Relationship between 13C NMR Parameters and Antimalarial activity of Cryptolepine Isosteres

Density functional theory calculations were applied to investigate 13C Chemical Shielding (CS) tensors in cryptolepine (1) and its sulfur (2) and oxygen (3) isosteres. The results showed that the CS of carbon nuclei in these compounds may be divided into three types. First, carbons type α, are those directly bonded to X (X= NH, S, O) and σ33 shielding component of these carbons are deshielded in O isostere compared to N and S isosteres. The second group of carbons (β carbons) is attached to α-carbons, in which σ11 components of S isostere differs from O and N isosteres. The third carbon group, γ-carbons are positioned at a distance of three interatomic bonds or greater away from X. The replacement of N by O or S in cryptolepine isosteres has negligible influence on all components of the later carbon type. The variations of CS components could be related to the inactivity of O isostere and broad spectrum activity of S isostere.