Epigenetic modifiers as inducer of bioactive secondary metabolites in fungi.

Scientists are making efforts to search for new metabolites as they are essential lead molecules for the drug discovery, much required due to the evolution of multi drug resistance and new diseases. Moreover, higher production of known drugs is required because of the ever growing population. Microorganisms offer a vast collection of chemically distinct compounds that exhibit various biological functions. They play a crucial role in safeguarding crops, agriculture, and combating several infectious ailments and cancer. Research on fungi have grabbed a lot of attention after the discovery of penicillin, most of the compounds produced by fungi under normal cultivation conditions are discovered and now rarely new compounds are discovered. Treatment of fungi with the epigenetic modifiers has been becoming very popular since the last few years to boost the discovery of new molecules and enhance the production of already known molecules. Epigenetic literally means above genetics that actually does not alter the genome but alter its expression by altering the state of chromatin from heterochromatin to euchromatin. Chromatin in heterochromatin state usually doesn't express because it is closely packed by histones in this state. Epigenetic modifiers loosen the packing of chromatin by inhibiting DNA methylation and histone deacetylation and thus permit the expression of genes that usually remain dormant. This study delves into the possibility of utilizing epigenetic modifying agents to generate pharmacologically significant secondary metabolites from fungi.

Biodiversity and Bioactive Potential of Actinomycetes from Unexplored High Altitude Regions of Kargil, India.

The effectiveness of currently available antimicrobials and anticancer medications is steadily declining due to the emergence of drug resistance. Since actinobacteria are important producers of bioactive substances, we have isolated them from the soil samples of exotic North-Western Himalayan terrains. Out of 128 isolates, 39 strains were prioritized based on their bioactive potential. The diversity analysis revealed higher abundance distribution of actinomycetes in the soil of an open field (68.7%), followed by the mountainside (34.9%), from which most of the bioactive strains were obtained. The extract of the strain S26-11 was found to be highly active against Gram-positive Staphylococcus aureus and Bacillus subtilis with a MIC of 0.5 µg/mL and 1 µg/mL respectively. A cytotoxicity assay (sulforhodamine B) was performed on a series of cancer cell lines (PC-3, MCF-7, A-549, and HCT-116). The extract of the strain S26-11 showed cytotoxic activity against all cancer cell lines with an IC50 of 2 µg/mL against PC-3, 1.9 µg/mL against MCF-7, 0.52 µg/mL against A-549, and 0.83 µg/mL against HCT-116. Moreover, the antioxidant activity was assessed using a DPPH-based assay and the results revealed that the S17-8 isolate showed the highest antioxidant activity with IC50 of 114.136 µg/mL. The Response Surface Methodology (RSM) had helped to optimize the physical parameters for scaling up of the bioactive strain S26-11. The unexplored soil niches of Kargil (UT, Ladakh), India, is rich in actinomycetes which are having potential bioactivities, would be worth to explore for the discovery of bioactive compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01133-1.

Tandem MS-Based Metabolite Profiling of 19,20-Epoxycytochalasin C Reveals the Importance of a Hydroxy Group at the C7 Position for Biological Activity.

Seven cytochalasins, 19,20-epoxycytochalasin N, cytochalasin P1, deacetyl 19,20-epoxycytochalasin C, 19,20-epoxycytochalasin D, 19,20-epoxycytochalasin C, cytochalasin D, and cytochalasin C, were isolated from a fungal (Rosellinia sanctae-cruciana) crude extract. A cytotoxicity assay (sulforhodamine B) was performed on a series of cancer cell lines: HT-29, A-549, PC-3, HCT-116, SW-620, and MCF-7. Simultaneously, the liquid chromatography-mass spectrometry (LC-MS)/MS profile of 19,20-epoxycytochalasin C-treated cell lines revealed that 19,20-epoxycytochalasin C (m/z 524.25) oxidized to a metabolite of m/z 522.25 Da (-2 Da (-2H) from 19,20-epoxycytochalasin C). Further chemical oxidation of 19,20-epoxycytochalasin C using the Dess-Martin reagent produced an identical metabolite. It has been noticed that the parent molecule (19,20-epoxycytochalasin C) showed an IC50 of 650 nM (on HT-29), whereas for the oxidized metabolite (m/z 522.24) of 19,20-epoxycytochalasin C, the IC50 was >10 µM. It is clear that the parent molecule had 16 times higher cytotoxic potential as compared to the oxidized metabolite. The spectroscopic investigation indicated that the oxidation of the hydroxyl (-OH) group occurred at the C7 position in 19,20-epoxycyctochalsin C and led to the inactivation of 19,20-epoxycytochalasin C. Further, cell cycle analysis and histopathological evidence support the findings, and CDK2 could be a possible target of 19,20-epoxycyctochalasin C.

