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.

A comprehensive review of genomics, transcriptomics, proteomics, and metabolomic insights into the differentiation of Pseudomonas aeruginosa from the planktonic to biofilm state: A multi-omics approach.

Biofilm formation by Pseudomonas aeruginosa is primarily responsible for chronic wound and lung infections in humans. These infections are persistent owing to the biofilm's high tolerance to antimicrobials and constantly changing environmental factors. Understanding the mechanism governing biofilm formation can help to develop therapeutics explicitly directed against the molecular markers responsible for this process. After numerous years of research, many genes responsible for both in vitro and in vivo biofilm development remain unidentified. However, there is no "all in one" complete in vivo or in vitro biofilm model. Recent findings imply that the shift from planktonic bacteria to biofilms is a complicated and interrelated differentiation process. Research on the applications of omics technologies in P. aeruginosa biofilm development is ongoing, and these approaches hold great promise for expanding our knowledge of the mechanisms of biofilm formation. This review discusses the different factors that affect biofilm formation and compares P. aeruginosa biofilm formation using the omics approaches targeting essential biological macromolecules, such as DNA, RNA, Protein, and metabolome. Furthermore, we have outlined the application of currently available omics tools, such as genomics, proteomics, metabolomics, transcriptomics, and integrated multi-omics methodologies, to understand the differential gene expression (biofilm vs. planktonic bacteria) of P. aeruginosa biofilms.

Multifunctional apple seed protein hydrolysates: Impact of enzymolysis on the biochemical, techno-functional and in vitro α-glucosidase, pancreatic lipase and angiotensin-converting enzyme inhibition activities.

The work was designed to assess the amelioration effect of papain hydrolysis on the biochemical, techno-functional, and biological properties of apple seed protein isolate (API) after 0-90 min of hydrolysis. Hydrolysis significantly enhanced the nutritional value (protein content ˃ 90 %) while decreasing the average particle size. With increasing hydrolysis time, FTIR analysis revealed a transition from α-helix to ß-turn structure, indicating the unfolding of protein structure. This structural alteration positively influenced the functional characteristics, with samples hydrolyzed for 90 min exhibiting excellent solubility, higher water and oil absorption capacity, foaming capacity, and increased emulsifying activity index. Moreover, samples hydrolyzed for 90 min displayed the highest α-glucosidase (29.62-57.43 %), pancreatic lipase inhibition (12.87-31.08 %), and ACE inhibition (25.32-62.70 %) activity. Interestingly, the inhibiting ability of protein hydrolysates against α-glucosidase and ACE was more effective than pancreatic lipase, suggesting their usefulness as a functional ingredient, particularly in type II diabetes and hypertension management.

Design, Synthesis, Molecular Docking, and In Vitro Antibacterial Evaluation of Benzotriazole-Based ß-Amino Alcohols and Their Corresponding 1,3-Oxazolidines.

In the present study, a series of benzotriazole-based ß-amino alcohols were efficiently synthesized in excellent yields via aminolysis of benzotriazolated epoxides under catalyst- and solvent-free conditions. Further these ß-amino alcohols were successfully utilized to synthesize the corresponding benzotriazole-based oxazolidine heterocyclic derivatives. All the synthesized compounds were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectroscopy for structure elucidation. The compounds were subjected to a microtiter plate-based antimicrobial assay. The antimicrobial activity results reveal that the compounds 4a, 4e, and 5f were found to be active against Staphylococcus aureus (ATCC-25923) with minimum inhibitory concentrations (MICs) of 32, 8, and 64 µM, respectively. Also, the compounds 4a, 4e, 4k, 4i, 4m, 4n, 4o, 5d, 5e, 5f, 5g, and 5h showed effective activity against Bacillus subtilis (ATCC 6633) with MICs of 64, 16, 16, 16, 64, 16, 64, 64, 32, 64, 8, and 16 µM, respectively. A biological investigation was conducted, including molecular docking of two compounds with several receptors to identify and confirm the best ligand-protein interactions. Hence, this study found a significant strategy to diversify the chemical molecules. The synthesized compounds play a potential role as an antibacterial intensifier against some pathogenic bacteria for the development of antibacterial substances.

Antimicrobial, antibiofilm, docking, DFT and molecular dynamics studies on click-derived isatin-thiosemicarbazone-1,2,3-triazoles.

