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Presentation on new generation of antimalarial drugs-1.pptx
1. SEMINAR PRESENTATION
ON
A NEW GENERATION OF ANTIMALARIAL
BY
ADUMATI BOLUWATIFE ELIZABETH
MATRIC NUMBER: 1808010076
DEPARTMENT OF SCIENCE LABORATORY TECHNOLOGY
FACULTY OF SCIENCE
EKITI STATE UNIVERSITY
2. OUTLINES
Introduction
Classification of antimalarial drugs
Need of new AntiMalarials
Some of the New Drug Targets
Future prospects of “covalent bitherapy
Conclusion
3. INTRODUCTION
Malaria is a disease that affects nearly 40% of the global population, and
chemotherapy remains the mainstay of its control strategy.
The global malaria situation is increasingly being exacerbated by the emergence of
drug resistance to most of the available antimalarials, necessitating search for
novel drugs.
A recent rational approach of antimalarial drug design characterized as “covalent
biotherapy”
It involves linking two molecules with individual intrinsic activity into a single
agent.thus packaging dual-activity into a single hybrid molecule
4.
5. Need of new AntiMalarials
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Increasing Resistance
against ACTs
Less treatment
options in malaria
Demand - Supply
imbalance
of Artemisinin
Multiple doses of current
therapy – Non compliance
FDC available in
only some ACTs
Sulfa reactions,
SJS observed with
Sulfadoxine
Fat dependent
bioavailability of
Lumefantrine
New Molecules
are Warranted
Potential Vaccines
in 2025
6. Some of the New Drug Targets
1. Dihydroorotate dehydrogenase (DHODH):
The parasite and mammalian forms differ considerably.
Potent and selective compounds have been developed
2. Adenosine deaminase inhibitors:
3. Purine nucleoside phosphorylase
Inhibitors designed to be active against the transition state of purine nucleoside
phosphorylase have been shown to be active against P. falciparum
Compounds are safe and ready to test on humans
4. Apicoplast – an organelle selectively present in Plasmodium
Metabolic pathways in apicoplast are potential targets
e.g. Fosmidomycin targeting 1-deoxy-d-xylulose 5-phosphate pathway. In Phase – II
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7. Some of the New Drug Targets
5) Protease targets: Are potential but selective parasite selectivity is an issue
e.g. cysteine proteases - falcipain57 and the serine protease inhibitors - PfSUB1
were difficult to develop as drug candidates because of selectivity issues.
6) Choline channel blocker - Albitiazolium bromide. Important because IV/IM
possible and hence can be useful against severe malaria. In Phase II
7) Imidazolopiperazine: In Nov 2011, new class discovered active against both
liver and blood stages of parasite
- Hence, useful to prevent and treat malaria
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8. Future prospects of “covalent bitherapy
Novel antimalarial drugs: The principle of rational drug design of hybrid molecules
Drug-delivery system: to improve drug solubility and stability, and prolong drug release, reduce
doses, dosing intervals, and drug toxicity as well as to achieve targetability
Multiple(compound)-pharmacophoric hybrids e.g., chlorproguanil hydrochloride-dapsone-
artesunate
Tailor-made stage-specific hybrid molecules: have the potential of interrupting malaria
transmission
Elucidation of “drug mechanism of action” as well as “drug-resistance mechanisms
9. Conclusion
The study findings suggest that the current drugs remain effective and that there is
limited importation and establishment of resistant parasites in the area
Hybrid Molecule with dual functionality development and/or multitherapeutic
strategies, which utilize new chemical entities with two (or more) different
heterocyclic skeletons (pharmacophores), represent a valid and rational approach in
design and development of novel antimalarials.
