Search Results (4)

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. Full article

The application of isocyanide-based multicomponent reactions (IMCRs) for triterpenoid functionalization has been little reported. Triterpenoids and their derivatives are an important class of natural products of interest in medicinal chemistry due to their potential applications as antibacterial, antifungal, and cytotoxic agents. Herein, we describe the use of ethanol as a solvent in the Passerini reaction for the functionalization of masticadienonic acid isolated from fruits and peduncles of P. mexicana. A small series of α-acyloxycarboxamides was synthesized with moderate to good overall yields of 33 to 57%, evaluating and extending the scope of the aldehyde component. Full article

The application of immobilized sulfuric acid on silica gel (H₂SO₄-SiO₂) as an efficient and easily reusable solid catalyst was explored in the synthesis of novel α-acyloxycarboxamide derivatives via a Passerini reaction of benzoic acid, aldehyde/ketone, and isocyanides. The Passerini adducts were obtained in high to excellent yields within 10 min in aqueous media under catalytic conditions. The key advantages of the process include a short reaction time, high yields, the catalyst’s low cost, and the catalyst’s reusability. Full article

Herein we describe the synthesis of a small series of α-acyloxycarboxamides via a facile and efficient one-pot procedure, employing a plant-derived triterpenoid as carboxylic acid component. The products were obtained in overall yields of 25 to 79%, while we scoped the effect of the nature of the aldehyde component on the reaction yields. Full article