Computational Methods Reveal a Series of Cyclic and Linear Lichenysins and Surfactins from the Vietnamese Marine Sediment-Derived Streptomyces Strain G222.

The Streptomyces strain G222, isolated from a Vietnamese marine sediment, was confidently identified by 16S rRNA gene sequencing. Its AcOEt crude extract was successfully analyzed using non-targeted LC-MS/MS analysis, and molecular networking, leading to a putative annotation of its chemical diversity thanks to spectral libraries from GNPS and in silico metabolite structure prediction obtained from SIRIUS combined with the bioinformatics tool conCISE (Consensus Annotation Propagation of in silico Elucidations). This dereplication strategy allowed the identification of an interesting cluster of a series of putative cyclic and linear lipopeptides of the lichenysin and surfactin families. Lichenysins (3-7) were isolated from the sub-fraction, which showed significant anti-biofilm activity against Pseudomonas aeruginosa MUC-N1. Their structures were confirmed by detailed 1D and 2D NMR spectroscopy (COSY, HSQC, HMBC, TOCSY, ROESY) recorded in CD3OH, and their absolute configurations were determined using the modified Marfey's method. The isolated lichenysins showed anti-biofilm activity at a minimum concentration of 100 µM. When evaluated for antibacterial activity against a panel of Gram-positive and Gram-negative strains, two isolated lichenysins exhibited selective activity against the MRSA strain without affecting its growth curve and without membranotropic activity. This study highlights the power of the MS/MS spectral similarity strategy using computational methods to obtain a cross-validation of the annotated molecules from the complex metabolic profile of a marine sediment-derived Streptomyces extract. This work provides the first report from a Streptomyces strain of combined cyclic and linear lichenysins and surfactins, known to be characteristic compounds of the genus Bacillus.

Two new flavonoids with antimicrobial activity from the roots of Byttneria aspera Colebr. ex Wall (Malvaceae).

Two new flavonoids, 4',5,7-trihydroxy-5'-methoxy-6,8-dimethylisoflavone (1) and 2',5',7-trihydroxy-5-methoxy-6,8-dimethylflavanone (2) together with the known flavonoids 4´,5,7-trihydroxy-3´-methoxy-6.8-dimethylflavone (3), epigallocatechin (4), 4´-O-methylepicatechin (5) and quercetin (6) were isolated from the roots of Byttneria aspera. The structures of these compounds were determined by means of spectroscopic methods. Compounds 1-6 were submitted to cytotoxic activity assays against three cancer cell lines including KB, MCF7 and A549, as well as their antimicrobial activity against a panel of clinically significant microorganisms. Compound 6 showed moderate cytotoxic activity with IC50 values of 12.7, 56.9 and 17.5 µM against KB, MCF7 and A549. Interestingly, the new compounds 1 and 2 exhibits antimicrobial activity, with compound 1 displaying selective antifungal activity against Candida albicans giving an MIC value of 128 µg/mL, compared to cyclohexamide with 32 µg/mL, while compound 2 shows potent inhibition of the Gram-positive bacterium Enterococcus faecalis displaying an MIC of 64 µg/mL, compared to streptomycin with 256 µg/mL.

A new flavonoid from the leaves of Garcinia mckeaniana Craib and α-glucosidase and acetylcholinesterase inhibitory activities.

From the ethyl acetate extract (EtOAc) of the Vietnamese Garcinia mckeaniana leaves, a new flavone 8-C-glycoside 2'',6''-di-O-acetylvitexin (1), together with six known analogs 2-7 were isolated. Their structures were determined by spectral methods and compared with literature data. In α-glucosidase inhibitory assay, the EtOAc extract and its flavone and biflavone derivatives possessed the significant IC50 range of 9.17-97.53 µM, as compared with that of the positive control acarbose (249 µM). Flavones and biflavones showed are better than flavone glycosides in both α-glucosidase and acetylcholinesterase inhibitory activities[Formula: see text].

Cytotoxic phenolic compounds isolated from the fruits of Macaranga denticulata.

