Supplementary Materials: Evaluation of Cytotoxicity and Α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids
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Supplementary Materials: Evaluation of cytotoxicity and α-glucosidase inhibitory activity of amide and polyamino-derivatives of lupane triterpenoids Oxana B. Kazakova1*, Gul'nara V. Giniyatullina1, Akhat G. Mustafin1, Denis A. Babkov2, Elena V. Sokolova2, Alexander A. Spasov2* 1Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, 71, pr. Oktyabrya, 450054 Ufa, Russian Federation 2Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya st. 39, Volgograd 400087, Russian Federation Correspondence Prof. Dr. Oxana B. Kazakova Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences 71 Prospeсt Oktyabrya Ufa, 450054 Russian Federation E-mail: [email protected] Prof. Dr. Alexander A. Spasov Scientific Center for Innovative Drugs of the Volgograd State Medical University 39 Novorossiyskaya st. Volgograd, 400087 Russian Federation E-mail: [email protected] Figure S1. 1H and 13C of compound 2. H NH N H O H O H 2 2 Figure S2. 1H and 13C of compound 4. NH2 O H O H CH3 O O H H3C O H 4 3 Figure S3. Anticancer screening data of compound 2 at single dose assay 4 Figure S4. Anticancer screening data of compound 7 at single dose assay 5 Figure S5. Anticancer screening data of compound 8 at single dose assay 6 Figure S6. Anticancer screening data of compound 9 at single dose assay 7 Figure S7. Anticancer screening data of compound 12 at single dose assay 8 Figure S8. Anticancer screening data of compound 13 at single dose assay 9 Figure S9. Anticancer screening data of compound 14 at single dose assay 10 Figure S10. Anticancer screening data of compound 15 at single dose assay 11 Figure S11. Anticancer screening data of compound 16 at single dose assay 12 Figure S12. Anticancer screening data of compound 17 at single dose assay 13 Figure S13. Anticancer screening data of compound 19 at single dose assay 14 Figure S14. Anticancer screening data of compound 20 at single dose assay 15 Figure S15. Anticancer screening data of compound 22 at single dose assay 16 Figure S16. Anticancer screening data of compound 24 at single dose assay 17 Figure S17. Anticancer screening data of compound 25 at single dose assay 18 Figure S18. Anticancer screening data of compound 26 at single dose assay 19 Figure S19. Anticancer screening data of compound 4 at single dose assay 20 Figure S20. Anticancer screening data of compound 4 at a 5-dose assay 21 Figure S21. Anticancer screening data of compound 5 at single dose assay 22 Figure S22. Anticancer screening data of compound 5 at a 5-dose assay 23 Figure S23. Anticancer screening data of compound 6 at single dose assay 24 Figure S24. Anticancer screening data of compound 6 at a 5-dose assay 25 Figure S25. Anticancer screening data of compound 10 at single dose assay 26 Figure S26. Anticancer screening data of compound 10 at a 5-dose assay 27 Figure S27. Anticancer screening data of compound 11 at single dose assay 28 Figure S28. Anticancer screening data of compound 11 at a 5-dose assay 29 Figure S29. Anticancer screening data of compound 21 at single dose assay 30 Figure S30. Anticancer screening data of compound 21 at a 5-dose assay 31 Table S1. Gene ontology (GO) term enrichment analysis for compound 4 across the NCI-60 panel cell lines based on CellMiner analysis GO Term P value Adjusted Genes P value1 Biological process – – – – Molecular function – – – – 1 P value was calculated using the hypergeometric test and corrected for multiple hypothesis testing (P <0.05) using the Benjamini-Hochberg false discovery rate (FDR) adjustment. 