Naural Drug Discovery Flashcards
What are advantages and disadvantages of natural drugs?
Most biologically active natural products are secondary metabolites from plants, microorganisms, marine and animal sources
Advantages: high biological activities
Disadvantages: complex, many chiral centres and functional groups
What is the mode of action of Penicillin?
Penicillin inhibits cross-linking in the bacterial cell wall synthesis - key selectivity originates from L and D isomers of amino acids
What is the mechanism of Penicillin inhibition of transpeptidase?
Penicillin confirmation similar to D-ala-D-ala
Strained beta-lactation ring, CO2 group, carbonyl and amide are essential
Similar structure allows Penicillin to approach and bind, suicide inhibitor forms covalent bond - irreversible inhibition
Why is Penicillin G acid sensitive?
Tertiary amides are usually acid stable, due to the delocalisation of nitrogen (resonance form)
The ring strain of beta-lactam, makes it highly reactive so resonance is not possible and hence, acid labile
What are the SARs of Penicillin and its derivatives?
What are the synthesis options of Penicillin analogues?
Fermentation : only produces limited variations
Chemical synthesis: 6-APA is challenging to produce
Semi-synthesis: combined biochemical transformations
What are three naturally originated beta-lactam antibiotics?
Cephalosporin C
Carbapenems
Clavulanic acid
What were the first-line treatments of malaria?
Quinolines - first-line treatment until wide spread resistance occurred
What is the mode of action of Artemisinin?
Debatable but current understanding is activation by ferrous ions (Fe)
Completely different to quinoline MOA
Endoperoxide bridge essential
Highly reactive radicals generated
Requires activation - pro drug essential
What is a semi-synthetic artemisinin derivative(s) as well as its MOA?
Dihydroartemisinin (R=H)
Artemether (R=Me)
Artesunate - improved solubility
Artemisinin is poorly soluble in water or solvent, the C=O group is not essential for activation
