Bioprospecting of <Emphasis Type="Italic">Diaporthe terebinthifolii</Emphasis> LGMF907 for antimicrobial compounds

Antibiotic-resistant bacteria have been observed with increasing frequency over the past decades, driving the search for new drugs and stimulating the interest in natural products sources. Endophytic fungi from medicinal plants represent a great source of novel bioactive compounds useful to pharmaceutical and agronomical purposes. Diaporthe terebinthifolii is an endophytic species isolated from Schinus terebinthifolius, a plant used in popular medicine for several health problems. The strain D. terebinthifolii LGMF907 was previously reported by our group to produce secondary metabolites with biological activity against phytopathogens. Based on these data, strain LGMF907 was chosen for bioprospecting against microorganisms of clinical importance and for characterization of major secondary metabolites. In this study, different culture conditions were evaluated and the biological activity of this strain was expanded. The crude extracts demonstrated high antibacterial activity against Escherichia coli, Micrococcus luteus, Saccharomyces cerevisiae, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant S. aureus. The compounds diaporthin and orthosporin were characterized and also showed activity against the clinical microorganisms evaluated. This study discloses the first isolation of diaporthin and orthosporin from D. terebinthifolii, and revealed the potential of this endophytic fungus to produce secondary metabolites with antimicrobial activity.     

Novel chlorinated dibenzofurans isolated from the cellular slime mold,Polysphondylium filamentosum,and their biological activities

Cellular slime molds are expected to have the huge potential for producing secondary metabolites including polyketides, and we have studied the diversity of secondary metabolites of cellular slime molds for their potential utilization as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium filamentosum, we obtained new chlorinated benzofurans Pf-1 (4) and Pf-2 (5) which display multiple biological activities; these include stalk cell differentiation-inducing activity in the well-studied cellular slime mold, Dictyostelium discoideum, and inhibitory activities on cell proliferation in mammalian cells and gene expression in Drosophila melanogaster.     

Screening and characterization of endophytic fungi of Panax ginseng Meyer for biocontrol activity against ginseng pathogens

Forty endophytic fungi isolated from ginseng plants were screened to identify metabolites that had antifungal activity against ginseng microbial pathogens. The metabolites from the fungi were extracted from the liquid culture filtrates using ethyl acetate and then evaluated in vitro for antimicrobial activity against ginseng pathogens (Alternaria panax, Botrytis cinerea, Colletotrichum panacicola, Cylindrocarpon destructans, Rhizoctonia solani, and Phytophthora cactorum). Six of the fungi (Colletotrichum pisi, Fusarium oxysporum, Fusarium solani, Phoma terrestris, unknown 1 and 2) showed effective antimicrobial activity against all or some of the ginseng pathogens, with the extract of P. terrestris showing the strongest antimicrobial activity. The extract also showed inhibitory activity against spore germination of the pathogens. Gas chromatography–mass spectrometry (GC–MS) analysis of P. terrestris extract revealed that forty-one compounds were present in metabolites containing mainly N-amino-3-hydroxy-6-methoxyphthalimide (32% of the total metabolites) and 5H-dibenz [B, F] azepine (7%). Treatment with P. terrestris extract also caused morphological changes and reduced expression of the genes involved in mycelial growth and virulence. Treatment also induced defense-related genes in detached Arabidopsis leaves that were inoculated with the pathogens. These results indicate the antimicrobial potential for use of metabolites extracted from the ginseng endophytic fungi as alternatives to chemicals for biocontrol.     

Discovery of Potent Broad Spectrum Antivirals Derived from Marine Actinobacteria

Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable target for the continued development of broadly active antiviral compounds.     

Effects of Q metabolites and related compounds on mitochondrial succinate and NADH oxidase systems

The effects of Q metabolites (Q acid-I, Q acid-II) and related compounds (dihydro Q acid-I, dehydro Q acid-II, QS-n, and their esters) on mitochondrial succinate and NADH oxidase systems were investigated. The activity restoring succinate oxidation in acetone-treated beef heart mitochondria was found to decrease with descending order of carbon number (n) of the side chain of the Q metabolites; activity was restored with Q acid-I (n = 7) to one-third as much as that with Q-7 and Q-10, but Q acid-II (n = 5) did not restore any activity. Of the related compounds with a carboxyalkyl group (QS-n), QS-16-QS-18 (n = 16–18) were found to be most active, and their activities were also correlated with n. The relationship between the restoration of activity and the partition coefficient was considered. NADH oxidation in pentane-treated beef heart submitochondrial particles could be restored with esters of low molecular weight quinones to the same extent as with Q-10, but not with the metabolites.     