32 Table S2. Gene ontology (GO) term enrichment analysis for compound 5 across the NCI-60 panel cell lines based on CellMiner analysis GO Term P value Adjusted Genes P value Biological process Central nervous 4.3374E-5 3.5581E-2 RPH3A EMX1 CYP26C1 TLX3 GSX1 HP TBR1 LHX5 system development PTF1A Hindbrain 7.1163E-5 3.5581E-2 HP TBR1 LHX5 PTF1A development Brain development 1.5166E-4 4.2809E-2 RPH3A EMX1 GSX1 HP TBR1 LHX5 PTF1A Multicellular 1.8287E-4 4.2809E-2 TDPX2 HP TNFAIP2 OR1I1 CACNA1F BRS3 RPH3A organismal process RS1 PLAU OBP2B MDK PRDX1 LTA4H DRD4 EMX1 PAQR7 GSX1 OR6J1 LIF TBR1 MMP9 EREG SLC6A5 F7 OR13C8 CYP26C1 TLX3 LHX5 SCN4A PTF1A Neuron differentiation 2.6561E-4 4.2809E-2 EMX1 TLX3 GSX1 LIF TBR1 LHX5 CACNA1F PTF1A Removal of 4.0054E-4 4.2809E-2 TDPX2 PRDX1 superoxide radicals Cellular response to 4.0054E-4 4.2809E-2 TDPX2 PRDX1 superoxide Cellular response to 4.0054E-4 4.2809E-2 TDPX2 PRDX1 oxygen radical System development 4.1848E-4 4.2809E-2 EMX1 GSX1 TDPX2 HP LIF TNFAIP2 TBR1 CACNA1F MMP9 EREG RPH3A F7 CYP26C1 TLX3 PLAU MDK PRDX1 LHX5 LTA4H PTF1A Neuron fate 4.4580E-4 4.2809E-2 TLX3 GSX1 PTF1A commitment Natural killer cell 5.1371E-4 4.2809E-2 TDPX2 PRDX1 mediated immunity Natural killer cell 5.1371E-4 4.2809E-2 TDPX2 PRDX1 mediated cytotoxicity Molecular function Thioredoxin 9.7772E-5 2.4736E-2 TDPX2 PRDX1 peroxidase activity 1 P value was calculated using the hypergeometric test and corrected for multiple hypothesis testing (P <0.05) using the Benjamini-Hochberg false discovery rate (FDR) adjustment. 33 Table S3. Gene ontology (GO) term enrichment analysis for compound 6 across the NCI-60 panel cell lines based on CellMiner analysis GO Term P value Adjusted Genes P value Biological process Immune system 7.4114E-8 1.4037E-4 CX3CR1 CD86 FH CXCL9 SELPLG TNFRSF13B NCF4 process WAS IKZF1 ITGAL IL2RG LY9 CORO1A CTSS CD79A IGKC FLVCR1 IL21R CCR7 S1PR4 CCR2 CCL25 CR2 LY86 THEMIS RHOH CYBB DEFA1 HSH2D POLR3A CD8B IFNG BANK1 KLHL6 POU2AF1 PECAM1 CD28 TLR9 HCLS1 TLR7 DTL MS4A1 PVALB Positive regulation of 3.0981E-6 2.9339E-3 CD86 FH CR2 THEMIS MIA3 IKZF1 CORO1A FCER2 immune system CD79A IFNG KLHL6 CD28 TLR9 CD38 CD37 TLR7 process DTL MS4A1 Immune response 6.4668E-6 4.0827E-3 CX3CR1 CD86 FH CXCL9 NCF4 WAS ITGAL IL2RG LY9 CORO1A CTSS IGKC CCR7 S1PR4 CCR2 CCL25 CR2 LY86 CYBB DEFA1 POLR3A CD8B KLHL6 POU2AF1 CD28 TLR9 TLR7 DTL MS4A1 Leukocyte activation 3.8908E-5 1.8423E-2 CX3CR1 CD86 WAS THEMIS RHOH IKZF1 ITGAL CD79A HSH2D CD8B BANK1 IL21R CD28 TLR7 MS4A1 Lymphocyte activation 5.5271E-5 1.8927E-2 CD86 WAS THEMIS RHOH IKZF1 ITGAL CD79A HSH2D CD8B BANK1 IL21R CD28 MS4A1 Regulation of immune 5.9959E-5 1.8927E-2 CD86 FH CR2 SPI1 TNFRSF13B THEMIS MIA3 IKZF1 system process CORO1A FCER2 CD79A CD8B IFNG KLHL6 CD28 