ORIGINAL PAPER New mirsinane-type diterpenes from Euphorbia microsciadia Boiss. with inhibitory effect on VEGF-induced angiogenesis Syed Mustafa Ghanadian • Abdul Majid Ayatollahi • Suleiman Afsharypuor • Shaghayegh Haghjooy Javanmard • Nasim Dana Received: 27 December 2011 / Accepted: 24 June 2012 Ó The Japanese Society of Pharmacognosy and Springer 2012 Abstract Euphorbia microsciadia (Euphorbiaceae) is a perennial plant growing in Iran. Two new cyclomyrsinol esters, 3-O-propionyl-5, 10, 14-O-triacetyl-8-O-(2 0 -methyl- butanoyl)-cyclomyrsinol (1) and 3, 5, 10, 14, 15-O-penta- acetyl-8-O-isobutanoyl-cyclomyrsinol (2) were isolated from the methanolic extract of its dried aerial parts. The structures were elucidated based on 13 C- and 1 H-NMR as well as 2D-NMR, IR and different MS spectra. Anti- angiogenic activity was also evaluated on vascular endo- thelium growth factor (VEGF)-induced angiogenesis in cultured human umbilical vein endothelial cells in vitro by assessing capillary-like tube network formation. Keywords Euphorbia microsciadia  Myrsinane diterpenoid  Anti-angiogenesis activity Introduction Natural products continue to play an important role in the discovery of new pharmaceuticals. In this connection, certain types of diterpenes in genus Euphorbia have very interesting immunomodulatory and anti-tumor properties [1, 2]. The genus Euphorbia has been used in Iranian tra- ditional medicine in the treatment of gout and back pain, and as a paste on sores [3]. Using 1 H-NMR-guided frac- tionation, two diterpenoids structurally related to cyclom- yrsinols were isolated, and we report here their structural elucidation along with their anti-angiogenetic activity using a standard matrigel angiogenesis assay (Fig. 1). Our rational for this assay was a recent report on cheiradone—a myrsinane type diterpenoid—as a potent vascular endo- thelial growth factor receptor antagonist [4]. However, it is the first time that a cyclomyrsinol diterpene is reported as an inhibitor of angiogenesis and, therefore, Euphorbia microsciadia could be a natural source of this chemo-type for treatment of diseases associated with pathological angiogenesis such as cancer and diabetic eye diseases [5]. Results and discussion Compound 1 has the molecular formula C 34 H 48 O 13 according to HRESI-MS (m/z 687.2980 [M ? Na ? ], calc. 687.2987). The IR spectrum of 1 confirmed presence of free hydroxyl group (3522 cm -1 ), carbonyl (1737 cm -1 ) and C–O functions (1147–1022 cm -1 ) with no absorption of olefinic group. Three singlet methyl protons d H 1.89 s, 2.08 s and 2.14 s with HMBC cross links with esteric carbonyl carbons and sequential loss of 60 amu indicated the presence of three acetate groups [6]. In addition, EI-MS peaks at m/z 591[M-73], along with 13 C- and 1 H-NMR S. M. Ghanadian Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran A. M. Ayatollahi (&) Phytochemistry Research Center, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran e-mail: phytochemistry.center@gmail.com S. Afsharypuor Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran S. H. Javanmard  N. Dana Physiology Research Center, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran 123 J Nat Med DOI 10.1007/s11418-012-0686-3