Host-Guest Interactions Between Betacyclodextrin And Selected Fluoroquinolones: A Molecular Modelling Study

• Main Author: Mousa Al-Wahsh, Saleh Ahmad
• Format: Thesis
• Language: English
• Published: 2016
• Subjects: RM300-666 Drugs and their actions
• Online Access: http://eprints.usm.my/31411/1/SALEH_AHMAD_MOUSA_AL-WAHSH_24.pdf; http://eprints.usm.my/31411/
• Institution: Universiti Sains Malaysia

Fluorokuinolon (FQs) ialah satu kumpulan antibiotik penting yang terdiri daripada gelang kuinolon hidrofobik dan gelang piperazina hidrofilik. Betasiklodekstrin (β-CD) dan terbitannya kini digunakan secara meluas dalam sistem penghantaran ubat, kerana rongga hidrofobiknya mampu membentuk kompleks rangkuman dengan pelbagai molekul organik. Dalam kajian ini, interaksi perumah tetamu antara FQs dan β-CD menggunakan tiga teknik permodelan molekul iaitu mekanik kuantum, pengedokan molekul dan dinamik molekul telah dijalankan. Rangkuman molekul FQ ke dalam rongga β-CD boleh berlaku melalui dua orientasi iaitu dengan gelang kuinolon (orientasi A) atan gelang piperazina (orientasi C) menghadap rongga β-CD. Kesan pelarut dimodelkan secara implisit menggunakan model kontinuum berkutub (PCM) dalam pengiraan mekanik kuantum dan dengan menggunakan model caj titik mudah (SPC) dalam simulasi dinamik molekul 100 ps. Fluoroquinolones (FQs) is an important group of antibiotics made up of a hydrophobic quinolone and a hydrophilic piperazine rings. Beta-cyclodextrin (β-CD) and its derivatives are currently being widely used in drug delivery systems, owing to its hydrophobic cavities which are capable of forming inclusion complexes with a variety of organic molecules. In this work, the host-guest interactions between FQs and β-CD were investigated using three molecular modelling techniques, i.e. quantum mechanics, molecular docking and molecular dynamics. The penetration of FQ molecules into the β-CD cavity take place via two orientations which are Aorientation with the quinolone ring or C-orientation with the piperazine ring facing towards the β-CD cavity. The effect of solvent was modeled implicitly using polarizable continuum model (PCM) in the quantum mechanics calculation and by simple point charge water model (SPC) in a 100 ps molecular dynamics simulation.