A new modified geranylated flavonoid, 3'-dehydroxy-solophenol C (1), along with 17 known compounds (2-18) were isolated from the fruits of Macaranga denticulata. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR and 2D-NMR. The new geranylated flavonoid 1 showed a moderate cytotoxic activity against the A549 cell line with IC50 value of 16.0 µM. Compound 9 showed the highest cytotoxic activities against KB, HepG2, Lu-1 and MCF7 cell lines with IC50 values of 0.6, 0.8, 1.3 and 1.2 µM, respectively.

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii.

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-ß-D-allopyranosyl-ferulate (3), and methyl-4-ß-D-gulopyranosyl-cinnamate (4), along with six known compounds (5-10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 µM, respectively.

New 9α-Hydroxy-5α,6α-epoxyhydroxysterols from the Vietnamese Marine Sponge Ircinia echinata.

Chemical investigation of the methanol extract of the Vietnamese marine sponge Ircinia echinata led to the isolation of six new 9α-hydroxy-5α,6α-epoxysterols: 5α,6α-epoxycholesta-7,22(E)-dien-3ß,9α-diol (1), 5α,6α-epoxycholesta-7,24(28)-dien-3ß,9α-diol (2), (24R)-5α,6α-epoxy-24-ethyl-cholesta-7-en-3ß,9α-diol (3), 5α,6α-epoxycholesta-7-en-3ß,9α-diol (4), (24S)-5α,6α-epoxyergosta-7,22-dien-3ß,9α-diol (5), and (24R)-5α,6α-epoxy-24-methyl-cholesta-7-en-3ß,9α-diol (6) along with the known 5α-6α-epoxysterols: 5α,6α-epoxystigmasta-7-en-3ß-ol (7), 5α,6α-epoxystigmasta-7,22-dien-3ß-ol (8), and 5α,6α-epoxyergosta-7-en-3ß-ol (9). Their structures and their configurations were established on the basis of high resolution mass spectra and extensive 1D and 2D NMR spectroscopic data and by comparison with the literature. Their cytotoxic activity, evaluated against three human cancer cell lines, MCF-7, Hep-G2 and LU-1, revealed that only compounds 3 and 4 exhibited significant antiproliferative activity and compound 3 showed a selective inhibition towards the MCF-7 human breast cancer cells.

Cytotoxic dammarane-type triterpenoids from the leaves of Viburnum sambucinum.

Four new dammarane-type triterpenoids (1-4) and twelve known compounds (5-16) were isolated from the leaves of Viburnum sambucinum Reinw. ex Blume. Their structures were determined by spectral data analysis, including MS and 2D NMR. Cytotoxic activity evaluation in vitro against four cancer cell lines (KB, LU-1, HepG2 and MCF7) suggested that the octanor-dammarane derivatives were the main cytotoxic components of the leaves of V. sambucinum.

Design, synthesis and cytotoxicity of bengamide analogues and their epimers.

Starting from d-glycero-d-gulo-heptonic acid γ-lactone and amino acids, a number of diastereoisomeric bengamide analogues were synthesized. Optimization of the reaction conditions revealed that microwave irradiation assistance is a powerful method for the preparation of aminolactams, as well as for the coupling reactions of the lactone 5 with aminolactams. Cytotoxic activity evaluation against six cancer cell lines (KB, HepG2, LU1, MCF7, HL60, and Hela) demonstrated that the configuration of C-2' seems to be critical for the cytotoxic activity of compounds 8b (2'R) and 8a (2'S). Additionally, comparison of cytotoxicity of the protected acetonide compounds with that of their corresponding deprotected bengamide analogues suggested that the flexibility of the ketide side chain should be required for their cytotoxic activity.

Two new sesquiterpenes from the fruits of Fissistigma villosissimum.

Two new sesquiterpenes, namely fissistinone (1) and fissistinol (2), along with ten known compounds (3-12), were isolated from the fruits of Fissistigma villosissimum. Their structures were elucidated on the basis of spectral data analysis, including one-dimensional (1D), two-dimensional (2D)-nuclear magnetic resonance (NMR), and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). Compounds 1-8 were evaluated for their cytotoxic activities against KB cell line; however, all these compounds did not show cytotoxic activity.

Synthesis and biological evaluation of febrifugine analogues.

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.