Evaluation of rohitukine-enriched fraction of Dysoxylum binectariferum Hook.f. (leaves) as anti-arthritic phytopharmaceutical candidate: Chemical standardization, in-vivo validation, formulation development and oral pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis is a chronic inflammatory disease of joints. Dysoxylum binectariferum Hook.f (Family: Meliaceae) is a Indian medicinal plant which is traditionally being used to heal inflammation of joints. AIM OF THE STUDY: This work was aimed to carry out chemical standardization, in-vitro/in-vivo validation, oral pharmacokinetics and formulation development of anti-arthritic botanical lead, the rohitukine-enriched fraction of D. binectariferum. MATERIALS AND METHODS: The rohitukine-enriched fraction of D. binectariferum was standardized using four chemical markers and was checked for microbial load, heavy metal content, aflatoxins and pesticides. Its in-vitro inhibitory effect on the lipopolysaccharide (LPS) induced production of pro-inflammatory cytokines TNF-α and IL-6 was studied in THP-1 cells. The in-vivo anti-arthritic activity was investigated in collagen-induced arthritis model in DBA/1J mice. The sustained release capsule formulation was developed and characterized for physicochemical and pharmacokinetic properties. RESULTS: Rohitukine and schumaniofioside A were found to be major chemical constituents of the botanical lead. The rohitukine-enriched fraction of D. binectariferum significantly reduced the production of both pro-inflammatory cytokines TNF-α and IL-6 (>50% inhibition at 3.12 µg/mL) in THP-1 cells. In LPS-treated wild-type mice model, the rohitukine-enriched fraction at 200 mg/kg (PO, QD) completely reduced serum TNF-α levels. In transgenic mice model (collagen-induced arthritis in DBA/1J mice), rohitukine-enriched fraction at 100 mg/kg (PO, QD) dose has resulted in >75% reduction of TNF-α/IL-6 serum levels, 68% reduction in anti-mouse type II collagen IgG1 antibody levels, decreased joint proteoglycan loss and reduced paw edema in DBA/1J mice. The sustained release capsule formulation of rohitukine-enriched fraction showed sustained-release of rohitukine over the period of 24 h, and resulted in an improved plasma-exposure of rohitukine in SD rats. CONCLUSIONS: The data presented herein demonstrated anti-arthritic potential of rohitukine-enriched fraction of D. binectariferum and this study will serve as the benchmark for further research on this botanical lead and developed sustained release capsule formulation.

Bioactive compounds and pharmacological and food applications of Syzygium cumini - a review.

The present review explores the nutritional, phytochemical and pharmacological potential as well as diverse food usages of Syzygium cumini. S. cumini is a traditional medicinal plant with various bioactive compounds distributed in all parts of the plant. The major bioactive compounds present in the edible part are myricetin, oxalic acid, gallic acid, citronellol, cyanidin diglucoside, hotrienol, phytosterols, flavonoids, carotenoids and polyphenols as well as micronutrients, accounting for numerous health benefits. The potential benefits of these bioactive compounds are to prevent/reduce metabolic abnormalities and various diseases. The health protective effects and functional properties of the plant were proved by different in vitro and in vivo pharmacological studies. All parts of the plant have good health benefits like hypoglycemic, anti-inflammatory, antianemic, antibacterial, antioxidant, antiallergic, hepatoprotective, hypolipidemic and antipyretic properties. The fruit of S. cumini can be consumed raw or processed in the form of jam, jellies, wine, fermented beverages and many other value added food products.

Valproic acid induces three novel cytotoxic secondary metabolites in Diaporthe sp., an endophytic fungus from Datura inoxia Mill.

Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identified as xylarolide A (1), diportharine A (2) and xylarolide B (3) along with one known compound xylarolide (4). The structures of all the compounds (1-4) were determined by detailed analysis of 1D and 2D NMR spectroscopic data. The relative configurations of compounds 1-3 were determined with the help of NOESY data and comparison of optical rotations with similar compounds with established stereochemistry. All the isolated compounds were screened for antibacterial, antioxidant and cytotoxic activities. Xylarolide A (1) and xylarolide (4) displayed significant growth inhibition of MIAPaCa-2 with an IC50 of 20 and 32 µM respectively and against PC-3 with an IC50 of 14 and 18 µM respectively. Moreover, compound 1 displayed significant DPPH scavenging activity with EC50 of 10.3 µM using ascorbic acid as a positive control.

