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. 2022 Dec 2;27(23):8499.
doi: 10.3390/molecules27238499.

Synthesis, Anti-Influenza H1N1 and Anti-Dengue Activity of A-Ring Modified Oleanonic Acid Polyamine Derivatives

Affiliations

Synthesis, Anti-Influenza H1N1 and Anti-Dengue Activity of A-Ring Modified Oleanonic Acid Polyamine Derivatives

Irina Smirnova et al. Molecules. .

Abstract

A series of sixteen A-ring modified (2,3-indolo-, 2-benzylidene) oleanonic acid derivatives, holding some cyclic amines, linear polyamines and benzylaminocarboxamides at C28, has been synthesized and screened for antiviral activity against influenza A/PuertoRico/8/34 (H1N1) and Dengue virus serotypes of DENV-1, -2, -3, -4. It was found that 28-homopiperazine 2 and 3-N-phthalyl 22 amides of oleanonic acid demonstrated high potency with selectivity index SI 27 (IC50 21 μM) and 42 (IC50 12 μM). Oleanonic acid aminoethylpiperazine amide 6 and C-azepano-erythrodiol 23 appeared to be the most effective compounds against DENV-1 (IC50's 67 and 107 μM) and -2 (IC50's 86 and 68 μM correspondingly) serotypes.

Keywords: Dengue virus; Ugi derivatives; antiviral activity; benzylidene; indole; influenza A (H1N1); oleanolic acid; polyamine; triterpenoids.

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Conflict of interest statement

The authors have declared no conflict of interest.

Figures

Scheme 1
Scheme 1
Reagent and conditions: i. a. (COCl)2, Et3N, CH2Cl2, 25 °C; b. gomopiperazine (for A), spermine (for B), spermidine (for C), diethylentriamine (for D), or aminoethylpiperazine (for E), Et3N, CH2Cl2, reflux; ii. PhNHNH2, AcOH, reflux; iii. BnNH2, paraform, CNCH2COOEt, 25 °C; PhNHNH2, AcOH, reflux; iv. ClCH2CN, K2CO3, DMF, reflux; v. NaN3, NH4Cl, DMF, reflux.
Scheme 2
Scheme 2
Reagent and conditions: i aldehydes, 40%KOH/EtOH, EtOH, 22 °C, ii. NaBH4, MeOH, 25 °C; iii. a. (COCl)2, Et3N, CH2Cl2, 25 °C; b. gomopiperazine (for A), spermine (for B), Et3N, CH2Cl2, reflux; iv. NH4OAc, NaBH3CN, MeOH, 22 °C; v. phthalic anhydride, DCC, DMAP, CH2Cl2, 0 °C; vi. a. NaBH4, MeOH, rt; b. AcCl, pyridine, reflux; c. O3, CH2Cl2, −40 °C; d. NH2OH∙HCl, pyridine, reflux 4 h; e. SOCl2, 1,4-dioxane, 22 °C, 30 min; f. LiAlH4, 1,4-dioxane, reflux, 14 h.

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