Bioactive Metabolites Produced by Pseudonocardia endophytica VUK-10 from Mangrove Sediments: Isolation, Chemical Structure Determination and Bioactivity.

Chemical investigation of the actinobacterial isolate Pseudonocardia endophytica VUK-10 has led to the segregation of two known bioactive compounds, namely 4-(2-acetamidoethyl) phenyl acetate and 4-((1, 4-dioxooctahydropyrrolo [1, 2-a] pyrazin-3-yl) methyl) phenyl acetate. The strain was isolated from a sediment sample of the Nizampatnam mangrove ecosystem, south coastal Andhra Pradesh, India. The chemical structure of the active compounds was established on the basis of spectroscopic analysis, including (1)H NMR and (13)C NMR spectroscopies, FTIR, and EIMS. The antimicrobial and cytotoxic activities of the bioactive compounds produced by the strain were tested against opportunistic and pathogenic bacteria and fungi and on MDA-MB-231, OAW, HeLa, and MCF-7 cell lines. The compounds exhibited antimicrobial activities against gram-positive and gram-negative bacteria and fungi and also showed potent cytotoxic activity against MDA-MB-231, OAW, HeLa, and MCF-7 cell lines. This is the first example for this class of bioactive compounds isolated from Pseudonocardia of mangrove origin.

Toward synthesis of carbasugars (+)-gabosine C, (+)-COTC, (+)-pericosine B, and (+)-pericosine C.

Asymmetric total synthesis of (+)-gabosine C, (+)-pericosine B, and (+)-pericosine C has been reported from readily available d-(-)-isoascorbic acid and d-ribose involving Grubbs ring closing metathesis, Morita-Baylis-Hillman (MBH) reaction, and Luche reduction.

Semi-synthesis and bio-evaluation of polybrominated diphenyl ethers from the sponge Dysidea herbacea.

The sponge Dysidea herbacea was collected from the Mandapam Coast, Tamilnadu, India. Isolated gram quantities of hydroxylated polybrominated diphenyl ether (HO-PBDE) and semi-synthesized a series of new PBDEs derivatives and tested them for antibacterial and cytotoxic activities.

Stereoselective synthesis of alpinoid-C and its analogues and study of their cytotoxic activity against cancer cell lines.

A simple, highly efficient and stereoselective synthetic route has been developed for synthesis of alpinoid-C (1) and its analogues (2, 3 and 4) from commercially available starting materials by using Wittig olefination, Sharpless asymmetric epoxidation, Grubbs cross metathesis as key steps. All the compounds showed moderate anti-proliferative activity against human leukemia/carcinoma (U-937, THP-1, COLO-205 and HepG2) and mouse melanoma (B16-F10) cancer cell lines. Compounds 3 and 4 are found to be most potent with an IC(50) of 7.53 µM and 32.26 µM on THP-1, 11.12 µM and 7.21 µM on COLO-205 cell lines, respectively.

Synthesis of N-homobicyclic dideoxynucleoside analogues.

Syntheses of six N-homobicyclic dideoxynucleoside analogues are described. The reaction of mannose diacetonide with trimethylsulfoxonium iodide gave a mixture of diastereomeric hydroxymethyl mannose diacetonides in a ratio of 2:5, which was separated by fractional crystallization. The two stereoisomers were converted to bicyclic furanolactols each of which was coupled with three nucleoside bases. Further debenzylations gave the six target N-homobicyclic dideoxynucleosides.

Identification and characterization of stressed degradation products of prulifloxacin using LC-ESI-MS/Q-TOF, MSn experiments: development of a validated specific stability-indicating LC-MS method.

A rapid, specific and novel gradient LC-MS method has been developed and validated for the identification and characterization of stressed degradation products (DPs) of prulifloxacin (PF) using liquid chromatography combined with quadrupole time-of-flight electrospray ionization tandem mass spectrometry (LC/Q-TOF-ESI-MS/MS). PF was subjected to hydrolytic (acidic, alkaline and neutral), oxidation, photolytic and thermal stress, as per ICH guidelines Q1A (R2). The drug showed extensive degradation in hydrolytic and oxidative, while it was stable to thermal and photolytic stress conditions. In total, 13 DPs were formed and the chromatographic separation of drug and its DPs was achieved on a C-18 column (4.6 × 250 mm, 5 µm) using gradient elution method. All the DPs have been identified and characterized using MS(n) experiments and accurate mass measurements. The LC-MS method was validated with respect to specificity, linearity, accuracy, precision and robustness.