Citrus medica: nutritional, phytochemical composition and health benefits - a review.

Citrus medica (Citron) is an underutilized fruit plant having various bioactive components in all parts of the plant. The major bioactive compounds present are iso-limonene, citral, limonene, phenolics, flavonones, vitamin C, pectin, linalool, decanal, and nonanal, accounting for several health benefits. Pectin and heteropolysachharides also play a major role as dietary fibers. The potential impact of citron and its bioactive components to prevent or reverse destructive deregulated processes responsible for certain diseases has attracted different researchers' attention. The fruit has numerous nutraceutical benefits, proven by pharmacological studies; for example, anti-catarrhal, capillary protector, anti-hypertensive, diuretic, antibacterial, antifungal, anthelmintic, antimicrobial, analgesic, strong antioxidant, anticancerous, antidiabetic, estrogenic, antiulcer, cardioprotective, and antihyperglycemic. The present review explores new insights into the benefits of citron in various body parts. Throughout the world, citron has been used in making carbonated drinks, alcoholic beverages, syrup, candied peels, jams, marmalade, cordials, and many other value added products, which suggests it is an appropriate raw material to develop healthy processed food. In the present review, the fruit taxonomical classification, beneficial phytochemicals, antioxidant activities, and health benefits are discussed.

Recent advances in near-infrared light-responsive nanocarriers for cancer therapy.

In recent years, research has focused on the development of smart nanocarriers that can respond to specific stimuli. Among the various stimuli-responsive platforms for cancer therapy, near-infrared (NIR) light (700-1000nm)-responsive nanocarriers have gained considerable interest because of their deeper tissue penetration capacity, precisely controlled drug release, and minimal damage towards normal tissues. In this review, we outline various therapeutic applications of NIR-responsive nanocarriers in drug delivery, photothermal therapy (PTT), photodynamic therapy (PDT), and bioimaging. We also highlight recent trends towards NIR-responsive combinatorial therapy and multistimuli-responsive nanocarriers for improving therapeutic outcomes.

Preparation, characterization and cytotoxic evaluation of bovine serum albumin nanoparticles encapsulating 5-methylmellein: A secondary metabolite isolated from Xylaria psidii.

In this study, 5-methylmellein (5-MM) loaded bovine serum albumin nanoparticles (BSA NPs) were developed using desolvation technique. The developed nanoparticles were characterized for their mean particle size, polydispersity, zeta potential, loading efficiency, X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and release profile. The developed nanoparticles were spherical in shape under transmission electron microscopy (TEM) and atomic force microscopy (AFM). The developed 5-MM loaded BSA NPs demonstrated a mean particle size with a diameter of 154.95 ±â€¯4.44 nm. The results from XRD and DSC studies demonstrated that the crystal state of the 5-MM was converted to an amorphous state in polymeric matrix. The encapsulation and loading efficiency was found to be 73.26 ±â€¯4.48% and 7.09 ±â€¯0.43%. The in vitro cytotoxicity in human prostate cancer cell line (PC-3), human colon cancer cells (HCT-116) and human breast adenocarcinoma cell line (MCF-7) cells demonstrated enhanced cytotoxicity of 5-MM BSA NPs as compared to native 5-MM after 72-h treatment. The enhancement in cytotoxicity of 5-MM BSA NPs was also supported by increase in cellular apoptosis, mitochondrial membrane potential loss and generation of high reactive oxygen species (ROS). In conclusion, these findings collectively indicated that BSA nanoparticles may serve as promising drug delivery system for improving the efficacy of 5-methylmellein.

Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells.

