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 (IC_50′s 67 and 107 μM) and -2 (IC_50′s 86 and 68 μM correspondingly) serotypes.

Novel diterpenic peptide derivatives were synthesized via the Ugi four-component reaction at ambient temperature. The protocol employed a reaction between formaldehyde, benzyl amine, the corresponding diterpene acid, and ethyl 2-isocyanoacetate. The anticancer properties of the compounds were studied in vitro.

Natural compounds, including diterpenoids, play a critical role in various biological processes and are recognized as valuable components in cancer treatment. Isocyanides multicomponent reactions (IsMCRs) are one of the effective methods to obtain adducts at the carboxyl group with a peptide-like substituent. In this study, dehydroabietic acid and levopimaric acid diene adducts as the starting scaffolds were modified by the multicomponent Passerini (P-3CR) and Ugi (U-4CR) reactions to afford α-acyloxycarboxamides and α-acylaminocarboxamides. A group of twenty novel diterpene hybrids was subjected to NCI in vitro assessment, and a consistent structure–activity relationship was established. Eleven of the synthesized derivatives inhibited the growth of cancer cells of 4 to 39 cell lines in one dose assay, and the most active were derivatives 3d, 9d, and 10d holding a fragment of 1a,4a-dehydroquinopimaric acid. They were selected for a five-dose analysis and demonstrated a significant antiproliferative effect towards human cancer cell lines. The outstanding cytotoxic activity was observed for the P-3CR product 3d with growth inhibitory at submicromolar and micromolar concentrations (GI₅₀ = 0.42–3 μM) against the most sensitive cell lines. The U-4CR products 9d and 10d showed selective activity against all leukemia cell lines with GI₅₀ in the range of 1–17 µM and selectivity indexes of 5.49 and 4.72, respectively. Matrix COMPARE analysis using the GI₅₀ vector showed a moderate positive correlation of compound 3d with standard anticancer agents that can influence kinase receptors and epidermal growth factor receptors (EGFRs). The ADMET analysis acknowledges the favorable prognosis using compounds as potential anticancer agents. The obtained results indicate that these new hybrids could be useful for the further development of anticancer drugs, and 1a,4a-dehydroquinopimaric acid derivatives could be recommended for in-depth studies and the synthesis of new antitumor analogs on their basis.

The azido-Ugi reaction of methyl maleopimarate N-(2- aminoethyl) imide with isocyanides, paraformaldehyde and trimethylsilyl azide in one step leads to 1,5-disubstituted diterpene bis-tetrazoles. The compounds demonstrate selective cytotoxicity against NCI-60 cancer cell panel.