Stereoselective first total synthesis, confirmation of the absolute configuration and bioevaluation of botryolide-E.

A simple, first stereoselective total synthesis of botryolide-E has been described. The synthesis started from propylene oxide employing Jacobsen's hydrolytic kinetic resolution (HKR), selective epoxide opening, sharpless asymmetric dihydroxylation, one pot acetonide deprotection and lactonization as key steps. Further, the synthesis confirms the absolute configuration of the natural product botryolide-E and we evaluated the biological behavior of natural product botryolide-E against a panel of bacteria and fungi. Botryolide-E exhibits significant potent activity against Staphylococcus aureus (MTCC 96) (6.25 µg/ml), good against Escherichia coli (MTCC 443) (12.5 µg/ml), Bacillus subtilis (MTCC 441) (25 µg/ml) and compound 1 exhibited good to moderate antifungal activity.

Studies on removal of chromium (VI) from water using chitosan coated Cyperus pangorei.

Environmental contamination by toxic heavy metals is a significant universal problem. The main objective of the study is to use a biodegradable materials like Cyperus pangorei and Chitosan as a composite biosorbent for the removal of Cr(VI) from water. The newly prepared biosorbent is characterized and the capacity of Cr(VI) removal of the biosorbent is carried out systematically by batch mode operations. The adsorption capacity of the biosorbent is examined by changing the parameters like biosorbent dose, varying the initial contact time, varying initial concentration of metal ion and pH of the metal ion solution to know the actual mechanism taking place during the initial sorption process. The experimental data obtained were fitted with the Freundlich, Langmuir and Redlich-Peterson isotherm models and the pseudo first order and the pseudo second order kinetic models. Equilibrium data were fitted very well to the Langmuir Isotherm model and pseudo second order kinetic model. Desorption of the metal ion is also carried out using different concentration of NaOH.

Stereoselective synthesis and biological evaluation of (R)-rugulactone, (6R)-((4R)-hydroxy-6-phenyl-hex-2-enyl)-5,6-dihydro-pyran-2-one and its 4S epimer.

A simple and highly efficient synthetic route has been developed for synthesis of (R)-rugulactone (1a), (6R)-((4R)-hydroxy-6-phenyl-hex-2-enyl)-5,6-dihydro-pyran-2-one (1b) and its 4S epimer 1c by employing proline-catalyzed alpha-aminooxylation, Sharpless epoxidation, Mitsunobu reaction as chirality introuducing steps. The antibacterial and antifungal activity of the compounds 1a, 1b and 1c were evaluated. 1a and 1b showed better antibacterial activity against Pseudomonas aeroginosa (MIC=12.5 microg/ml for 1a, 25 microg/ml for 1b) Klebsiella pneumonia (MIC=25 microg/ml for 1a). Compounds (1a, 1b, 1c) exhibited good to moderate antifungal activity.

Anti inflammatory potential of Decalepis hamiltonii (Wight and Arn) as evidenced by down regulation of pro inflammatory cytokines-TNF-alpha and IL-2.

ETHNOPHARMACOLOGICAL RELEVANCE: Ancient tribes in the Western Ghats of India use the roots of Decalepis hamiltonii Wight and Arn (Asclepiadaceae) for several medicinal purposes particularly inflammation. AIM: To investigate whether the pure compounds obtained from the Decalepis hamiltonii have anti inflammatory activity. MATERIALS AND METHODS: The bioactive lead molecules from the roots of Decalepis hamiltonii were extracted into dichloromethane/methanol and purified by silica gel column chromatography. Structural elucidation of the purified compounds was performed with (1)H and (13)C NMR and mass spectrometry. The in vitro anti inflammatory activity of the pure compounds was studied in mitogen induced peripheral blood mononuclear cells (PBMCs) employing [(3)H] thymidine uptake assay and their effect on cytokine expression by reverse transcriptase polymerase chain reaction (RT-PCR). The inhibition of nuclear factor kappaB (NF-kappaB) activity in the presence of pure compounds was determined in J774 A.1 cells. The cytotoxicity of the compounds was tested using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay kit. RESULTS AND DISCUSSION: Lupeol acetate (Compound 1) and (2S)-5,7,4'-trihydroxy flavanone 4'-O-beta-d-glucoside (Compound 2) isolated from Decalepis hamiltonii roots inhibited the proliferation of mitogen induced PBMCs with an IC(50) value of 8 and 0.5mug/ml respectively. MTT assay revealed the compounds to be non-cytotoxic. Though, both the compounds down regulated the synthesis of mRNA of the pro inflammatory cytokines, interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-alpha), the anti inflammatory cytokine interleukin-10 (IL-10), was found to be up regulated. NF-kappaB activation in J774 A.1 cells were also inhibited by both the compounds. CONCLUSION: Lupeol acetate and (2S)-5,7,4'-trihydroxy flavanone 4'-O-beta-d-glucoside isolated from Decalepis hamiltonii roots showed anti inflammatory activities by down regulating TNF-alpha and IL-2 specific mRNA, besides up regulating the synthesis of mRNA of IL-10.