BACKGROUND: Endophytes have proven to be an invaluable resource of chemically diverse secondary metabolites that act as excellent lead compounds for anticancer drug discovery. Here we report the promising cytotoxic effects of Cladosporol A (HPLC purified >98%) isolated from endophytic fungus Cladosporium cladosporioides collected from Datura innoxia. Cladosporol A was subjected to in vitro cytotoxicity assay against NCI60 panel of human cancer cells using MTT assay. We further investigated the molecular mechanism(s) of Cladosporol A induced cell death in human breast (MCF-7) cancer cells. Mechanistically early events of cell death were studied using DAPI, Annexin V-FITC staining assay. Furthermore, immunofluorescence studies were carried to see the involvement of intrinsic pathway leading to mitochondrial dysfunction, cytochrome c release, Bax/Bcl-2 regulation and flowcytometrically measured membrane potential loss of mitochondria in human breast (MCF-7) cancer cells after Cladosporol A treatment. The interplay between apoptosis and autophagy was studied by microtubule dynamics, expression of pro-apoptotic protein p21 and autophagic markers monodansylcadaverine staining and LC3b expression. RESULTS: Among NCI60 human cancer cell line panel Cladosporol A showed least IC50 value against human breast (MCF-7) cancer cells. The early events of apoptosis were characterized by phosphatidylserine exposure. It disrupts microtubule dynamics and also induces expression of pro-apoptotic protein p21. Moreover treatment of Cladosporol A significantly induced MMP loss, release of cytochrome c, Bcl-2 down regulation, Bax upregulation as well as increased monodansylcadaverine (MDC) staining and leads to LC3-I to LC3-II conversion. CONCLUSION: Our experimental data suggests that Cladosporol A depolymerize microtubules, sensitize programmed cell death via ROS mediated autophagic flux leading to mitophagic cell death. The proposed mechanism of Cladosporol A -triggered apoptotic as well as autophagic death of human breast cancer (MCF-7) cells. The figure shows that Cladosporol A induced apoptosis through ROS mediated mitochondrial pathway and increased p21 protein expression in MCF-7 cells in vitro.

Polysaccharides based nanomaterials for targeted anti-cancer drug delivery.

Polysaccharides, an important class of biological polymers, are effectively bioactive, nontoxic, hydrophilic, biodegradable and offer a wide diversity in structure and properties. These can be easily modified chemically and biochemically to enhance the bioadhesion with biological tissues, better stability and can improve bioavailability of drugs. Most of the chemotherapeutic drugs have a narrow therapeutic index, slow drug delivery systems and poor water solubility that usually proves toxic to human bodies. The inherent biocompatibility of these biopolymers have shown enhancement of solubility of some chemotherapeutic drugs which also leads to the preparation of nanomaterials for the delivery of antibiotics, anticancer, proteins, peptides and nucleic acids using several routes of administration. Recently, synthesis and research on polysaccharides based nanomaterials have gained enormous attention as one of the most applicable resources in nanomedicine area. This review article will provide a specific emphasis on polysaccharides as natural biomaterials for targeted anticancer drug delivery system.

Green synthesis and anticancer potential of chalcone linked-1,2,3-triazoles.

A series of chalcone linked-1,2,3-triazoles was synthesized via cellulose supported copper nanoparticle catalyzed click reaction in water. The structures of all the compounds were analyzed by IR, NMR and Mass spectral techniques. All the synthesized products were subjected to 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay against a panel of four human cancer cell lines (MCF-7, MIA-Pa-Ca-2, A549, HepG2) to check their anticancer potential. Compound 6h was found to be most active against all the tested cancer cell lines with IC50 values in the range of 4-11 µM and showed better or comparable activity to the reference drug against all the tested cell lines. Cell cycle analysis revealed that compound 6h induces apoptosis and G2/S arrest in MIA-Pa-Ca-2 cells. Compound 6h triggers mitochondrial potential loss in pancreatic cancer MIA-Pa-Ca-2 cells. Further, Compound 6h also triggers caspase-3 and PARP-1 cleavage, which increases in dose dependent manner.

Isolation and characterization of bioactive metabolites from Xylaria psidii, an endophytic fungus of the medicinal plant Aegle marmelos and their role in mitochondrial dependent apoptosis against pancreatic cancer cells.

