New Antimycobacterial and Antimalarial 8,9-Secokaurane Diterpenes from Croton kongensis

Abstract

Two new 8,9-secokaurane diterpenes, ent-8,9-seco-7alpha,11beta-diacetoxykaura-8(14),16-dien-9,15-dione (1) and ent-8,9-seco-8,14-epoxy-7alpha-hydroxy-11beta-acetoxy-16-kauren-9,15-dione (2), together with two known compounds, ent-8,9-seco-7alpha-hydroxy-11beta-acetoxykaura-8(14),16-dien-9,15-dione (3) and ent-7beta-hydroxy-15-oxokaur-16-en-18-yl acetate, were isolated from Croton kongensis. This is the first report on the presence of 8,9-secokauranes in the plant genus Croton. Diterpenes 1-3 exhibited antimycobacterial activity with minimum inhibitory concentrations (MICs) of 25.0, 6.25, and 6.25 microg/mL, respectively, and possessed antimalarial activity with IC(50) ranges of 1.0-2.8 microg/mL. They also demonstrated comparable cytotoxicity toward the Vero (IC(50) ranged from 0.9 to 3.2 microg/mL), KB (IC(50) from 1.2 to 13.8 microg/mL), and BC cell lines (IC(50) from 1.1 to 2.2 microg/mL, except for compound 1, which was inactive against BC cells).

Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae)

“…It is frequently used in folk medicine for dysmenorrhoea. 38 C. oblongifolius Roxb., popularly known as "chucka", is a middle-sized tree and grows in India and Thailand. The leaves are used as tonic, the flowers against flat worms, the fruits to treat dysmenorrhoea, the seeds as purgative, 39 the bark to treat dyspepsia and the roots to treat dysentery.…”

“…38 Plaunotol (5) has exhibited activity against twenty methicillin-resistant and fourteen methicillin-sensitive strains of Staphylococcus aureus. 187,188 The results suggested that plaunotol might be useful in the prevention of infection and skin care for patients with atopic dermatitis.…”

Oxidant effects and toxicity ofCroton campestrisinDrosophila melanogaster

“…(Euphorbiaceae) (Campos et al 2002;Almeida et al 2003;Rosa et al 2003), antimicrobial and the antimalarial effects Croton kongensis Gagnep. (Thongtan et al 2003), antinociceptive and anti-inflammatory properties of Croton malambo Karst. (Su arez et al 2003).…”

Synthesis and antituberculosis activity of derivatives of the diterpenoid isosteviol with azine, hydrazide, and hydrazone moieties

“…Increasing the number of methylenes in the spacer from one to eight decreases MIC from 25 to 12.5 Pg/mL [18]. These results were unusual because 1, its bis-derivatives [18], and the aforementioned di-and triterpenoids of different structures [4,5,[8][9][10][11][12][13][14][15][16][17] are not nitrogenous organic compounds yet they exhibit antituberculosis activity at the level of the N-containing antituberculosis drug pyrazinamide (MIC = 12.5 Pg/mL) [19,20]. This is probably evidence that they have a different mechanism of M. tuberculosis growth inhibition.…”

“…All other tuberculosis drugs [1] and agents undergoing preclinical and clinical trials [2,3] are products from organic syntheses. Nevertheless, over 50 metabolites of various structures that inhibit the growth of Mycobacterium tuberculosis in the range of minimum inhibiting concentrations (MIC) 60-3 Pg/mL have currently been isolated from natural plant sources [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Diterpenoids [4,5,[8][9][10][11][12][13] and triterpenoids [4,5,11,[14][15][16][17] are most widely represented among them.…”