Pharmacological Potential of Lathyrane-Type Diterpenoids from Phytochemical Sources

Abstract

Lathyrane diterpenoids are one of the primary types of secondary metabolites present in the genus Euphorbia and one of the largest groups of diterpenes. They are characterized by having a highly oxygenated tricyclic system of 5, 11 and 3 members. These natural products and some synthetic derivatives have shown numerous interesting biological activities with clinical potential against various diseases, such as cytotoxic activity against cancer cell lines, multi-drug resistance reversal, antiviral properties, anti-inflammatory activity and their capability to induce proliferation or differentiation into neurons of neural progenitor cells. The structure of the lathyrane skeleton could be considered privileged because its framework is able to direct functional groups in a well-defined space. The favorable arrangement of these makes interaction possible with more than one target. This review aims to highlight the evidence of lathyranes as privileged structures in medicinal chemistry. Chemical structures of bioactive compounds, the evaluation of biological properties of natural and semisynthetic derivatives, and the exploration of the mechanisms of action as well as target identification and some aspects of their targeted delivery are discussed.

Biological Properties of Latex, Aqueous Extracts and Bee Products of Euphorbia officinarum L.: A Short Review

“…Further, those ingol diterpenoids underwent redox, etherification and esterification modifications of the 5- and 11-membered rings ( Figure 3 ). The presence of the phenylacetyl group is also frequent in lathyrane diterpenoids [ 34 ].…”

“…Although the biological properties of those lathyrane diterpenes have not been evaluated, Vela et al [ 34 ] in their review work noted that terpenes belonging to this group have biological properties with clinical potential (cytotoxicity, multidrug resistant reversal ability, antiviral and anti-inflammatory properties, and capability to induce neural progenitor cell proliferation or differentiation into neurons).…”

Rapid Access to Tigliane, Ingenane, and Rhamnofolane Diterpenes from a Lathyrane Precursor via Biomimetic Skeleton Transformation Strategy

“…It is of note that lathyranes, as one of the largest groups in macrocyclic diterpenes, are easily available plant-derived natural products. 5 Lathyrane-type Euphorbia factor L 3 (1) is the main component of the seeds of E. lathyris, the average content of which in E. lathyris is about 5 g/kg based on plant dry weight. Furthermore, Euphorbia factor L 3 had a flexible undecane ring that is well suited to being a synthetic precursor for chemical conversion into other diterpene types.…”

“…and polycyclic (tigliane, ingenane, rhamnofolane, daphnane, premyrsinane, etc.) cores. , Biologically, the structural diversity of Euphorbia diterpenes is responsible for their various biological activities including antiproliferative, antiviral, and anti-inflammatory properties. , Among the bioactive Euphorbia diterpenes, ingenol mebutate, a ingenane-type diterpene, was approved by FDA in 2012 for the treatment of actinic keratosis . The daphnane-type diterpene resiniferatoxin acts as a nonopioid analgesic to relieve cancer pain and is undergoing clinical trials .…”

Brønsted Acid-Mediated Conversion of Naturally Abundant Lathyrane Diterpenes: Are Rare 10,11-seco-Lathyrane Diterpenes Artifacts?

“…Euphorbia diterpenes, a class of structurally diverse natural products, are the main active constituents from the genus Euphorbia (Euphorbiaceae). − Compounds of this family display interesting biological activities closely associated with human health, including cytotoxic, , anti-inflammatory, , and multidrug-resistance-reversing properties. , Two specific examples are the notable PKC regulator ingenol mebutate and the TRPV1 receptor agonist resiniferatoxin . Structurally, they present the vast chemical diversity by means of varying macrocyclic or polycyclic ring systems along with varying levels of oxidation and acylation .…”