Isolation, Characterization and Biological evaluation of secondary metabolite from Aspergillus funiculosus.

Screening of Aspergillus funiculosus for bioactive secondary metabolites produced kojic acid, which is know to have wide range of biological properties. It is very active against Gram-negative bacteria, such as Pseudomonas aeruginosa and Escherichia coli, but moderately active against yeasts and Gram-positive bacteria except Staphylococcus epidermidis. Filamentous Fungi are more sensitive to kojic acid. When it exposed to larvicidal activity on Aedes aegypti third instar larvae are more sensitive than early fourth instar larvae.

An unusual novel anti-oxidant dibenzoyl glycoside from Salvinia natans.

An unusual novel and significant anti-oxidant 1,2-dibenzoyl glycoside, natansnin (1), has been isolated from Salvinia natans. The structure of 1 was established by the study of NMR and CD spectral data.

An efficient protocol for alcohol protection under solvent- and catalyst-free conditions.

A simple and highly efficient protocol for pivaloylation of alcohols without using a catalyst under solvent-free conditions has been developed. The key advantages of the reaction are short reaction time, high yields, simple workup, and no need for further purification. Selectivity was observed between primary alcohols vs. secondary alcohols and aliphatic alcohols vs. aromatic alcohols. The accentuated and relevant phenomenon of this method that we observed is in one-pot conversion of TBS protection into Piv protection of the hydroxyl group.

Production of bioactive metabolites by Nocardia levis MK-VL_113.

AIMS: To isolate and identify the bioactive compounds produced by Nocardia levis MK-VL_113. METHODS AND RESULTS: Cultural characteristics of Noc. levis isolated from laterite soils of Guntur region were recorded on International Streptomyces Project media. Morphological studies of the strain through scanning electron microscopy revealed the clear pattern of its hyphal fragmentation into rod-shaped bacilli. Chemical examination of the secondary metabolites of the strain grown on sucrose-tryptone broth led to the isolation of three fractions active against Bacillus cereus. Further analysis of second fraction resulted in the isolation of two active subfractions. Two different phthalate esters, namely, bis-(2-ethylhexyl) phthalate and bis-(5-ethylheptyl) phthalate, were purified from the first active subfraction, and the structural elucidation of these compounds was confirmed on the basis of FT-IR, mass and NMR spectroscopy. The partially purified second subfraction subjected to Gas Chromatography-Mass spectroscopy contained nine components: decanedioic acid; 2,6-piperdione monooxime; 1-eicosanol; beta-1-arabinopyranoside, methyl; cyclopentaneundecanoic acid; hexadecanoic acid; silane, trichloro eicosyl; 1-hexacosanol; and 1,2-dodecanediol. The antimicrobial activity of the bioactive compounds produced by Noc. levis was expressed in terms of minimum inhibitory concentration. CONCLUSIONS: The present study clearly revealed that the metabolites of Noc. levis act as bioactive compounds against gram-positive and gram-negative bacteria, yeast and filamentous fungi. It also supports the idea that there are a number of rare actinomycetes remained to be explored for new bioactive compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: Metabolites of Noc. levis exhibited antibacterial and antifungal activities. This is the first report of bis-(5-ethylheptyl) phthalate as well as the nine partially purified compounds from actinomycetes. In addition, this is also the first report of bis-(2-ethylhexyl) phthalate from the genus Nocardia.

Synthesis of yashabushidiol and its analogues and their cytotoxic activity against cancer cell lines.

