Synthesis of Nerol Derivatives Containing a 1,2,3-Triazole Moiety and Evaluation of Their Activities against Cancer Cell Lines

Abstract

In the present investigation, a collection of twenty two nerol derivatives, containing 1,2,3-triazolic appendages, was synthesized and screened in vitro for their cytotoxic activity against HL60, Nalm6, and Jurkat human leukemia cells as well as against B16F10 (melanoma cell line). In most cases, derivatives were able to reduce cell viability. The most potent compound (Z)-4-(((3,7-dimethylocta-2,6-dien-1-yl)oxy)methyl)-1-(4-(trifluoromethoxy)benzyl)-1H-1,2,3 triazole showed antiproliferative activity against Jurkat cells and reduced B16F10 cell migration. Physicochemical properties of the compounds were calculated in order to evaluate their potential for drug development. Most of the evaluated physicochemical parameters seemed to be favorable for drug development. In addition, for a better understanding of the biological activity results, 3D quantitative structure-activity relationship (QSAR) studies were carried out. 3D-QSAR studies indicate that the anticancer activities observed for the cell lines HL60 and Jurkat may occur by a similar mechanism of action and the same was found for the Nalm6 and B16F10 cell lines.

1,2,3- Triazoles: general and key synthetic strategies

“…Synthesis of functionalized pyrimidines containing the 1H-1,2,3-triazole ring. 122 Another study involving the use of the Cu(II)/NaAsc catalytic system was reported by Teixeira et al in 2019, 123 in which the authors prepared a series of 1,2,3-triazole compounds from the natural product nerol (Scheme 20). Most compounds showed activity against HL60 human leukemic cells, as well as B16F10 cell lines.…”

“…Synthesis of 1H-1,2,3-triazole derivatives from the natural product Nerol. 123 One of the most positive points of the Cu (II)/NaAsc system is that it is compatible with both oxygen and water, not requiring anhydrous solvents or inert atmosphere. However, Cu(I) residue is cytotoxic and can bind to the active site of many enzymes, blocking or reducing their biological activity.…”

Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against the Leishmania braziliensis Species

“…In this study, a series of twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments were synthesized. Previous investigations conducted by our research group have identified various bioactive compounds containing benzyl groups with different substitution patterns, linked to 1,2,3-triazolyl moieties [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Additionally, the combination of cinnamic acid with benzylated 1,2,3-triazolyl fragments resulted in compounds with significant antileishmanial effect on L. braziliensis [ 27 ].…”

“…In this study, a series of twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments were synthesized. Previous investigations conducted by our research group have identified various bioactive compounds containing benzyl groups with different substitution patterns, linked to 1,2,3-triazolyl moieties [20][21][22][23][24][25][26]. Addition- Natural products are a valuable resource when exploring therapeutic agents, including for the treatment of leishmaniasis [15].…”