Novel tetrahydrofuran derivatives from Trigonostemon howii with their potential anti-HIV-1 activities

A novel tetrahydrofuran derivative, trigonohowine (1), together with five known tetrahydrofuran derivatives (2–6), were isolated from the stems and leaves of Trigonostemon howii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. Among them, trigonohowine (1) represents the first example of a new type of tetrahydrofuran derivative, possessing an unprecedented carbon skeleton containing 23 carbon atoms on the carbon skeleton and the known compouds (2–6) are rare tetrahydrofuran derivatives in the plant kingdom with various carbon skeletons. All isolated compounds were evaluated for their anti-HIV-1 activities. Compounds 1–6 showed significant anti-HIV-1 activities with EC₅₀ ranged from 0.08 to 1.03 µM. These findings suggest that the discoveries of these tetrahydrofuran derivatives with significant anti-HIV-1 activities isolated from T. howii could be of great importance to the development of new anti-HIV agents.     

A new polyacetylenic fatty acid and other secondary metabolites from the Chinese green alga Caulerpa racemosa (Caulerpaceae) and their chemotaxonomic significance

A new polyacetylenic fatty acid, (8E,12Z,15Z)-10-hydroxy-8,12,15-octadecatrien-4,6-diynoic acid (1), together with five known metabolites, including two linear diterpenes (3 and 4) and three sterols (5–7), has been isolated from the Chinese green alga Caulerpa racemosa. Its structure was determined on the basis of extensive spectroscopic analysis. Compound 1 represents the first example of polyacetylenic lipids from marine algae up to now, while compound 4 is characterized for the first time in the Caulerpaceae. Furthermore, the chemotaxonomic significance of these compounds was also summarized.     

Anti-microfouling properties of compounds isolated from several Mediterranean Dictyota spp.

Brown algae of the genus Dictyota are widespread around the world and are common along the coasts of the Mediterranean Sea. These marine organisms keep their surface relatively free from biofouling and are known for their ability to produce a wide array of bioactive compounds, mostly diterpenes, whose ecological functions are not clearly defined. In this study, an evaluation of the chemodiversity of the Dictyota genus was conducted on three samples, harvested on both NW and SW Mediterranean coasts (France and Algeria, respectively). Ten compounds were purified from the organic extracts of these samples; their chemical structures were elucidated by 1D and 2D NMR spectroscopy and were compared with literature data. Among them, three new diterpenes [one dolabellane (1), one xenicane (2), and one prenylated guaiane (3)] were characterized together with five previously described compounds [3,4-epoxy-14-oxo-7,18-dolabelladiene (4), acetoxycrenulide (5), dictyol E (6), 10,18-dihydroxydolabella-2,7-diene (7), and 10-acetoxy-18-hydroxydolabella-2,7-diene (8)]. In addition, the occurrence of two known glycerol derivatives [1-Ο-octadecenoylglycerol (9) and sn-3-Ο-(geranylgeranyl)glycerol (10)] was also determined. Some of the isolated compounds (4–6 and 8–10) were screened for their potential to prevent the adhesion of three bacterial strains isolated from marine biofilms in comparison with four commercial antifoulants (TBTO, Zineb, ZnPT, and CuPT): those bearing a glycerol moiety (compounds 9 and 10) exhibited the strongest anti-adhesion effects, whatever the strain, and with a moderate toxicity. Thus, these chemical structures should be further explored for both their putative involvement in keeping the algal surface free of biofouling and the development of effective and environmentally benign antifoulants.     

Solution- and solid-phase synthesis and anti-HIV activity of maslinic acid derivatives containing amino acids and peptides

Maslinic acid (1) has been coupled at C-28 with several α- and ω-amino acids by using solution- and solid-phase synthetic procedures. Twelve derivatives (2–13) with a single amino acid residue were prepared in solution phase, whereas a dipeptide (14), a tripeptide (15), and a series of conjugate dipeptides (16–24) were synthesized in solid phase. The anti-HIV activity of these compounds was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as a reporter. While in maslinic acid (1) were present both cytotoxic and antiviral activities, only the derivatives 13 and 24 showed anti-HIV-1 activity and therefore represent a novel class of anti-HIV-1 compounds.     

Evaluation of in vitro anticancer activity of sphaeropsidins A–C,fungal rearranged pimarane diterpenes,and semisynthetic derivatives

Sphaeropsidins A (1), B (7) and C (10), three fungal phytotoxins, unrearranged pimarane diterpenes produced by Diplodia cupressi and 10 semisynthetic derivatives were evaluated for their in vitro anticancer activities. Among these 13 compounds, sphaeropsidin A and two derivatives (2 and 6) thereof display 50% growth-inhibitory concentration in the low micromolar range for all cell lines analyzed. Structure activity relationship paralleled the phytopathogenic and antimicrobial ones except regarding the vinyl group at C-13 that does not seems to be required as it is for their antipathogenic activity.     