Antioxidant and antibacterial activities of the chlorine pigment sclerotiorin from Penicillium mallochii and its chemotaxonomic significance

Penicillium mallochii was isolated as an endophyte from Himatanthus sp. and inoculated in liquid potato-dextrose culture medium, with adjusted to pH 3.6, and incubated for 10 days at 24 °C. Successive column chromatography of the hexane extract afforded the chlorine pigment sclerotiorin. Its structure was determined by NMR and by comparison with the literature. Sclerotiorin showed moderate antioxidant activity and moderate antibacterial against Bacillus subtilis, Staphylococcus aureus, and Micrococcus luteus. The isolation of sclerotiorin from P. mallochii support the taxonomic classification within the Penicillium genus, demonstrating a closer evolutionary relationship among the Penicillium species. Therefore, we suggest that sclerotiorin and the sclerotiorin group of metabolites may be used as chemotaxonomic markers for proper identification of Penicillium species.     

Enantiomeric trans β-aryl-δ-iodo-γ-lactones derived from 2,5-dimethylbenzaldehyde induce apoptosis in canine lymphoma cell lines by downregulation of anti-apoptotic Bcl-2 family members Bcl-xL and Bcl-2

For many years, studies focused on developing new natural or synthetic compounds with antineoplastic activity have attracted the attention of researchers. An interesting group of such compounds seem to be those with both lactone moiety and an aromatic ring which, in addition to antimicrobial or antiviral activity, also exhibit antitumor properties. The study shows antitumor activity of two enantiomeric trans isomers of 5-(1-iodoethyl)-4-(2′,5′-dimethylphenyl)dihydrofuran-2-one. Our aim was to determine their antitumor activity manifested as an ability to induce apoptosis in selected canine cancer cell lines as well as to evaluate differences in their strength depending on the configuration of their stereogenic centers. The enantiomers (+)-(4R,5S,6R)-1 and (?)-(4S,5R,6S)-2 were found to induce classical caspase-dependent apoptosis through downregulation of the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. Although the mechanism of apoptosis induction was the same for both enantiomers, they differed in their strength, as stronger antineoplastic activity in vitro was exhibited by isomer (+)-(4R,5S,6R)-1.     

Regulation of glutamine synthetase adenylylation and deadenylylation by the enzymatic uridylylation and deuridylylation of the PII regulatory protein

Regulation of glutamine synthetase activity in Escherichia coli is mediated by covalent attachment and detachment of an adenylyl group to each subunit of the enzyme [Kingdon, H. S. et al., Proc. Nat. Acad. Sci., 58, 1703, (1967); Wulff, K. D. et al., Biochem. Biophys. Res. Commun.28, 740, (1967)]. Adenylylation and deadenylylation of the enzyme are both catalyzed by a single adenylyltransferase (ATase) whose activity is modulated by various metabolites and by a regulatory protein, P_II [Shapiro, B. M., Biochemistry; Anderson, W. B. et al., Proc. Nat. Acad. Sci.67, 1761 (1970)].The present study confirms preliminary results [Brown, M. S. et al., Proc. Nat. Acad. Sci.68, 2949 (1971)] showing that: (1) the regulatory protein (P_II) exists in two interconvertible forms, P_IIA and P_IID, which, respectively, stimulate adenylylation and deadenylylation activity of ATase; (2) conversion of P_IIA to P_IID requires the presence of UTP, 2-oxoglutarate, ATP, and either Mg²⁺ or Mn²⁺; (3) this conversion involves covalent attachment of a uridine derivative to P_IIA. It is further established that the covalently bound uridine derivative is UMP which is derived from UTP in a reaction catalyzed by a specific uridylyltransferase (UTase). Removal of the covalently bound UMP from P_IID is catalyzed by a separate enzyme, referred to as the uridylyl-removing enzyme (UR-enzyme). This enzyme has an obligatory requirement for Mn²⁺.Regulation of glutamine synthetase activity in E. coli is thus facilitated by a highly sophisticated cascade system of proteins, consisting of an ATase, the regulatory protein (P_II), UTase, and the UR-enzyme. The activities of these various components is rigorously controlled by various metabolites, including glutamine, 2-oxoglutarate, ATP, P_i, UTP, and the divalent cations, Mn²⁺ and Mg²⁺.     

Bioactive polar natural compounds from garlic and onions

Bioactive natural compounds from garlic and onions have been the focus of researches for decades, firstly due to their pharmacological effects, and secondly due to their defence properties against plant diseases. In fact, garlic and onion, belonging to Allium genus, are among the oldest food plants known since ancient times and used as ingredient of many recipes and for therapeutic properties. These plants are well known to produce bioactive apolar sulphur compounds but less is known about their polar natural compounds, such as phenols, sapogenins and saponins, that are more stable to cooking, So, we continued our work on the discovery of polar bioactive metabolites from Allium with the isolation of a number of sapogenins and saponins from the wild onion species Allium elburzense, Allium hirtifolium, Allium atroviolaceum, and Allium minutiflorum, and, more recently, from the cultivated white onion, Allium cepa, and garlic, Allium sativum. In particular, the sapogenins and saponins isolated from A. elburzense and A. hirtifolium, named elburzensosides and hirtifoliosides respectively, exhibited significant antispasmodic properties. In addition, the saponins named minutosides isolated from A. minutiflorum showed promising antimicrobial activity. More recently the phytochemical analysis of A. cepa and A. sativum has been undertaken and afforded the characterization of saponins, phenols and N-cynnamic amides which showed significant antifungal activity.     

