Citral is well known for its antimicrobial, antifungal, and insecticidal activities. Natural sesquiterpene α-methylenelactones also exhibit a broad spectrum of biological activities. The aim of the study was to explore the effect of structural changes to citral molecules on citral behavior-modifying activity towards Myzus persicae. Specifically, the effects of the introduction of a γ-lactone moiety and methylene groups in α and γ positions of the lactone ring were investigated. The lactones were obtained in five-step (saturated lactone and γ-methylenelactone) or six-step (α-methylenelactone and α,γ-dimethylenelactone) syntheses from citral. The synthetic procedures and physical and spectral data of the lactones are presented. The settling behavior of freely moving aphids in choice and no-choice situations was monitored. The probing behavior of tethered M. persicae using the Electrical Penetration Graph (EPG) technique was also analyzed. Citral appeared a strong repellent and pre-ingestive and ingestive probing deterrent to M. persicae. The incorporation of a lactone moiety caused the loss of the repellent activity. α-Methylenelactone inhibited aphid settling and probing activities at pre-ingestive and ingestive phases. The saturated γ-lactone and α,γ-dimethylenelactone were the settling post-ingestive deterrents to M. persicae, which did not affect aphid probing activity. γ-Methylenelactone did not affect aphid behavior.

Six γ-oxa-ε-lactones, 4-phenyl-3,4-dihydro-2H-1,5-benzodioxepin-2-one (5a) and its five derivatives with methoxy groups in different positions of A and B rings (5b–f), were synthesized from corresponding flavanones. Three of the obtained lactones (5b,c,f) have not been previously described in the literature. Structures of all synthesized compounds were confirmed by complete spectroscopic analysis with the assignments of signals on ¹H and ¹³C-NMR spectra to the corresponding atoms. In most cases, lactones 5a–f exerted an inhibitory effect on the growth of selected pathogenic bacteria (Escherichia coli, Bacillus subtilis, and Staphylococcus aureus), filamentous fungi (Fusarium graminearum, Aspergillus niger, and Alternaria sp.), and yeast (Candida albicans). The broadest spectrum of activity was observed for unsubstituted lactone 5a, which was particularly active against filamentous fungi and yeast. Lactones with methoxy groups in the 3′ (5c) and 4′ (5d) position of B ring were more active towards bacteria whereas lactone substituted in the 7 position of the A ring (5e) exhibited higher antifungal activity. In most cases, the introduction of lactone function increased the activity of the compound compared to its flavonoid precursors, chalcones 3a–e, and flavanones 4a–f.

Thujone is a natural biologically active monoterpene ketone component of essential oils of numerous plants. The aim of the study was to evaluate the effect of β-thujone and β-thujone derivatives bisulfite adduct, lactone, oxime, and lactam application on behavior of Myzus persicae (Sulz.) (Hemiptera: Aphididae) during probing and settling. The choice and no-choice tests (aphid settling and Electrical Penetration Graph (EPG), respectively) revealed that stereochemistry of thujone was important for biological activity (β-thujone caused changes in aphid behavior while α-thujone did not) and that cyclopentane ring modifications and functional groups addition gave derivatives that possessed stronger and more durable deterrent effects. The most effective modification was the incorporation of a lactam moiety into the β-thujone molecule. Application of β-thujone lactam limited aphid settling for at least 24 h, caused restlessness in aphids and a delay or failure in reaching phloem phase by M. persicae. β-Thujone lactam can be considered a deterrent of medium potency with activity expressed at preingestive phase of aphid probing. Other compounds did not restrain aphid stylet penetration in non-phloem tissues but slightly limited sap ingestion (lactone, oxime), and restrained aphid settling for a period of less than 24 h (β-Thujone, bisulphite adduct, lactone).

In this study, novel phosphatidylcholines containing ibuprofen or naproxen moieties were synthesized in good yields and high purities. Under the given synthesis conditions, the attached drug moieties racemized, which resulted in the formation of phospholipid diastereomers. The comperative studies of the cytotoxicity of ibuprofen, naproxen and their phosphatidylcholine derivatives against human promyelocytic leukemia HL-60, human colon carcinoma Caco-2, and porcine epithelial intestinal IPEC-J2 cells were carried out. The results of these studies indicated that phospholipids with NSAIDs at bothsn-1 andsn-2 positions (15 and 16) were more toxic than ibuprofen or naproxen themselves, whereas 2-lysophosphatidylcholines (7 and 8) were less toxic against all tested cell lines. Phospholipids with NSAIDs atsn-1 and palmitic acid atsn-2 (9 and 10) were also less toxic against Caco-2 and normal cells (IPEC-J2).

Four compounds with lactone moiety were synthesized from chalcone 1 in three- or four-step synthesis. γ-Bromo-δ-lactone 5 was the only product of bromolactonization of acid 4 whereas bromolactonization of ester 3, apart from lactone 5 also afforded its isomer 6 and two diastereoisomeric δ-hydroxy-γ-lactones 7 and 8. Lactone 8 was also obtained in 88% yield as a product of simultaneous dehalogenation and translactonization of γ-bromo-δ-lactone 5 by Penicillum frequentans AM 359. Chalcone-derived lactones 5–8 were subjected to the tests on antimicrobial activity and the results compared with activity of starting chalcone 1. Obtained lactones 5–8 in most cases limited the growth of tested bacterial and fungal strains. The highest activity was found for δ-hydroxy-γ-lactone 8 which completely inhibited the growth of Staphylococcus aureus, Fusarium graminearum, Aspergillus niger, and Alternaria sp. The introduction of lactone moiety into chalcone scaffold significantly improved antimicrobial activity of the compound: γ-bromo-δ-lactone 6 and δ-hydroxy-γ-lactone 8 were significantly stronger growth inhibitors of S. aureus and F. graminearum. In the case of the latter, a clear positive effect of the lactone function on the antifungal activity was also observed for γ-bromo-δ-lactone 5.

Background: The study investigated four flavanone-derived γ-oxa-ε-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2′, 4′ and 8. Our objective was to find out if the introduction of the methoxy group into the aromatic ring affects in vitro anti-tumor potency of the investigated lactones. Methods: Cytotoxic and pro-apoptotic effects were assessed with cytometric tests with propidium iodide, annexin V, and Western blot techniques. We also investigated potential synergistic potency of the tested lactones and glucocorticoids in canine lymphoma/leukemia cell lines. Results: The tested flavanone-derived lactones showed anti-cancer activity in vitro. Depending on its location, the methoxy group either increased or decreased cytotoxicity of the derivatives as compared with the parent compound. The most potent lactone was the one with the methoxy group at position 4′ of the B ring (compound 3), and the weakest activity was observed when the group was located at C-8 in the A ring. A combination of the lactones with glucocorticoids confirmed their synergy in anti-tumor activity in vitro. Conclusions: Methoxy-substituted flavanone-derived lactones effectively kill canine lymphoma/leukemia cells in vitro and, thanks to their synergistic action with glucocorticoids, may potentially be applied in the treatment of hematopoietic cancers.