Modified cowpea mosaic virus as a carrier of antimalarial drugs

Al-Refai'a, Rana

Chemistry
June 2018

Thesis or dissertation


Rights
© 2018 Rana Al-Refai'a. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

Plant viruses provide exceptional advantages in the field of nanotechnology as multifunctional nanoparticles. Cowpea mosaic virus (CPMV) is being developed as a carrier vehicle for chemotherapeutic drugs. The ability to modify the amine groups on the external capsid surface with three different new chloroquinoline derivatives, and together with sugar, has been demonstrated. Additionally, addressable carboxylates on the external capsid surface have been modified with ferrocene to produce a multifunctional drug carrier.

The redox-active ferrocene on the outer surface of the unmodified and modified CPMV with each chloroquinoline derivative are electrochemically independent. The ability of binding ferrocene to modified and unmodified CPMV as a first or second conjugated compound has been confirmed.

The effectivity of chloroquinoline-derivatives, with and without conjugation to CPMV, has been investigated by beta-haematin inhibition in vitro and in vivo using P. falciparum strain.

(7-chloroquinolin-4-yl) alanine has shown a significant effect as an antimalarial compound after conjugation with CPMV compared to the other chloroquinoline derivatives. This conjugate led to a 90% inhibition of beta-haematin or haemozoin formation, which is necessary for the parasite to survive.

The significance of modified CPMV as a carrier is discussed in relation to developing novel strategies to solve the problem of chloroquine resistant.

The activities of ferrocene in vitro after conjugation to the external surface of CPMV particle was evaluated against P. falciparum strain resulting in a, surprisingly, high kill effect. The IC₅₀ values for conjugated (7-chloroquinolin-4-yl) alanine and conjugated ferrocene were 0.275 nM and 0.309 nM respectively compared to a range from 7.8-10 nM for control chloroquine.

Overall CPMV plays an important role in increasing the effectiveness of (7-chloroquinolin-4-yl) alanine and ferrocene as an antimalarial drugs compared to unconjugated compounds.

Publisher
School of Mathematics and Physical Sciences, The University of Hull
Supervisor
Evans, David J. (Chemist)
Sponsor (Organisation)
Iraq. Wizarat al-Ta'lim al-'Ali wa-al-Baht h al-'Ilmi; Jāmiʻat Bābil
Qualification level
Doctoral
Qualification name
PhD
Language
English
Extent
9 MB
Identifier
hull:17722
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