Bioorganic Chemistry

Experiments represented in Fig. 2 are the molecular docking of ITH12680 with PP2A enzyme (Computational Medicinal Chemistry) Experiments represented in Fig. 3 are the PP2A activity in presence of ITH12680 and its selective inhibitor okadaic acid (protein serine-threonine phosphatase) Experiments represented in Fig. 4 show the effect of ITH12680 on the cell viability of A549 NSLC cells, compared with fingolimod (Cytotoxicity) Experiments represented in Fig. 5 show the apoptotic capacity of cisplatin on A549 NSLC cells, compromised by nicotine, in presence or abscence of ITH12680 (apoptosis) Experiments represented in Fig. 6 show the regulation of survival and proapoptotic phosphoproteins mediated by PP2A reactivation (Western-blot) Experiments represented in Fig. 7 show the effect of ITH12680 in the PP2A endogenous inhibitors expression (Western-blot)

Supplementary Information: IR, H & C NMR, MS data

The 1H and 13C NMR spectra of the title compounds.

Structural Characterization data of synthesized derivatives

This data file describe the synthesis of 2'-deoxyadenosine analogues with 6-substituents, and its application in the optimization of 8-17 and 17E DNAzymes, more efficient DNAzymes with Ca2+-preference was achieved.

Supplementary data for “Synthesis and biological evaluation of 2-epi-jaspine B analogs as selective sphingosine kinase 1 inhibitors”

A series of nineteen nitrogen-containing lupane triterpenoids was obtained by modification of C2, C3, C20 and C28 positions of betulonic acid and their α-glucosidase inhibiting activity was investigated. Being a leader compound from our previous study, 2,3-indolo-betulinic acid was used as the main template for different modifications at C-(28)-carboxyl group to obtain cyano-, methylcyanoethoxy-, propargyloxy- and carboxamide derivatives. 20-Oxo- and 29-hydroxy-20-oxo-30-nor-analogues of 2,3-indolo-betulinic acid were synthesized by ozonolysis of betulonic acid followed by Fischer indolization reaction. To compare the influence of the fused indole or the seven membered A-ring on the inhibitory activity, lupane A-azepanones with different substituents at C28 were synthesized. The structure-activity relationships revealed that the enzyme inhibition activity dramatically increased (up to 4730 times) when the carboxylic group of 2,3-indolo-betulinic acid was сonverted to the corresponding amide. Thus, the IC50 values for glycine amide and L-phenylalanine amides were 0.04 and 0.05 μM, respectively. This study also revealed that 2,3-indolo-platanic acid is 4.5 times more active than the parent triterpenoid with IC50 of 0.4 μM. Molecular modeling suggested that improved potency is due to additional polar interactions formed between C28 side chain and a sub-pocket of the α-glucosidase allosteric site.

2D NMR data of compound 12. 1H NMR and 13C NMR of compound 12

It is the original FID files of the synthesized compounds

The HRESIMS, UV, 1D and 2D NMR of compounds 1-6 are available in the supplementary data.