uggesting that the sites of substituents on the benzene ringalso affect the antibacterial activity.
This is something similar to what I have done in my research lab. We synthesize Bafetinib analogues and are working to probe the effect that one specific nitrogen has on immuno-activity. More specifically the effect of cytokine production and inhibition.
As shown in Figure 8, the oxygen atom in the nitro group of5c formed a hydrogen bond with N−H on residue U2564, andthe carbonyl group at position C-21 formed a hydrogen bondwith residue G2044. Moreover, residue G2484 formed ahydrogen bond with the carbonyl group on the parent ring ofpleuromutilin. Compound 6j formed two hydrogen bonds withresidue G2044 via the carbonyl group at the C-21 side chain,whereas residue G2484 formed a hydrogen bond with thecarbonyl group at the C-3 position of the pleuromutilin parentring. Residue U2046 also formed a hydrogen bond with NH2in the purine. The carbonyl groups at the C-3 and C-21positions of 8a formed hydrogen bonds with the residuesG2044 and G2484, respectively. Furthermore, U2564 inter-acted with the purine ring via a hydrogen bond.
What are the thermodynamic and kinetic parameters (e.g., binding affinities, dissociation constants, or activation energies) of the interactions between the thioguanine-modified pleuromutilin derivatives (i.e. compound 6j) and the bacterial ribosome's 50S subunit? This question is left unanswered because quantitative data elating to thermodynamic and kinetic parameters is not discussed.
Existingresearch suggests that the presence of purine groups in theC-14 side chain of pleuromutilin derivatives can increase theirantibacterial activity.28,2
The presence of purine groups in the C-14 side chain of pleuromutilin derivatives increase their antibacterial activity by inhibiting protein synthesis. This occurs because the purine groups react really well with the 50S ribosomal subunit in bacteria. The ring structure of purine and the basic nature of the nitrogen atoms within it allow for stronger hydrogen bonding and electrostatic interactions with the ribosome, which leads to increased binding affinity and a more potent inhibitory effect. Additionally, the presence of purine groups may also contribute to improved water solubility and bioavailability of the drug.