In an effort to develop new antimicrobial and antibiofilm agents, we have designed and synthesized a novel class of isatin-thiosemicarbazone-1,2,3-triazoles through the CuAAC approach. All the synthesized hybrids were characterized by several spectral techniques such as FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS. All the derivatives were evaluated for their antimicrobial and antibiofilm efficacy towards various microbial species. Triazole hybrid 8d exhibited the highest efficacy towards E. coli (MIC = 0.0067 µmol/mL) and S. aureus (MIC = 0.0067 µmol/mL), whereas, compounds 8b, 8c, 8d, 8e, 9a and terminal alkyne (10) significantly inhibited biofilm formation against S. aureus, B. subtilis and E. coli. To find out the structure-activity relationship and binding interactions of synthesized hybrids with enzymes 1KZN and 5TZ1, molecular docking for all the synthesized hybrids was carried out. DFT calculations for all hybrids and the molecular dynamics studies for compounds 9e and 9f were also performed to support the biological behavior of these hybrids.Communicated by Ramaswamy H. Sarma.

Fabrication, characterization, and interventions of protein, polysaccharide and lipid-based nanoemulsions in food and nutraceutical delivery applications: A review.

The fabrication and application of nanoemulsions for incorporating and delivering diverse bioactive compounds, particularly hydrophobic substances, is becoming an increasing focus of research with the potential to improve the nutritional and health status of individuals. Constant advancements in nanotechnological approaches aid in the creation of nanoemulsions using diverse biopolymers such as proteins, peptides, polysaccharides, and lipids to improve the stability, bioactivity, and bioavailability of active hydrophilic and lipophilic compounds. This article provides a comprehensive overview of various techniques used to create and characterize nanoemulsions as well as theories for understanding their stability. The article also highlights the advancement of nanoemulsions in boosting the bioaccessibility of nutraceuticals to help advance their potential use in various food and pharmaceutical formulations.

Correction to "LC-PDA-MS/MS-Based Dereplication Guided Isolation of a New Optical Isomer of 19,20-Epoxycytochalasin-N and Its Cytotoxic Activity".

[This corrects the article DOI: 10.1021/acsomega.2c03037.].

Synthesis, antimicrobial, antibiofilm and computational studies of isatin-semicarbazone tethered 1,2,3-triazoles.

In present era, heterocyclic compounds containing two or three nitrogen atoms play a vital role in drug discovery. In this context, a new class of isatin-semicarbazone tethered 1,2,3-triazole hybrids was synthesized via Cu(I)-mediated azide alkyne cycloaddition reaction. Structural characteristics of the newly derived compounds were identified by various spectral techniques like FTIR, 1H NMR, 13C NMR, HRMS and single crystal X-ray crystallography. Synthesized derivatives were also screened for in vitro antimicrobial and antibiofilm activity against different microbial species. Triazole hybrid 7e showed significant efficacy towards E. coli having MIC of 0.0063 µmol/mL, whereas 6a, 6b, 7a, 7c, 7e, and 7f showed highest percentage of biofilm inhibition against P. aeruginosa. Bioassay results suggested that these triazole hybrids could act as biomaterial for antimicrobial and antibiofilm applications and may constitute a new promising class of antimicrobial and antibiofilm agents. These results were further supported by in silico docking, DFT calculations and ADME studies.

Elucidation of Structural, Morphological, Electrical Parameters, and Anti-Bacterial Activity of Polyaniline-Nanocomposite: New Paradigm of Controlling Bacterial Activity.