Bioactive secondary metabolites from the marine-associated fungus Aspergillus terreus

Three new compounds, including a prenylated tryptophan derivative, luteoride E (1), a butenolide derivative, versicolactone G (2), and a linear aliphatic alcohol, (3E,7E)-4,8-dimethyl-undecane-3,7-diene-1,11-diol (3), together with nine known compounds (4–12), were isolated and identified from a coral-associated fungus Aspergillus terreus. Their structures were elucidated by HRESIMS, one- and two-dimensional NMR analysis, and the absolute configuration of 2 was determined by comparison of its electronic circular dichroism (ECD) spectrum with the literature. Structurally, compound 1 featured an unusual (E)-oxime group, which occurred rarely in natural products. Compounds 1–3 were evaluated for the α-glucosidase inhibitory activity, and compound 2 showed potent inhibitory potency with IC₅₀ value of 104.8 ± 9.5 μM, which was lower than the positive control acarbose (IC₅₀ = 154.7 ± 8.1 µM). Additionally, all the isolated compounds were evaluated for the anti-inflammatory activity against NO production, and compounds 1–3, 5–7, and 10 showed significant inhibitory potency with IC₅₀ values ranging from 5.48 to 29.34 μM.     

Chemical constituents from the roots of Euphorbia nematocypha Hand.-Mazz.

A new myrsinol-type diterpene (1), three myrsinol-type diterpenes (2–4), three ent-abietane-type diterpenes (5–7), one tigliane-type diterpene (8), two cycloartane-type triterpenes (9–10), and two tirucallane-type triterpenes (11–12) were isolated from the roots of Euphorbia nematocypha Hand.-Mazz. Their structures were identified by spectroscopic analyses and by comparison of their spectral data with those reported in the literature. Compound 12 was isolated and reported from plants for the first time. All compounds were isolated from E. nematocypha for the first time.     

Isopimarane diterpenes and flavan derivatives from the twigs of Caesalpinia furfuracea

The first phytochemical investigation of Caesalpinia furfuracea twigs led to the isolation and identification of four new compounds including two isopimarane diterpenes, caesalfurfuric acids A (1) and B (2), and two flavans, (2R)-caesalflavans A (5) and B (6), together with four known compounds, 4-epi-isopimaric acid (3), methyl (E)-3-(3,4-dihydroxyphenyl)acrylate (4), (E)-resveratrol (7) and oxyresveratrol (8). Their structures were elucidated by intensive spectroscopic analysis. Compound 1 was found to exhibit antibacterial activity against MRSA SK1 with an MIC value of 16 μg/mL.     

Phytane and neoclerodane diterpenes from the aerial parts of Inula nervosa Wall.

Three new aliphatic diterpenes (1–3), together with three known neoclerodane-type diterpenes (4–6) were isolated from the aerial parts of Inula nervosa Wall. The structures of 1-3 were elucidated on the basis of 1D and 2D spectroscopic analysis. Additionally, phytane-type and neoclerodane-type diterpenes have not been reported in any species of the genus Inula yet. The phytane-type and neoclerodane-type diterpenes obtained from I. nervosa Wall. suggest this plant maybe have remote genetic relations with other Inula species.     

Synthesis and anti-HIV activity of 2′-deoxy-2′-fluoro-4′-C-ethynyl nucleoside analogs

Based on the favorable antiviral profiles of 4′-substituted nucleosides, novel 1-(2′-deoxy-2′-fluoro-4′-C-ethynyl-β-d-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC₅₀ values of 86 and 1.34 nM, respectively, without significant cytotoxicity. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3 (K101E) and RTMDR. Thus, 2 merits further development as a novel NRTI drug.     

Diterpene content of the alga Dictyota ciliolata from a Moroccan lagoon

Analysis of the secondary metabolites content of the brown alga Dictyota ciliolata, collected from Oualidia lagoon (Morocco), revealed the presence of xenicane and guaiane homologous diterpenes. Two new xenicanes, 1 and 2, co-occurring with the known dictyodial, dictyol C and dictyol H, have been isolated and characterized by spectral methods, mainly by NMR techniques. Compound 2 displayed mild antifungal activity against Candida albicans.     

Chemotaxonomic implications of the absence of sesquiterpene lactones in Grazielia multifida (DC.) R.M.King & H.Rob. (Asteraceae)

The phytochemical investigation of Grazielia multifida aerial parts yielded eight compounds, including four ent-kaurenic acid diterpenes derivatives, 15-tiglinoyloxy-ent-kaur-16-en-19-oic acid (1), 15-hydroxy-ent-kaur-16-en-19-oic acid (2), 17-hydroxy-ent-kaur-15-en-19-oic acid (3) and 15-isovaleroyloxy-ent-kaur-16-en-19-oic acid (4), one amino acid, tryptophan (5), and three flavonoids, eupafolin (6), guaijaverin (7) and quercitrin (8). The structures of the isolated compounds were established based on analysis of their spectroscopic data and comparison with literature. All the compounds were isolated from this species for the first time. The chemotaxonomic significance of the absence of sesquiterpene lactones in G. multifida has also been summarized.     

Bioactive monoterpene indole alkaloids from Nauclea officinalis

Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3–8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1–8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC₅₀ values comparable to that of hydrocortisone. In addition, compounds 1–8 showed significant anti-HIV-1 activities with EC₅₀ ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.     

