On the Active Principles of the Spurge Family (Euphorbiaceae) XI. [1] The Skin Irritant and Tumor Promoting Diterpene Esters of Euphorbia tirucalli L. Originating from South Africa

Abstract

The irritant and tum or-prom oting constituents o f latex of Euphorbia tirucalli L. originating from South Africa were isolated. They were identified as irritant ingenane and tigliane type diterpene esters derived from unsaturated aliphatic acids and acetic acid and the polyfunctional diterpene parent alcohols 4-deoxyphorbol, phorbol and ingenol, respectively. The irritant and tum or-prom oting esters of 4-deoxyphorbol are predominant and were fully characterized chem ically and biologically. They are positionally isomeric 12,13-acylates, acetates e.g. Euphorbiafactors T i,-Ti4. A s acyl groups they carry hom ologous, highly unsaturated alipha tic acids o f the general structure C H 3 -(C H 2)m -(CH = CH)" -CO O H (m = 2,4; « = 1,2, 3,4,5; N = 2n + m + 2). C orresponding diesters o f 4-deoxy-4a-phorbol are also present which are biologi cally inactive. Com parison o f structures and biological activities o f 12,13-diesters o f 4-deoxyphorbol indicates that -for a distinct total number o f C-atoms (N) in the acyl m oiety -an increasing number of conjugated double bonds (n) may increase the irritant but decrease the tum or-prom ot ing activity. R eplacem ent o f the hydroxyl function at C-4 (phorbol-12,13-diesters) by hydrogen (corresponding 4-deoxyphorbol-12,13-diesters) does not essentially alter biological activities. Epim erization o f 4-deoxyphorbol-12,13-diesters at C-4 abolishes biological activities.The specific chem ical properties dem onstrated for the diterpene ester irritants contained in the latex o f E. tirucalli and hence in all plant parts may be useful in trials to abolish the potential risk of cancer involved especially in occupational mass production and handling o f the plant. Som e of the structure activity relations o f the Euphorbia factors isolated made them excellent tools in experim ental cancer research for the analysis o f mechanisms of tum origenesis.

Eutirucallin, a RIP-2 Type Lectin from the Latex of Euphorbia tirucalli L. Presents Proinflammatory Properties

“…Species of the genus Euphorbia (Euphorbiaceae) usually present a series of bioactive components as an example of essential oils (eugenol), aldehydes, latex, starch, tigliane-type diterpenes (phorbol esters) and ingenane (ingenol esters), tigliane-type diterpenoids (formaldehyde), lysozymes, and lectins [1], [2], [3]. The Euphorbia tirucalli is origin in Africa and has acclimated to warm places of Brazil, especially in the northeast.…”

“…This plant has been widely used in the practice of alternative medicine due to its wide variety of bioactive molecular constituents. Its latex is highly viscous, toxic and irritating when in contact with the skin or mucosa [2] and provide a molluscicidal activity [4], as well as larvicidal [5] and antitumor activities [6]. In addition, to the latex stimulated myelopoiesis, lead to increase of tumor resistance in mice with EAT (Ehrlich ascites tumor) [7]; and promote a negative effect of the lytic cycle activation of the Epstein-Barr virus [8].…”

Euphorbia tirucalli L. modulates myelopoiesis and enhances the resistance of tumour-bearing mice

“…This plant displays a diverse range of bioactive constituents including the isoeuphorol triterpenoic (C 10 H 50 O), taraxasterol (C 30 H 50 OCH 30 H), tirucallol (C 30 H 50 O), phorbol, ingenane, togliane and diterpenic acid derivatives [1].…”

LC-MS2-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity

“…In particular tigliane-type esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA) (13), phorbol-12,13-didecanoate (11) and prostratin (21), were found to be potent and selective inhibitors of CHIKV (and HIV) replication in vitro [10,11]. TPA, along with other phorbol esters, are known to possess pro-inflammatory and tumor-promoting activities [12][13][14][15] through broad activation of PKCs (Protein kinase C isoenzymes), which makes them unsuitable as antiviral drugs for clinical use [16,17].…”