In this communication, we purpose an alternative electrical method to determine the anti-bacterial activity of compounds. Polyaniline/magnetite (Fe3O4/PANI) and polyaniline/hydrochloric acid (HCl/PANI) nanocomposites have been prepared. We have tested the anti-bacterial activity of Fe3O4/PANI and HCl/PANI nanocomposites by Agarwell Diffusion Assay and Bacterial Inhibition Assay method. The electrical characteristics of the prepared composites have been measured. The doping of 12% of Fe3O4 in PANI caused a substantial increase in anti-bacterial activity. The observed bacterial inhibition is in agreement with optimized values of resistivity, loss factor, quality factor, and spontaneous magnetization. Sample 2 associated with 12% Fe3O4-PANI composites has a high resistivity of 1.70×106Ω .m among all prepared composites. The magnetic character and insulating nature of Fe3O4 influenced the investigated parameters. The morphological variation of prepared composites is also consistent with electrical parameters. The alleviated energy zone formed by the magnetic behavior of Fe3O4 and interfacial polarization of PANI mitigates the polarization/field of charge carriers of bacteria. These effects altogether diminish the energy of bacterial zone revealed in the experiment. The tuning of electrical parameters provides an alternative to control bacterial growth in various compounds. The proposed method of electrical characterization for the detection of the anti-bacterial activity of the compounds can be very useful in terms of time and cost in contrast to the lab tests performed in biological labs. After implementing an electrical parameter standard equivalent to anti-bacterial activity, real-time detection can be performed by electrical parameters in the fields outside without any hassle, which otherwise is not possible for biological labs.

Biological Activity of Picrorhiza kurroa: A Source of Potential Antimicrobial Compounds against Yersinia enterocolitica.

Yersiniosis, caused by Yersinia enterocolitica, is the third most rampant zoonotic disease in Europe; the pathogen shows high antibiotic resistance. Herbs have multiple anti-microbial components that reduce microorganism resistance. Therefore, an extract of Picrorhiza kurroa (P. kurroa) was evaluated for potential antimicrobial activity. We report that the ethanolic extract of P. kurroa showed effective antimicrobial activity (zone of inhibition: 29.8 mm, Minimum inhibitory concentration (MIC): 2.45 mg/mL, minimum bactericidal concentration (MBC): 2.4 mg/mL) against Yersinia enterocolitica. Potential bioactive compounds from P. kurroa were identified using LC-MS, namely, cerberidol, annonidine A, benzyl formate, picroside-1, and furcatoside A. P. kurroa showed effective antimicrobial potential in skim milk at different pH, acidity, and water activity levels. P. kurroa affected the physiology of Yersinia enterocolitica and reduced the number of live cells. Yersinia enterocolitica, when incubated with P. kurroa extract, showed lower toxin production. Picroside-1 was isolated and showed higher antimicrobial potential in comparison to the standard antibiotic. Picroside-1 lysed the Yersinia enterocolitica cells, as observed under scanning electron microscopy. Docking revealed that picroside-1 (ligand) showed both hydrophilic and hydrophobic interactions with the dihydrofolate reductase (DHFR) protein of Yersinia enterocolitica and that DHFR is a possible drug target. The high activity and natural origin of Picroside-1 justify its potential as a possible drug candidate for Yersinia enterocolitica.

LC-PDA-MS/MS-Based Dereplication Guided Isolation of a New Optical Isomer of 19,20-Epoxycytochalasin-N and Its Cytotoxic Activity.

The Rosellinia sanctae-cruciana extract was subjected to detailed liquid chromatography tandem mass spectrometry studies. A total of 38 peaks were annotated to m/z 508.26, m/z 510.28, m/z 524.26, m/z 526.28, m/z 540.26, m/z 542.27, and m/z 584.28 [M + H]+. The accurate mass, mutually supported UV/vis spectra, and database search identified these compounds as cytochalasins. Systematic dereplication helped identify a peak at m/z 540.26 [M + H]+ as the new compound. Further, the identified compound was purified by high-performance liquid chromatography and characterized by 2D NMR to be 19,20-epoxycytochalasin N1, a new optical isomer of 19,20-epoxycytochalasin-N. It exhibited substantial cytotoxicity with IC50 values ranging from 1.34 to 19.02 µM. This study shows a fast approach for dereplicating and identifying novel cytochalasin metabolites in crude extracts.

Chemical mutagenesis and high throughput media optimization in Tolypocladium inflatum MTCC-3538 leads to enhanced production of cyclosporine A.

Diethyl sulphate-based mutagenesis was performed on fungal strain Tolypocladium inflatum MTCC-3538. Two mutant morphotypes MT1-3538 and MT2-3538 were selected for further chemo-profiling studies. LCMS/MS profiling of fungal crude extract confirmed that the wild-type and mutant strains (MT1-3538, MT2-3538) were competent to produce cyclosporine A. MT2-3538 produced 2.1 fold higher cyclosporine A in comparison to the wild type. Further, LCMS-based high throughput media optimization was performed for MT2-3538 in 20 different media combinations to increase cyclosporine A yield. On the basis of ion-intensity profiling, media combination consisting of Glucose 0.1 g/L; Peptone 0.005 g/L and Valine 0.005 g/L was selected and used for up-scaling purpose. Mutant MT2-3538 with optimized media combination increased cyclosporine yield 16 fold and could potentially be exploited for commercial outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03219-x.

