Supplementary Material (ESI) for Natural Product Reports This journal is The Royal Society of Chemistry Effect on promastigotes, amastigotes of

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1 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Table 2. Biological activities of purely synthetic guanidines Entry Guanidine compound Biological activity Potency Ref F 3 C 2 2 CF PFF2 and PFF1 inhibitor pec ± 0.2 (PFF1) pec ± 0.4 (PFF2) PFF2 and PFF1 inhibitor pec 50 nd (PFF1) pec ± 0.2 (PFF2) PFF2 and PFF1 inhibitor pec 50 < 5.5 (PFF1) pec ± 0.2 (PFF2) 2 wild-type Leishmania donovani and Effect on promastigotes, amastigotes of macrophage cell line C on-peptidic substrate-mimetic inhibitors of Akt IC 50 ) 36 ± 7.0 μm (promastigotes) (IC 50 ) 9 ± 1.0 μm (amastigotes) (IC 50 ) 12 ± 2 μm 28 C 6 2 C Activities of the prepared compounds at the h4r in the steady-state GTPase assay (pec 50 ) Inhibition of cathepsin G 15,600 k obs /I b (M -1 s -1 ) 30 P 8 Ac-Phe-Val-Thr-Phg P (4- guanidine)-(c Me) 2 Inhibition of cathepsin G 256,000 k obs /I b (M s -1 ) 9 2 Antihyperglycemic and food intakereducing agent Reductions of glycemia levels at IT and of cumulative water (- 59 %) and food (- 40 %) intake, after 5 d of treatment in Male db/db Mice 31

2 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Table 2. (contd.) Biological activities of purely synthetic guanidines Entry Guanidine compound Biological activity Potency Ref Affinity (pki) of 4 receptor ligands at rat histamine receptors Rat : pk i 6.9 ± 0.1 uman: pk i 7.5 ± Anti-mycobacterial activity against. aureus MIC 7.8 μg/ml 33 L Fmoc D-Arg. 13 C 2 In vitro antitrypanosomal activity IC 50 (T. brucei rhodesiense TIB900 strain) μm C 2 In vitro antiplasmodial activity IC 50 (P. falciparum K1 2 strain) μm () 2 Binding affinities to I 1, I 2 and α 2 - adrenoceptors I 1 IC nm; I 2 K i 54,950 nm; α 2 K i 11,770 nm Br 16 R 2 Inhibition of [ 125 I]-echistatin specific binding to purified human integrin proteins α v β 3 and α v β 5 IC 50 (α v β 5 ) 21.0 ± 2.1; IC 50 (α v β 3 ) 32.6 ± 7.0; Two-site model, α v β 3 : IC 50h 6.5 ± 2.0 and IC 50l 458 ± 191 (IC 50h and IC 50l correspond to IC 50 in the receptor high- and low affinity states) PY Y 1 R antagonism on EL cells (calcium assay) and Y 1 R binding determined on K--MC cells Y 1 R antagonism (Ca 2+ - assay) K b 7.0 ± 2.5 nm Effects of amino acid mutations of Loop 2 B, C and E residues on 5-T (serotonin) and mcpbg (m-clorophenylbiguanidine) induced functional response mcpbg EC ±

3 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Entr y Guanidine compound Biological activity Potency Ref i-bu Inhibition in human CXCR4 transfected Chinese hamster ovary (C) cells using [ 125 I]DF-1 as a radioligand IC μm Ar et 2. Binding affinities and an antagonistic response at the 5- T6 receptor K i 1.6 ± 0.1 nm; I max 157 ± 6 (%); IC ± 9 nm C C 6 5 istamine 2 receptor agonism on the guinea pig right atrium pec ± C C 3 C 6 11 Agonist efficacies and potencies at h 2 R Gsα and gp2r Gsα expressed in f9 cell membranes h 2 R Gsα EC ± 1.1 nm C 3 C 6 11 Agonist efficacies and potencies at h 2 R Gsα and gp2r Gsα expressed in f9 cell membranes gp 2 R Gsα EC ± 1.1 nm Ph 2 Antibacterial against various human pathogenic taphylococci MIC 0.5 μg/ml C 2 Activity at recombinant ρ1 GABA C receptors expressed in Xenopus oocytes IC μm CF 3 Inhibition of the root-growth of rape (Brassica campestris) 86.7 % at 100 μg/ml 44 C Binding assays in human prefrontal cortex to determine agonistic or antagonistic activity in vitro functional [35]GTPγ EC ± 18 μm 45

4 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Entry Guanidine compound Biological activity Potency Ref [ 3 C 3 ] 2 E-1 inhibitor (IC 50 ) PK1 receptor antagonists (IC 50 ) Me 2 Antidiabetic agent 69 μm (I.V.) 0.1 mm (oral) elective anti-protozoal activity against trypanosomes (EC 50 ) Antifungal activity (MIC) Antifungal activity (MIC) 32 µg/ml C 3 C 3 C C 34 C uman histamine 4 receptor ligand (h 4 R agonist) (pec 50 ) Me Peptide-mimetic antagonists (IC 75 ) Me 2

5 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Entry Guanidine compound Biological activity Potency Ref Maize polyamine oxidase (PA) inhibitor (K i ) 0.08 nm C Factor Xa inhibitor (IC 50 ) 6 nm 55 Ph 38 2 IAG- inhibitory activity (K i ) 7.0 ± F F F C 2 Thrombin inhibitor (K i ) 1.2 nm C 3 5-T 5A /5-T 7 receptor ligand (K i ) 1.3 nm P B (C 3) 2 Induces dystrophin expression 6 mg/kg (Intravenous dose) 59 B {(C 2) 2C[(C 2) 6C 2] 2} 2 {(C 2) 2C[(C 2) 6C 2] 2} 2 43 Br β-secretase inhibitor (BACE-1) (IC 50 )

6 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Entry tructure Biological activity Potency Ref. 44 istamine 2 -receptor agonist (pec 50 ) 7.80± ± Acid-sensing ion channel-3 inhibitor (IC 50 ) (AIC3) AIC3 titration Antiproliferative activity (IC 50) 1.9 KBR C 2 CF i inhibitor (K i ) 10.5 ± istone deacetylase inhibitor (IC 50 ) 14 nm DAC 1/ istone deacetylase inhibitor (IC 50 ) 4.7 ± 0.2 DAC (IC 50 ) 1.3 ± 0.7 DAC3 2 2

7 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Entry tructure Biological activity Potency Ref. 50 Me Me 2 a + / + exchanger inhibitor (IC 50 ) 3.60 nm Me 2 51 Br Cholera toxin inhibitor (IC 50 ) 31 ± i inhibitor (IC 50 ) C 2 2 euraminidase inhibitor (IC 50 ) CC 3 54 Me Me Me 2 Apoptosis inducer (EC 50 ) ± Caspase activation activity (GI 50 ) ± cell growth inhibition FXa inhibitor (IC 50 ) 9 nm (EC 2xPT ) 2.5 μm Inducing weight loss in mice ± 1.0 (BALB/c) ± 0.7 (ob/ob) ± 0.8 (DI)

8 upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Entry tructure Biological activity Potency Ref. 57 EaC blocker (IC 50 ) 7.54 ± 2.71 nm CBE (IC 50 ) 6.40 ± 5.93 nm BE