A total synthesis of yashabushidiol (1a), a linear diarylheptanoid having 1,3- diol system and its analogues has been achieved by alkynylation of 3-hydroxy-5-phenyl pentanal with substituted phenyl acetylenes. All the compounds have shown significant anti-proliferative activity on human leukemia (THP-1, U-937) and melanoma (A-375) cell lines. Compounds 2a and 2b were found to be most potent with an IC(50) of 12.82 microg/mL and 12.62 microg/mL, respectively, on THP-1 leukemia cell line.

Furano-sesquiterpene from soft coral, Sinularia kavarittiensis: induces apoptosis via the mitochondrial-mediated caspase-dependent pathway in THP-1, leukemia cell line.

Bioassay directed fractionation and purification led to the successful isolation of a furano sesquiterpene, Methyl 5-[(1E,5E)-2,6-Dimethyl octa-1,5,7-trienyl] furan-3-carboxylate (MDTFC), a bioactive component from a soft coral, Sinularia kavarittiensis. Its structure was determined by analyzing (1)H, (13)C NMR and FAB-MS. The results show that MDTFC could efficiently and selectively inhibit the proliferation of several human cancer cell lines. Among all the cell lines, THP-1 was found to be most sensitive (IC(50) 29.59 microM), whereas the peripheral blood mononuclear cells were least effected (IC(50) 464.16 microM). The molecular mechanism of MDTFC mediated apoptosis was investigated for the first time. Induction of apoptosis in THP-1 cells was characterized by cell membrane blebbing, chromatin condensation, DNA fragmentation, and decrease in level of pro-caspases 3, 9 and increase in Bax/Bcl-2 ratio. Our results were further strengthened through cleavage of poly (ADP-ribose) polymerase, reduction of mitochondrial membrane potential (Psim) and cytosolic release of cytochrome c, which are key events during apoptosis. Moreover, phosphatidyl serine exposure and appearance of sub-G1 peak also demonstrated cell death, when analyzed by flow cytometry. DNA fragmentation was prevented moderately when pretreated with caspase-9 inhibitor (Z-LEHD-FMK) and largely with caspase-3 inhibitor (Z-DEVD-FMK). In summary, MDTFC mediated apoptosis involves mitochondria-dependent pathway and the present compound of marine origin might have a therapeutic value against human cancer cell lines and especially on leukemia cells.

Evaluation of antioxidant and antimicrobial properties of Soymida febrifuga leaf extracts.

The present study was designed to evaluate the antioxidant and antimicrobial properties of hexane (LH), methanol (LM) and aqueous (LA) extracts of Soymida febrifuga (Maliaceae) leaves, which is a traditional folk medicine in India. No pharmacological evaluation of this plant (except antiplasmodial activity) has been reported to date. Antioxidant activity of different extracts was evaluated by DPPH free radical scavenging activity, taking total phenolic content (TPC) as an index. Antimicrobial activity was tested against six bacterial and five fungal strains using the agar hole diffusion method and the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) were determined for all the test organisms against the extracts. The results showed that the methanol and aqueous extracts of leaf had a higher antioxidant activity and total phenolic content than the hexane extract. The antioxidant activity and TPC of the extracts were highly correlated. Extracts also showed several degrees of antimicrobial activity against different microbes. The methanol extract was more potent against Aspergillus fumigatus and Candida tropicana. The lowest MIC values obtained for LM, LA and LH were 78, 156, 625 microg/mL against A. fumigatus, C. tropicana and C. albicans, respectively. Hence, this study confirms that Soymida febrifuga leaves possess potent antioxidant and antimicrobial activity.

Antimicrobial activity of Caesalpinia pulcherrima, Euphorbia hirta and Asystasia gangeticum.

The ethanolic extracts of the dry fruits of Caesalpinia pulcherrima, aerial parts of Euphorbia hirta and flowers of Asystasia gangeticum were tested for antimicrobial activity. The three plants exhibited a broad spectrum of antimicrobial activity, particularly against Escherichia coli (enteropathogen), Proteus vulgaris, Pseudomonas aeruginosa and Staphylococcus aureus.

New anticancer bastadin alkaloids from the sponge Dendrilla cactos.

Two new bastadin alkaloids, bastadins-22 (1) and 23 (2), together with six known bastadins, bastadins-6 (3), -12 (4) (formerly basatadin-9), -14 (5), -15 (6), -16 (7), -19 (8), and a common steroid cholesterol were isolated from the sponge Dendrilla cactos. The structures of the isolates were established by the study of extensive spectroscopic analysis (1D and 2D NMR and MS data). Anticancer activity of the isolates has been carried out against Sup-T(1) cancer cells (T cell lymphoma).