Mutation, Chemoprofiling, Dereplication, and Isolation of Natural Products from Penicillium oxalicum.

Diethyl sulfate (DES)-based chemical mutagenesis was applied on different fungal strains with the aim of diversifying the secondary metabolites. The mutant strain (VRE-MT1) of Penicillium oxalicum was subjected to dereplication (LCMS-based) and isolation of natural products, resulting in obtaining 10 molecules of bioactive potential. Metabolites, viz. tuckolide, methylpenicinoline, 2-acetyl-3,5-dihydroxy-4,6-dimethylbenzeneacetic acid, penicillixanthone A, brefeldin A 7-ketone, and antibiotic FD 549, were observed for the first time from P. oxalicum. The results of antimicrobial activity reveal that the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A have potent antibacterial activity against Bacillus subtilis (ATCC 6633) with minimum inhibitory concentration (MIC) values of 16, 64, and 16 µM, respectively, and the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A were found active against Escherichia coli (ATCC 25922), with MIC values of 16, 64, and 16 µM, respectively. Also, the metabolites N-[2-(4-hydroxyphenyl)ethenyl]formamide and tuckolide showed effective antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid scavenging assays. The mutant VRE-MT1 was found to have 8.34 times higher quantity of N-[2-(4-hydroxyphenyl)ethenyl]formamide as compared to the mother strain. The DES-based mutagenesis strategy has been found to be a potent tool to diversify the secondary metabolites in fungi.

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.

Expanding the chemical diversity through microorganisms co-culture: Current status and outlook.

Natural products (NPs) are considered as a cornerstone for the generation of bioactive leads in drug discovery programs. However, one of the major limitations of NP drug discovery program is "rediscovery" of known compounds, thereby hindering the rate of drug discovery efficiency. Therefore, in recent years, to overcome these limitations, a great deal of attention has been drawn towards understanding the role of microorganisms' co-culture in inducing novel chemical entities. Such induction could be related to activation of genes which might be silent or expressed at very low levels (below detection limit) in pure-strain cultures under normal laboratory conditions. In this review, chemical diversity of compounds isolated from microbial co-cultures, is discussed. For this purpose, chemodiversity has been represented as a chemical-structure network based on the "Tanimoto Structural Similarity Index". This highlights the huge structural diversity induced by microbial co-culture. In addition, the current trends in microbial co-culture research are highlighted. Finally, the current challenges (1 - induction monitoring, 2 - reproducibility, 3 - growth time effect and 4 - up-scaling for isolation purposes) are discussed. The information in this review will support researchers to design microbial co-culture strategies for future research efforts. In addition, guidelines for co-culture induction reporting are also provided to strengthen future reporting in this NP field.

Preclinical development of gastro-protective botanical candidate from Woodfordia fruticosa (Linn.) Kurz: Chemical standardization, efficacy, pharmacokinetics and safety pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Woodfordia fruticosa is traditionally used in the Ayurvedic system of medicine for the treatment of diarrhoea, poisoning, menstrual disorders, ulcers and fertility. In the present study, we report a standardized extract preparation through modern scientific approach for anti-ulcer activity. MATERIALS AND METHODS: The hydro-alcoholic extract of flowers of W. fruticosa was standardized using four chemical markers. The standardized extract was coded as ICB014. HPLC method was developed for identification and quantification of Gallic Acid, Oenothein-C, Quercetin and Kaempferol. Based on the prior published H+, K+-ATPase activity and Anti-bacterial activity against Helicobacter pylori of ICB014, was evaluated for its in-vivo efficacy in gastric ulcers models in rats followed by regulatory safety studies. RESULTS: The extract demonstrated efficacy at 31.25-62.5 mg/kg in gastric ulcer models. The extract was safe by oral route up to 2000 mg/kg in a single dose and NOAEL of 800 mg/kg in 28 days repeat study. Bioequivalent capsule formulation was prepared. CONCLUSIONS: The extract showed anti-ulcer potential and is ready for clinical evaluation.

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.