BACKGROUND: The genus Xylaria has been reported as a rich source of biologically active secondary metabolites. In the present study, an endophytic fungus Xylaria psidii has been isolated from the leaf sample of Aegle marmelos (L.) Corr., characterized on the basis of its morphological features and sequence data for the ITS region (KU291350) of the nuclear ribosomal DNA. Biological screening of ethyl acetate extract of Xylaria psidii displayed a potential therapeutic effect on pancreatic cancer cells. HYPOTHESIS: This study was designed systematically to explore Xylaria psidii, an endophytic fungus for the identification of biologically active secondary metabolites against pancreatic cancer cells. METHODS: While exploring the bioactive secondary metabolites, a sensitive and reliable LC-MS based dereplication approach was applied to identify four compounds A-D from fungal extract. Further bioactivity guided isolation of fungal extract yielded two major metabolites 1 and 2. The structures of 1 and 2 have been determined by detailed spectroscopic analysis including MS, NMR, IR and UV data and similarity with published data. Xylarione A (1) is new whereas (-) 5-methylmellein (2) is reported for the first time from X. psidii. Both the isolated compounds were screened for their effect on the viability and proliferation against a panel of cancer cell lines (MCF-7, MIA-Pa-Ca-2, NCI-H226, HepG2 and DU145) of different tissue origin. RESULTS: Compounds 1 and 2 exhibited cytotoxicity against pancreatic cancer (MIA-Pa-Ca-2) cells with IC50 values of 16.0 and 19.0 µm, respectively. The cell cycle distribution in MIA-Pa-Ca-2 cells, confirmed a cell cycle arrest at the sub-G1 phase. Cell death induced by 1 and 2 displayed features characteristic of apoptosis. Flow cytometry based analysis of 1 and 2 using Rhodamine-123 displayed substantial loss of mitochondrial membrane potential in a concentration dependent manner by both the compounds. CONCLUSION: Results conclude that the isolated compounds 1 and 2 are responsible for the activity shown by crude ethyl acetate extract and may act as potential leads for medicinal chemists for designing more potent analogs.

Hybrid surfactants decorated with copper ions: aggregation behavior, antimicrobial activity and anti-proliferative effect.

In the present study, the emphasis is laid on the self aggregation behavior of copper based inorganic-organic hybrids in aqueous media. The two complexes, cationic hexadecyl pyridinium trichloro cuprate (1 : 1), [Cp](+)[CuCl3](-), and bishexadecylpyridinium tetrachloro cuprate (2 : 1), [Cp2](2+)[CuCl4](2-), were synthesized using the ligand insertion method. The complexes were characterized using elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and thermogravimetric analysis. The copper complexes were found to be thermally stable, and in the solid state, they possessed the perovskite arrangement with [Cp2](2+)[CuCl4](2-) exhibiting superior stability and crystallinity. The self aggregation behavior of the prepared complexes was analyzed in solution phase (in aqueous medium) using surface tension, conductivity, XRD and small angle neutron scattering (SANS). The results show that the presence of copper as a co-ion in both the stoichiometries results in lower critical micellization concentrations than their precursor. Micellization was thermodynamically spontaneous and micelles formed were ellipsoidal in shape and underwent a prolate ellipsoidal growth with an increase in the concentration of metallosurfactant, as estimated from the SANS. Furthermore, these metallosurfactants were investigated for biocompatibility (using hemolytic assay), antimicrobial activity (fungus and bacteria) and cytotoxicity using human cancerous cells. The hemolysis activity was found to depend on the aggregated state of the metallosurfactants, displaying the highest activity in the monomeric state, and the minimum for post micellar concentrations. The surfactants were found to enhance the antibacterial activity by twofold or more, with the addition of metal in both the stoichiometries. On the contrary, for anticancer and antifungal activities, barely any regular trend or generalization could be obtained. Nevertheless, the copper complexes exhibited high IC50 values for fR2 (healthy cells) signifying their higher safety in comparison to the cancerous cells.

Evaluation of bishexadecyltrimethyl ammonium palladium tetrachloride based dual functional colloidal carrier as an antimicrobial and anticancer agent.

We have developed a dual function carrier using bishexadecyltrimethyl ammonium palladium tetrachloride, which has anticancer as well as antibacterial activity, using a ligand insertion method with a simple and easy work procedure. The complex is prepared by a simple and cost effective method using hexadecyltrimethyl ammonium chloride and palladium chloride under controlled stoichiometry. Herein, we report the aggregation (self assembly) of the metallosurfactant having palladium as a counter ion, in aqueous medium along with its binding affinity with bovine serum albumin. The palladium surfactant has exhibited excellent antimicrobial efficacy against fungus and bacteria (both Gram-positive and Gram-negative bacteria). Cytotoxicity of palladium surfactant against cancerous (Human leukemia HL-60, pancreatic MIA-Pa-Ca-2 and prostate cancer PC-3) and healthy cells (fR2 human breast epithelial cells) was also evaluated using MTT assay. The present dual functional moiety shows a low IC50 value and has potential to be used as an anticancer agent. Our dual function carrier which itself possesses antimicrobial and anticancer activity represents a simple and effective system and can also be utilized as a drug carrier in the future.

