Betulin derivatives containing a 1,2,3-triazole ring possess a wide spectrum of biological activities, including antiviral, anticancer, and antibacterial activity. A series of novel triazoles were prepared by the 1,3-dipolar cycloaddition reaction between the alkyne derivatives of betulin and organic azides. The chemical structures of the obtained compounds were defined by ¹H and ¹³C NMR, IR, and high-resolution mass spectrometry (HR-MS) analysis. The target triazoles were screened for their antiviral activity against DNA and RNA viruses. The cytotoxic activity of the obtained compounds 5a–k and 6a–h was determined using five human cancer cell lines (T47D, MCF-7, SNB-19, Colo-829, and C-32) by a WST-1 assay. The bistriazole 6b displayed a promising IC₅₀ value (0.05 μM) against the human ductal carcinoma T47D (500-fold higher potency than cisplatin). The microdilution method was applied for an evaluation of the antimicrobial activity of all of the compounds. The triazole 5e containing a 3′-deoxythymidine-5′-yl moiety exhibited antibacterial activity against two gram-negative bacteria vz. Klebsiella pneumoniae and Escherichia coli (minimal inhibitory concentration (MIC) range of 0.95–1.95 μM).

A key parameter in the design of new active compounds is lipophilicity, which influences the solubility and permeability through membranes. Lipophilicity affects the pharmacodynamic and toxicological profiles of compounds. These parameters can be determined experimentally or by using different calculation methods. The aim of the research was to determine the lipophilicity of betulin triazole derivatives with attached 1,4-quinone using thin layer chromatography in a reverse phase system and a computer program to calculate its theoretical model. The physiochemical and pharmacokinetic properties were also determined by computer programs. For all obtained parameters, the similarity analysis and multilinear regression were determined. The analyses showed that there is a relationship between structure and properties under study. The molecular docking study showed that betulin triazole derivatives with attached 1,4-quinone could inhibit selected SARS-CoV-2 proteins. The MLR regression showed that there is a correlation between affinity scoring values (ΔG) and the physicochemical properties of the tested compounds.

The CuAAC reaction of azides and acetylenic triterpenes was used for synthesis of new triazoles of 3-acetylbetulin and betulone. The triazole derivatives were evaluated for their anticancer activity in vitro against amelanotic melanoma C-32, ductal carcinoma T47D and glioblastoma SNB-19 cell lines. 28-[1-(3’-Deoxythymidine-5’-yl)-1H-1,2,3-triazol-4-yl]carbonylbetulone 6e exhibited a significant IC₅₀ value (0.17 µM) against the human glioblastoma SNB-19 cell line, an almost 5-fold higher potency while compared with reference cisplatin.

Betulin 1 and its semisynthetic derivatives exhibit a cytotoxic activity toward various cancer cell lines. These compounds are a promising and potential anticancer candidates. A series of betulin derivatives was prepared and tested for the antiproliferative activity in vitro against T47D breast cancer, CCRF/CEM leukemia, HL-60 promyelocytic leukemia, SW707 colorectal, murine P388 leukemia, as well as BALB3T3 normal fibroblasts cell lines. Cisplatin and betulin 1 were used as a reference compounds. Some derivatives of betulin showed a higher cytotoxic activity than the parent compound 1. Two derivatives (5 and 17) were 24-fold potent than betulin 1 against the human promyelocytic leukemia cell line (HL-60), with an IC₅₀ value of 0.3 µg/mL.

Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification of products as E and Z isomers has been carried out using ¹H-, ¹³C-, ³¹P-NMR, and crystallographic analysis. The crystal structure in the orthorhombic space group and analysis of crystal packing contacts for 29-diethoxyphosphoryl-28-cyclopropylpropynoyloxy-lup-20E(29)-en-3β-ol 8a are reported. All new compounds were tested in vitro for their antiproliferative activity against human T47D (breast cancer), SNB-19 (glioblastoma), and C32 (melanoma) cell lines.

Natural 5,8-quinolinedione antibiotics exhibit a broad spectrum of activities including anticancer, antibacterial, antifungal, and antimalarial activities. The structure–activity research showed that the 5,8-quinolinedione scaffold is responsible for its biological effect. The subject of this review report is a presentation of the pharmacological activity of synthetic 5,8-quinolinedione compounds containing different groups at C-6 and/or C-7 positions. The relationship between the activity and the mechanism of action is included if these data have been included in the original literature. The review mostly covers the period between 2000 and 2019. Previously published literature data were used to present historical points.