q2 = 0.9282, beside
that molecular docking results for protein code 2IGX compound 13 showed better
results with the value of docking score (S) is -129.7491. As for the compounds of zinc database, the
result is a compound with code ZINC32501354 and ZINC32501366 are choosen
compound among 150.000 compounds in terms of suitability of the pharmacophore
query, docking by pharmacophore method, bioavailability prediction using
Lipinski rule of five and from the prediction of ADME/T
KATA KUNCI: QSAR; molecular
docking; pharmacophore; antimalarial; Plasmepsin enzyme
Penulis: Nursalam Hamzah,
Afrisusnawati Rauf, Ariwanti
Kode Jurnal: jpfarmasidd150666