Pesticidal activity of ingenane diterpenes isolated from Euphorbia kansui against Nilaparvata lugens and Tetranychus urticae

The methanol extract of dried roots of Euphorbia kansui, known as “Gan Sui” in oriental medicine, showed pesticidal activity against brown plant hopper (Nilaparvata lugens Stal) and two-spotted spider mite (Tetranychus urticae Koch). Bioassay-guided fractionation led to the isolation of two active compounds from the dried roots of E. kansui. The substances were identified as 3-O-(2,3-dimethylbutanoyl)-13-O-dodecanoylingenol (1) and 3-O-(2′E,4′Z-decadienoyl)-ingenol (2) by MS and NMR spectral data. Both compounds exhibited insecticidal activity against the brown plant hopper and compound 1 was active against the two-spotted spider mite. Compared to anise oil and eugenol, the two ingenane diterpenes showed greater activity against brown plant hopper. The results suggest that 3-O-(2,3-dimethylbutanoyl)-13-O-dodecanoylingenol and 3-O-(2′E,4′Z-decadienoyl)-ingenol could be used directly as natural pesticides or as lead principles for the control of brown plant hopper and two-spotted spider mite.     

Chemical constituents from Elytropappus rhinocerotis (L.f.) Less.

Phytochemical investigation of the ethyl acetate extract of the aerial parts of Elytropappus rhinocerotis (L.f.) Less. led to the isolation of a coumarin (1), four flavonoids (2–5), and four labdane diterpenes (6–9). The structural characterization of the isolated compounds was based on spectroscopic data. All compounds are reported for the first time from this species and from the genus Elytropappus Cass. The isolation of labdane diterpenes and methoxylated flavones is of taxonomical significance.     

Hit optimization studies of 3-hydroxy-indolin-2-one analogs as potential anti-HIV-1 agents

In the current study, twenty-two compounds based upon 3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one nucleus were designed, synthesized and in vitro evaluated for HIV-1 RT inhibition and anti-HIV-1 activity. Compounds 3d, 5c and 5e demonstrated encouraging potency against RT enzyme as well as HIV-1 in low micromolar to nanomolar concentration with good to excellent safety index. Structure activity relationship studies revealed that halogens such as bromo or chloro at 5th the position of oxindole ring remarkably enhanced the potency against RT. Moreover, methoxy or chloro groups at the ortho position of phenyl ring also significantly favored RT inhibition activity. Seven compounds (3b, 3c, 3d, 3e, 5b, 5c and 5e) with better anti-HIV-1 potency were tested against the mutant HIV-1_K103N strain_. The putative binding mode, as well as interaction patterns of the best active compound 5c with wild HIV-1 RT were studied via docking studies.     

Quinic acid derivatives and coumarin glycoside from the roots and stems of Erycibe obtusifolia

A new quinic acid derivative (1) and a new coumarin glycoside (8), together with six known compounds (2–7) were isolated from the roots and stems of Erycibe obtusifolia. The structures of the new compounds were elucidated by spectroscopic and chemical analyses. The in vitro antiviral activity against the respiratory syncytial virus (RSV) of seven quinic acid derivatives was evaluated by cytopathic effect (CPE) reduction assay. Among them, the dicaffeoylquinic acids (6 and 7) displayed potent in vitro anti-RSV activity.     

Acylated hydroxycinnamic acid glucosides from flowers of Telekia Speciosa

One new derivative of ferulic acid (1), two new caffeic acid derivatives (2 and 3) and three known derivatives of caffeic acid: 6-O-(E)-caffeoyl-glucopyranose (4), (E)-caffeic acid 4-O-β-glucopyranoside (5) and 5-caffeoylquinic acid (chlorogenic acid, 6) were isolated from a butanolic fraction of extract from Telekia speciosa flowers. Moreover, the flavonol glucoside–patulitrin (7) was identified in the analyzed extract. Structures of (E)-ferulic acid 4-O-β-(6-O-2-hydroxyisovaleryl)-glucopyranoside (1), (E)-caffeic acid 4-O-β-(6-O-2-hydroxyisovaleryl)-glucopyranoside (2) and (E)-caffeic acid 4-O-β-(6-O-3-hydroxy-2-methylpropanoyl)-glucopyranoside (3) were elucidated by 1D and 2D NMR, HRESIMS and other spectral analyses.     

Two new cryptoporic acid derivatives from the fruiting bodies of Cryptoporus volvatus

Two new cryptoporic acid derivatives, cryptoporic acid R (1) and 6′,6‴-cryptoporic acid G dimethyl ester (2), together with two known compounds, cryptoporic acid E (3) and cryptoporic acid E pentamethyl ester (4), were isolated from a 90% alcohol extract of the fruiting bodies of Cryptoporus volvatus. Their structures were established on the basis of NMR spectroscopic and mass spectrometry data. Cryptoporic acid E (3) and cryptoporic acid E pentamethyl ester (4) exhibited antiviral activity against porcine reproductive and respiratory syndrome virus.