A cytotoxic triketone–phloroglucinol–bullatenone hybrid from Lophomyrtus bullata

Abstract

Cytotoxic activity against the P388 cell line was seen in a crude extract of the New Zealand shrub Lophomyrtus bullata(Myrtaceae). Bioactivity-guided isolation led to a compound with NMR spectra complicated by the presence of two isomers. These crystallised together and an X-ray structure showed them to be stereoisomeric hybrids of triketone, phloroglucinol and bullatenone units. NMR measurements on the mixed isomers, as well as a cyclic ether produced from them by acid catalysed dehydration, were consistent with these structures. The natural products, named bullataketals A and B, have cytotoxic activity against the P388 cell line (IC(50) 1 microg ml(-1)), and antimicrobial activity against Bacillus subtilis.

Structures and Bioactive Properties of Myrtucommulones and Related Acylphloroglucinols from Myrtaceae

“…Myrtucommulones A and B (1–2), the founder compounds in this review, were preliminarily characterized for their antibiotic activity in agar plate diffusion assays against Gram-positive bacteria, namely Staphylococcus aureus, Staphylococcus epidermidis , Bacillus subtilis, Bacillus pumilus, Enterococcus faecalis, Corynebacterium diphtheriae, and Corynebacterium xerosis [75]. Similar assays provided concurrent indications in this respect for a few more products, such as the bullataketals (8–9) [31], myrtucommulones C–E (10–12) [33], and eucalyptone G (13) [29]. Afterwards, effectiveness against Gram-positive bacteria has been repeatedly reported for other related compounds, and circumstantiated with details concerning their minimum inhibitory (MICs) (Table 3).…”

“…Additional indications concerning the inhibitory effects on tumor cells have resulted in several laboratories from assays that were carried out with a number of compounds of the myrtucommulone series. Particularly, antiproliferative activity has been reported for bullataketals A and B ( 8 – 9 ) on murine leukemia cells (P388) [31], for myrtucommulones A and J ( 1, 21 ) on another prostate cancer cell line (DU145), HEpG2 (human liver carcinoma) and MT-4 (lymphocytic leukemia) [35], on PC3 and DU145 treated with a mixture of 1 and myrtucommulone D ( 11 ) [73], on HCT116 (human colorectal carcinoma) treated with 11 and isomyrtucommulone B ( 5 ) [25], on HeLa (human cervix uteri carcinoma) for tomentodiones S and T ( 60 – 61 ), rhodomyrtone A ( 7 ), and rhodomyrtosones A, B, G, and I ( 18 , 19 , 43 , 22 ) [50].…”

Phloroglucinol derivative MCPP induces cell apoptosis in human colon cancer

“…In example, Rottlerin isolated from Hypericum drummondii have shown cytotoxic activity in human fibrosarcoma [Song et al, 2008]. Bullatenone is a triketone phloroglucinol, the main cytotoxic component compound in Lophomyrtus bullata [Larsen et al, 2005]. Hyperforin, a new lead compound extracts from the herbaceous plant Hypericum perforatum L., has been reported against the progression of cancer in leukemia [Quiney et al, 2006].…”

Native New Zealand plants with inhibitory activity towards Mycobacterium tuberculosis

“…Extracts of Citrus aurantifolia , C. sinensis and Olea europaea were found to be active against both drug-susceptible and drug-resistant strains of virulent M. tuberculosis with minimum inhibitory concentrations of between 0.1 and 0.025 mg/ml [ 19 ]. Although, the New Zealand shrub Lophomyrtus bullata (Ramarama) has been identified as having activity towards Bacillus subtilis [ 20 ], to current knowledge, Pukatea or other New Zealand plants have not been assayed for activity against mycobacteria [ 21 ].…”

“…Bullatenone, discovered in L. bullata (Ramarama), is an antiseptic [ 28 ]. Chemical derivatives of bullatenone have been found to have anti-microbial properties against Bacillus subtilis [ 20 ]. Ngaione, a hepatotoxic sesquiterpene, found in the leaves of M. laetum (Ngaio) has been used in the treatment of athletes foot [ 28 ].…”