Polyoxygenated Cyclohexenes and Other Constituents of Cleistochlamys kirkii Leaves

Abstract

Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A-F (6-11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15-21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised based on comparison of its NMR spectroscopic features and optical rotation to those of 1, for which the configuration was determined by X-ray diffraction. Observation of the co-occurrence of cyclohexenoids and heptenolides in C. kirkii is of biogenetic and chemotaxonomic significance. Some of the isolated compounds showed activity against Plasmodium falciparum (3D7, Dd2), with IC values of 0.2-40 μM, and against HEK293 mammalian cells (IC 2.7-3.6 μM). While the crude extract was inactive at 100 μg/mL against the MDA-MB-231 triple-negative breast cancer cell line, some of its isolated constituents demonstrated cytotoxic activity with IC values ranging from 0.03-8.2 μM. Compound 1 showed the most potent antiplasmodial (IC 0.2 μM) and cytotoxic (IC 0.03 μM, MDA-MB-231 cell line) activities. None of the compounds investigated exhibited translational inhibitory activity in vitro at 20 μM.

Structure elucidation of cyclohexene (9Z)-octadec-9-enyl ethers isolated from the leaves of Uvaria cherrevensis (Annonaceae)

“…In addition, the coupling constant value between H-2 and H-3 was 3. (Figure 2), isolated from Cleistochlamys kirkii, 13 and so suggests an opposite configuration of the known compound. Therefore, the configuration of cherrevenol M (2) was assigned as 1R,2R,3R,6R.…”

“…(calcd for C34H52O7Na, 595.3611). and 1272 cm −1 ; 1 H NMR (CDCl3, 400 MHz) and 13 C NMR (CDCl3, 125 MHz) data, see Table 2; HRESIMS m/z 657.3770 [M + Na] + (calcd for C39H54O7Na, 657.3767).…”

“…[3][4][5][6][7][8] We report here the first isolation of cyclohexene (9Z)-octadec-9-enyl ethers, cherrevenols M-O (1)(2)(3), from the leaf extracts of U. cherrevensis. The application of 13 C NMR and Ozone Induced Dissociation (OzID) mass spectrometry were used to determine the (Z) configuration and C-9 position of the olefinic moiety of the C-18 ether side chains, respectively.…”

“…The latter would otherwise be difficult to determine because of the lack of 2D NMR correlations due to overlapping of the side chain 1 H and 13 C NMR resonances. The isolated compounds were evaluated for their antimalarial and cytotoxic activities.…”

Review of phytochemistry, biological activities and therapeutic potential of Cleistochlamys kirkii

“…Annonaceae is one of the most diverse and primitive plant families consisting of about 108 genera and 2400 species worldwide (Chatrou et al, 2012;Attiq et al, 2017) argued that members of the Annonaceae family are used throughout the world as sources of traditional medicines used against arthritis, gastrointestinal problems, hypertension, in lammation, respiratory infections, rheumatism, skin infections, snake bites, sores and wounds. The extracts and phytochemical compounds isolated from Annonaceae species are characterized by analgesic, anthelmintic, antidiabetic, anti-in lammatory, antimicrobial, antioxidant, antipyretic, antiulcer, antinociceptive, antimalarial, antiprotozoal, antileishmanial, cytotoxicity and hepatoprotective properties (Bhardwaj et al, 2019) (Bruschi et al, 2011) General weakness Leaf and root decoction taken orally (Bruschi et al, 2011) Haemorrhoid wounds Leaf decoction applied topically (Nyandoro et al, 2017;Kincses et al, 2018) Hernia Leaf and root decoction taken orally (Bruschi et al, 2014;Monjane, 2017)…”