TLR9 CD38 CD37 TLR7 DTL MS4A1 Defense response 1.2927E-4 3.4978E-2 CX3CR1 CD86 FH CXCL9 WAS LSP1 ITGAL PLA2G7 CORO1A CYSLTR1 CCR7 CCR3 CCR2 CCL25 CR2 RNASE6 LY86 CYBB KIR3DL2 DEFA1 POLR3A IFNG TLR9 CARD18 TLR7 MS4A1 Regulation of immune 1.6038E-4 3.7970E-2 CD86 FH CR2 THEMIS FCER2 CD79A CD8B IFNG response KLHL6 CD28 CD37 TLR7 DTL MS4A1 Molecular function Cytokine binding 4.4139E-5 2.4850E-2 CX3CR1 IL10RA TNFRSF18 IL3RA IL21R TNFRSF17 CCR7 IL2RG CCR3 CCR2 1 P value was calculated using the hypergeometric test and corrected for multiple hypothesis testing (P <0.05) using the Benjamini-Hochberg false discovery rate (FDR) adjustment. 34 Table S4. Gene ontology (GO) term enrichment analysis for compound 10 across the NCI-60 panel cell lines based on CellMiner analysis GO Term P value Adjusted P Genes value Biological process Chromatin 2.4288E-6 2.4791E-3 FOXA1 KMT2D SMARCD2 KDM3B KMT2B organization HIST2H2AB YEATS4 HIST2H2AC MBTD1 HIRA VPS72 LEO1 HIST1H2AE SUDS3 ATXN7L3 HIST1H3D BPTF HIST1H2AM SETDB1 KMT5C USP21 SETD1B INO80 HIST2H2BE HIST2H2BD HIST3H2A TADA1 TSSK4 HIST2H3D HIST1H2BC Positive regulation of 3.1487E-6 2.4791E-3 FOXA1 KMT2D KMT2B RAC3 steroid hormone receptor signaling pathway Positive regulation of 3.1487E-6 2.4791E-3 FOXA1 KMT2D KMT2B RAC3 estrogen receptor signaling pathway Regulation of estrogen 4.1174E-5 2.2425E-2 FOXA1 KMT2D KMT2B RAC3 receptor signaling pathway Protein-DNA complex 4.7470E-5 2.2425E-2 HIST1H2AM HIST3H2A HIST2H2AB HIST1H2AE assembly HIST2H3D HIST2H2BE HIST1H3D HIST2H2AC HIST2H2BD PIAS1 HIST1H2BC Nucleosome assembly 9.5898E-5 3.7752E-2 HIST1H2AM HIST3H2A HIST2H2AB HIST1H2AE HIST2H3D HIST2H2BE HIST1H3D HIST2H2AC HIST2H2BD HIST1H2BC Chromatin assembly 1.4443E-4 4.8735E-2 HIST1H2AM HIST3H2A HIST2H2AB HIST1H2AE HIST2H3D HIST2H2BE HIST1H3D HIST2H2AC HIST2H2BD HIST1H2BC Molecular function Binding 1.9603E-5 1.0632E-2 TCERG1 ZNF296 EHF IFITM1 IL1RN NUP107 PGAP2 ACSM3 RPL34 PRF1 CALML4 AQP5 NADSYN1 RPL6 CRKL CCAR1 IKZF5 ZFYVE28 FAM110A PNP RUSC1 RASSF5 CHEK2 MYB OGFOD2 TRIM25 STRA13 KIF21B ZNF721 LGALS9 ZNF720 LGALS8 ATXN7L3 FNBP4 IL15RA AQR ENTPD2 NUP210 RSAD2 SYTL1 COG2 ACSL5 PHKA1 SIGIRR CLDN4 SPINT1 PRKAR1B PPA2 PPA1 ZC3H11A TRIM14 TARS2 DNA2 ATF5 ZNF830 HIST2H3D ZSCAN29 CDS1 CRABP2 GIPR SH2D2A PEX11B STXBP2 GATA2 SAMSN1 ACTR3B MTMR7 MBTD1 APOH INPP5D RDH16 CEP72 GSE1 RIMKLA ZBTB7A NTSR1 HIST1H3D ZRANB3 JUP SETDB1 LRBA SETD1B SIAH2 SH2D1B ABCA7 NBEAL2 PTK6 PYCR2 INO80 TRERF1 UBAC1 GADD45G CDAN1 RPL27A CCDC88C MYO5C MKS1 INTS5 REN DUS1L 35 ZNF138 RPS24 ZNF497 RET DHRS13 SERPINA1 HIST2H2AB ICA1 NAT10 HBB SMG7 PCSK6 ZNF48 HIST2H2AC MMP20 DMBX1 COIL GYS2 TRMT112 ENSA RAC3 JAK3 ZNF485 TIGD3 SERPINB3 UPF2 SERPINB4 PARP4 SIRT7 HEXDC CBFA2T3 SRP9 HIST2H2BE F5 HIST2H2BD MED28 FAHD2B VAMP8 CNKSR1 PSMA3 PDIK1L RPUSD2 DMC1 TUT1 ALDOC GLCCI1 RNF166 DCP2 PDZRN4 ZNF592 RPL10 MRPS31 TUBD1 TANK AKAP1 FGD3 HIRA ADRBK1 LEO1 PLAGL2 RPS2 RPL18 REM2 SPDEF GCH1 F12 CARD9 OSM NR1H3 KLHL3 PUS7L GRHL1 C17ORF62 GRHL2 DEF6 BATF MAS1 TMCO6 KRT19 LRG1 NR6A1 HIST3H2A DHRS9 TTC6 IL17F KBTBD7 FOXA1 DGKE TOR2A ZNF692 STEAP4 PRUNE RORC YEATS4 TSEN2 NPEPPS ZFP36 CAPN8 PPIP5K1 EME2 POGZ ZNF207 HIST1H2AE TNFRSF8 ZNF687 HIST1H2AM ZBP1 TLE3 ZBTB39 CISH KMT5C GTF3A ZBTB32 LMTK3