Limonene and Perillyl Alcohol Derivatives: Synthesis and Anticancer Activity

Abstract

: Limonene and perillyl alcohol are natural monoterpenes that have attracted the attention of medicinal chemists due to their promising anticancer activities. Considering this, both compounds were explored as scaffolds to obtain various derivatives with anticancer activity. In this review, the data are organized for the first time, with a focus on the synthetic methods and strategies to obtain the derivatives, throughout the period from 2000 to 2020. A brief discussion regarding the structure and activity relationships of the most active derivatives, stereoisomers and their mechanisms of action is presented. Among the active compounds, a series of limonenes with thiosemicarbazone groups and perillyl alcohol hybrids with glycosides or drugs are illustrated. Taking all of this into account, this review may help researchers develop new promising anticancer candidates based on the structures of limonene and perillyl alcohol.

A descriptive review on exploiting the therapeutic significance of essential oils as a potential nutraceutical and food preservative

“…EOs obtained from numerous plants have shown to possess anticancer properties against oral, breast, lung, liver, colon, prostate, and brain cancers, as well as leukemia (Andrade et al., 2018). This is not only applicable to EOs but also their compounds like citral (Bailly, 2020), dlimonene, perillyl alcohol (POH) (da Silva et al., 2021), carvacrol (Jayakumar et al., 2012; Yazici et al., 2021) , myrcene, and α thymol (Deb et al., 2011; Pincigher et al., 2023). Anticancer activity of EOs is given in Table 1.…”

A straightforward access to trifluoromethylated natural products through late-stage functionalization

“…Perillyl alcohol is able to serve as a healing agent for anticancer therapeutics. 116 In addition, Ir-photoredox catalysts are also capable of catalyzing the trifluoromethylation of estrone derivatives, cholestanol, and vitamin E derivative, proceeding analogous catalytic cycles under light irradiation. 117–124…”

Changes in the serum metabolomic profiles of subjects with NAFLD in response to n-3 PUFAs and phytosterol ester: a double-blind randomized controlled trial

“…36 Perillyl alcohol is not produced by itself in the human body; it is a common compound that is naturally found in some foods, especially as a metabolite of limonene, which can be found in many foods and drinks (as a food additive or common component in food). 46 A study showed that limonene is metabolized by the p450 enzyme cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and CYP2C19 to its metabolite perillyl alcohol in human liver microsomes. 47 The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.…”