Secalonic Acid-D Represses HIF1α/VEGF-Mediated Angiogenesis by Regulating the Akt/mTOR/p70S6K Signaling Cascade.

Tumor angiogenesis is a validated target for therapeutic intervention, but agents that are more disease selective are needed. Here, we report the isolation of secalonic acid-D (SAD), a mycotoxin from a novel source that exhibits potent antiangiogenic antitumor activity. SAD inhibited multiple HIF1α/VEGF-arbitrated angiogenesis dynamics as scored in human umbilical vascular endothelial cells and human MCF-7 breast tumor xenografts. Similarly, SAD suppressed VEGF-induced microvessel sprouting from rat aortic ring and blood vessel formation in the Matrigel plug assay in C57/BL6J mice. Under normoxic or hypoxic conditions, SAD inhibited cell survival through the Akt/mTOR/p70S6K pathway, with attendant effects on key proangiogenesis factors, including HIF1α, VEGFR, and MMP-2/MMP-9. These effects were reversed by cotreatment with the Akt inhibitors perifosine and GSK69069 or by the addition of neutralizing VEGF antibodies. The apoptotic properties of SAD were determined to be both extrinsic and intrinsic in nature, whereas the cell-cycle inhibitory effects were mediated by altering the level of key G1-S transition-phase proteins. In experimental mouse models of breast cancer, SAD dosing produced no apparent toxicities (either orally or intraperitoneal) at levels that yielded antitumor effects. Taken together, our findings offered a preclinical validation and mechanistic definition of the antiangiogenic activity of a novel mycotoxin, with potential application as a cancer-selective therapeutic agent.

Dysoxylum binectariferum bark as a new source of anticancer drug camptothecin: bioactivity-guided isolation and LCMS-based quantification.

Camptothecin (CPT, 1) is a potent anticancer natural product which led to the discovery of two clinically used anticancer drugs topotecan and irinotecan. These two drugs are semisynthetic analogs of CPT, and thus the commercial production of CPT as a raw material from various plant sources and tissue culture methods is highly demanding. In the present study, the Dysoxylum binectariferum bark, was identified as an alternative source of CPT, through bioassay-guided isolation. The barks showed presence of CPT (1) and its 9-methoxy analog 2, whereas CPT alkaloids were not present in seeds and leaves. This is the first report on isolation of CPT alkaloids from Meliaceae family. An efficient chromatography-free protocol for enrichment and isolation of CPT from D. binectariferum has been established, which was able to enrich CPT up to 21% in the crude extract. The LCMS (MRM)-based quantification method revealed the presence of 0.105% of CPT in dry barks of D. binectariferum. The discovery of CPT from D. binectariferum bark will certainly create a global interest in cultivation of this plant as a new crop for commercial production of CPT. Isolation of anticancer drug CPT from this plant, indicates that along with rohitukine, CPT and 9-methoxy CPT also contributes significantly to the cytotoxicity of D. binectariferum.

Capsaicin production by Alternaria alternata, an endophytic fungus from Capsicum annum; LC-ESI-MS/MS analysis.

Alternaria alternata, an endophytic fungus capable of producing capsaicin (1) was isolated from Capsicum annum. The endophyte was found to produce capsaicin upto three generations. Upscaling of the fermentation broth led to the isolation of one known and one compound characterized as 2,4-di-tert-butyl phenol (2) and alternariol-10-methyl ether (3) respectively. Compound 1 and 3 were identified and quantified using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) system through multiple reaction monitoring (MRM). Furthermore, compound 3 displayed a range of cytotoxicity against a panel of human cancer cell lines and was found to induce apoptosis evidenced by Hoechst staining and loss of mitochondrial-membrane potential in HL-60 cells.

Synthesis, antimicrobial and cytotoxicity study of 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines.

A series of new 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines (3 and 7) was synthesized in good yields and the structure was determined with the help of NMR, 2D-NMR, HRMS studies and X-ray crystallography. These compounds were tested in vitro for their antibacterial activity against Gram-positive and Gram-negative bacteria and as well as for antifungal activity. The compounds 3c, 3e, 7a, 7d and 7k showed significant antibacterial activity and 7l showed moderate antifungal activity. The cytotoxicity of 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines showed that 3e and 7e are more effective against breast, lung and colon cell proliferation.