Two novel structural types of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors with hexahydroisobenzofuran 11 and 3-oxabicyclo [3.3.1]nonane 12 scaffolds were discovered. These monoterpene-derived compounds were synthesized through preliminary isomerization of (+)-3-carene to (+)-2-carene followed by reaction with heteroaromatic aldehydes. All the compounds inhibit the TDP1 enzyme at micro- and submicromolar levels, with the most potent compound having an IC₅₀ value of 0.65 μM. TDP1 is an important DNA repair enzyme and a promising target for the development of new chemosensitizing agents. A panel of isogenic clones of the HEK293FT cell line knockout for the TDP1 gene was created using the CRISPR-Cas9 system. Cytotoxic effects of topotecan (Tpc) and non-cytotoxic compounds of the new structures were investigated separately and jointly in the TDP1 gene knockout cells. For two TDP1 inhibitors, 11h and 12k, a synergistic effect was observed with Tpc in the HEK293FT cells but was not found in TDP1 −/− cells. Thus, it is likely that the synergistic effect is caused by inhibition of TDP1. Synergy was also found for 11h in other cancer cell lines. Thus, sensitizing cancer cells using a non-cytotoxic drug can enhance the efficacy of currently used pharmaceuticals and, concomitantly, reduce toxic side effects.

The article deals with the effect of the conditions of modification of a natural aluminosilicate catalyst with a 10% HCl solution on the chemical and phase compositions, porous and crystal structures, and acidity of the material and on its catalytic properties in α-pinene isomerization. Treatment of the aluminosilicate with 10% HCl (25–250 mL per gram of solid) causes cation exchange, increases the concentration of protonic sites on the aluminosilicate surface, and removes impurity calcite and dolomite. The specific surface area of the aluminosilicate increases from 52 to 68–82 m²/g. Treatment of the aluminosilicate with 175.0 or 250.0 mL/g of HCl removes a considerable amount framework Al³⁺, Fe^2+/3+, and Mg²⁺ cations, leading to a partial disruption of its structure and to a decrease in its acidity, specific surface area, and, as a consequence, catalytic activity relative to the same parameters of the samples treated with 50 or 100 mL/g of HCl. The highest catalytic activity is displayed by the aluminosilicate treated with 50 mL/g of HCl. The camphene and dipentene selectivity of the reaction (at 85% α-pinene conversion) with the original catalyst is 55 and 30%, respectively; modifying the aluminosilicate with HCl raises the camphene selectivity and reduces the dipentene selectivity by 5–6%. The catalyst considered here is more active than the commercial titanium catalyst.

The development of highly efficient methods for the synthesis of chemical products by using renewable raw materials is one of the topical areas of medicinal chemistry. The paper presents the synthesis of (2aR,2a¹S,5aR,9bR)-4-isopropyl-7,8-dimethoxy-2a¹-methyl-2,2a,2a¹,3,5a,9b-hexahydrofluoreno[9,1-bc]furan. The title compound was obtained through Prins–Friedel–Crafts cascade reactions of trans-4-hydroxymethyl-2-carene, which was synthesized from 3-carene, one of the main components of gum turpentine. The product yield after purification was 48%. The compound’s structure was confirmed by X-ray diffraction analysis.