Synthesis and biological activity of mono- and diamides of 2,3-secotriterpene acids

Abstract

Four types of amide (C3; C28; C3-C28) conjugates based on 2,3-seco-18alphaH-oleanane and 2,3-secolupane mono- and dicarboxylic acids were synthesized. The range of diamide derivatives was supplemented with C3-C3' and C28-C28' dicondensed amides with two A-secotriterpene backbones educed by reacting monocarboxylic A-secoacids with biogenic amino acid lysine. Compounds with inhibitory action against herpes virus reproduction (EC50 8.7 and 4.1 McM) were found among the synthesized mono- and diamide derivatives containing an ethyl-beta-alaninate fragment. It has been ascertained that diamide with ethyl-beta-alaninate fragment combines anti-herpes virus properties and anti-HIV activity (EC50 5.1 McM). For active compounds, the maximum non-toxic concentration (MNTC)/EC50 ratios ranges from 9.7 to 40.8. The synthesized amide conjugates do not exhibit any marked cytotoxic effects against human tumor cell lines rabdomiosarcoma RD TE32, A549 lung carcinoma and melanoma MS.

Azepanodipterocarpol is potential candidate for inhibits influenza H1N1 type among other lupane, oleanane, and dammarane A-ring amino-triterpenoids

“…A lupane 2,3-seco aldehydoacid, diacid, 3-aldoxime derivatives can suppress the reproduction of HSV-1 and Flu A (EC 50 from 0.06 to 21.3 μM) [35,36]. Ethyl β-alaninate diamide 2,3 seco-lupane was shown to combine antiherpetic (EC 50 4.1 μM) and anti-HIV activity (EC 50 5.1 μM) [37] and C-28 amide conjugate with a 2aminpropane-1,3-diol was the most active compound against herpes simplex virus type I (5.7 μM, MTC/EC 50 32.2) [38]. Inhibition of the serotype A viruses with a protection index of 60% by 2,3-and 3,4-seco-dammarane acids was reported in [39].…”

“…Earlier, examples of the high antiviral activity of triterpenoid seco derivatives are presented [34][35][36][37][38][39]. Unfortunately, in contrast to the above data, 3,4-seco-3-aminoderivatives 16-19 were practically inactive against Flu A with SI values from 1 to 3.…”

Recent advances in natural anti‐HIV triterpenoids and analogs

“…Two A‐secolupane derivatives ( 65 and 66 ; Figure 9) showed weak inhibitory activity against HIV‐1 PR (IC 50 = 15.7 and 25.4 μM, respectively) 67 . In another report, the synthesis and evaluation of anti‐HIV activity of mono‐ and diamides of 2,3‐secolupane acids were reported, and Compound 67 (Figure 10) showed anti‐HIV activity 68 . Lupane triterpene oximes ( 68 and 69 ; Figure 11) were synthesized using oxonitrile recyclization and the ThorpeeZiegler cyclization.…”

“…67 In another report, the synthesis and evaluation of anti-HIV activity of mono-and diamides of 2,3-secolupane acids were reported, and Compound 67 ( Figure 10) showed anti-HIV activity. 68 Lupane triterpene oximes (68 and 69; Figure 11) were synthesized using oxonitrile recyclization and the Compounds 70-75 (Table 1 and Figure 12) showed a wide arrange of inhibitory activity. 70 Recently, six novel lupane-type C-3 triterpenones with C-28 heterocyclic moieties were synthesized.…”