Pentacyclic triterpenoids, as important representatives of natural products, have garnered widespread attention due to their diverse biological activities, including anti-inflammatory, antiviral, and antitumor effects. Oleanolic acid (OA), betulinic acid (BA), ursolic acid (UA), triptolide, and glycyrrhetinic acid (GA) are typical examples of pentacyclic triterpenoids. Despite their significant biological activities, their poor water solubility and low bioavailability have limited further development and application. In recent years, researchers have developed a series of derivatives with enhanced biological activities and improved drug properties through structural modifications of these compounds, particularly achieving notable progress in the field of antitumor therapy. This review summarizes recent advances in the structural modification of pentacyclic triterpenoids and explores their promising applications in the development of antitumor, antiviral, and other therapeutic agents.

A series of novel derivatives of 18β-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using ¹H NMR, ¹³C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC₅₀ value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC₅₀ value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC₅₀ value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics.

This study focuses on the synthesis of novel vinpocetine derivatives (2–25) and their biological evaluation. The chemical structures of the synthesized compounds were fully characterized using techniques such as ¹H NMR, ¹³C NMR, and HRMS. The inhibitory activity of the synthesized compounds on PDE1A was evaluated, and the results revealed that compounds 3, 4, 5, 12, 14, 21, and 25 exhibited superior inhibitory activity compared to vinpocetine. Compound 4, with a para-methylphenyl substitution, showed a 5-fold improvement in inhibitory activity with an IC₅₀ value of 3.53 ± 0.25 μM. Additionally, compound 25, with 3-chlorothiazole substitution, displayed an 8-fold increase in inhibitory activity compared to vinpocetine (IC₅₀ = 2.08 ± 0.16 μM). Molecular docking studies were conducted to understand the binding models of compounds 4 and 25 within the active site of PDE1A. The molecular docking study revealed additional binding interactions, such as π–π stacking and hydrogen bonding, contributing to the enhanced inhibitory activity and stability of the ligand–protein complexes. Overall, the synthesized vinpocetine derivatives demonstrated promising inhibitory activity on PDE1A, and the molecular docking studies provided insights into their binding modes, supporting further development of these compounds as potential candidates for drug research and development.

Isosteviol and its derivatives, diterpene compounds with a wide range of biological activities, play important antiviral, antibacterial, antioxidant, antitumor, analgesic, anti-inflammatory, antipyretic, antifungal, and anticardiovascular disease roles. Because of its unique diterpene skeleton, isosteviol is frequently used as an active framework in drug synthesis, thus helping medicinal chemists design highly selective, potentially active, and multifunctional isosteviol analogs for the treatment of various diseases. In recent years, rapid developments in the design and synthesis of isosteviol derivatives have proven effective and important in the field of medicinal chemistry research. This article briefly reviews the novel derivatives obtained through structural modification of isosteviol, including their pharmacological activities, to provide a reference for the development of new synthetic strategies and the construction of new isosteviol derivatives, and to guide preclinical studies and development of new drugs with greater pharmacological efficacy.

C₁₁H₁₂BrNO₂, monoclinic, P2₁/n (no. 14), a = 7.5143(12) Å, b = 11.8968(15) Å, c = 12.9852(13) Å, β = 105.575(14)°, V = 1118.2(3) ų, Z = 4, R _gt (F) = 0.0607, wR _ref (F ²) = 0.1615, T = 293.00(10) K.