Cytotoxicity against HL60 Cells of Ficifolidione Derivatives with Methyl, n-Pentyl, and n-Heptyl Groups

Abstract

Ficifolidione, a natural insecticidal compound isolated from the essential oils of Myetaceae species, is a spiro phloroglucinol with an isobutyl group at the C-4 position. We found that ficifolidione showed cytotoxicity against cancer cells via apoptosis. Replacement of the isobutyl group by n-propyl group did not influence the potency, but the effect of the replacement of this group by a shorter or longer alkyl group on the biological activity remains unknown. In this study, ficifolidione derivatives with alkyl groups such as methyl, n-pentyl, and n-heptyl group—instead of the isobutyl group at the C-4 position—were synthesized to evaluate their cytotoxicity against the human promyelocytic leukaemia cell line HL60 and their insecticidal activity against mosquito larvae. The biological activities of their corresponding 4-epimers were also evaluated. As a result, the conversion of the isobutyl group to another alkyl group did not significantly influence the cytotoxicity or insecticidal activity. In HL60 cells treated with the n-heptyl-ficifolidione derivative, the activation of caspase 3/7 and the early stages of apoptosis were detected by using immunofluorescence and flow cytometric techniques, respectively, suggesting that the cytotoxicity should be induced by apoptosis even though the alkyl group was changed.

Spiro Derivatives in the Discovery of New Pesticides: A Research Review

“…According to the literature summary, the introduction of active spirocyclic structures into neonicotinoid compounds, indole compounds, and natural products improves their insecticidal activities against Lepidoptera , Hemiptera , and Diptera insects and other pests. − Neonicotinoids are currently the most widely used insecticides. They act on nicotinic acetylcholine receptors in the insect’s nervous system and peripheral nerves, causing paralysis. , These compounds are highly efficient and selective broad spectrum insecticides.…”

“…However, a series of derivatives from 51 (ficifolidione), a natural insecticidal compound containing short and long alkyl substituted isobutyl groups, exhibited no obvious insecticidal activity against Culex pipiens pallens , indicating that the alkyl length had no effect on biological activity. But, these compounds are highly cytotoxic to human promyelocytic leukemia cells (HL60) . Matrine is a natural plant pesticide and a broad-spectrum insecticide exhibiting contact and gastric toxicity, but its efficiency is lower than other pesticides.…”

Recent Developments in Photocatalytic Reduction of Nitro Compounds to Valuable Scaffolds

“…In organic synthesis the utilization of these compounds has been remarkable due to their unique chemical behavior. 1 2 In the last two decades these compounds have been imperative for the construction of scaffolds for drugs, dyes, explosives, agrochemicals, polymers, etc . 3 The nitro group is highly electron withdrawing in chemical nature hence it decreases the electron density on framework of scaffolds and activates the adjacent α-hydrogen as well as adjacent C–C double and triple bonds.…”