Zoosporicidal metabolites from an endophytic fungus Cryptosporiopsis sp. of Zanthoxylum leprieurii

Two polyketides, cryptosporiopsin A (1) and hydroxypropan-2′,3′-diol orsellinate (3), and a natural cyclic pentapeptide (4), together with two known compounds were isolated from the culture of Cryptosporiopsis sp., an endophytic fungus from leaves and branches of Zanthoxylum leprieurii (Rutaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic and spectrometric data. Cryptosporiopsin A and the other metabolites exhibited motility inhibitory and lytic activities against zoospores of the grapevine downy mildew pathogen Plasmopara viticola at 10–25 μg/mL. In addition, the isolated compounds displayed potent inhibitory activity against mycelial growth of two other peronosporomycete phytopathogens, Pythium ultimum, Aphanomyces cochlioides and a basidiomycetous fungus Rhizoctonia solani. Weak cytotoxic activity on brine shrimp larvae was observed.     

Antioxidant,Fusarium growth inhibition and Nasutitermes corniger repellent activities of secondary metabolites from Myracrodruon urundeuva heartwood

Myracrodruon urundeuva heartwood is resistant to biodeterioration and lectin purified from heartwood showed antifungal and termiticidal activities. This report deals with antioxidant, antifungal and termite repellent activities of secondary metabolites from M. urundeuva heartwood. Saline (SE, active hemagglutinin preparation) and methanolic (ME, without hemagglutinating activity) extracts contain phenolic compounds, gallic acid, flavonoids, luteolin, cinamic derivatives, proanthocyanidins, hydrolysable tannins, and leucoanthocyanidins. Both SE and ME showed antioxidant activity and were effective in Fusarium growth inhibition. SE was efficient against Fusarium decemcellulare, Fusarium moniliforme, Fusarium oxysporum, and Fusarium solani but it had little effect against Fusarium lateritium. ME practically had no effect on F. decemcellulare and was more active than SE against F. lateritium. SE induced mortality of Nasutitermes corniger (LC₅₀ of 1.81 mg ml^?1 for soldiers and 2.59 mg ml^?1 for workers) and had no repellent activity. ME had no termiticidal activity but was a good repellent. The detected bioactivities point out the possibility of participation of secondary metabolites in the resistance of M. urundeuva heartwood to biodeterioration. Additionally, the results indicate the use of wood residues, as extracts, a source of natural bioactive agents.     

Isolation and identification of antimicrobial secondary metabolites from Bacillus cereus associated with a rhabditid entomopathogenic nematode

The cell-free culture filtrate of Bacillus cereus associated with an entomopathogenic nematode, Rhabditis (Oscheius) sp., exhibited strong antimicrobial activity. The ethyl acetate extract of the bacterial culture filtrate was purified by silica gel column chromatography to obtain six bioactive compounds. The structure and absolute stereochemistry of these compounds were determined based on extensive spectroscopic analyses (LCMS, FABMS, ¹H NMR, ¹³C NMR, ¹H ?¹H COSY, ¹H ?¹³C HMBC) and Marfey’s method. The compounds were identified as cyclo(D-Pro-D-Leu), cyclo(L-Pro-D-Met), cyclo (L-Pro-D-Phe), cyclo (L-Pro-L-Val), 3,5-dihydroxy-4-ethyl-trans-stilbene, and 3,5-dihydroxy-4-isopropylstilbene, respectively. Compounds recorded antibacterial activity against all four tested bacteria strains of Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. 3,5-dihydroxy-4-isopropylstilbene recorded activity only against Gram-positive bacteria while cyclo(L-Pro-L-Val) recorded no antibacterial activity. Best antibacterial activity was recorded by 3,5-dihydroxy-4-ethyl-trans-stilbene (4 μg/ml) against Escherichia coli. The six compounds recorded significant antifungal activities against five fungal strains tested (Aspergillus flavus, Candida albicans, Fusarium oxysporum, Rhizoctonia solani and Penicillium expansum) and they were more effective than bavistin, the standard fungicide. The activity of cyclo(D-Pro-D-Leu), cyclo(L-Pro-D-Met), 3,5-dihydroxy-4-ethyl-trans-stilbene, and 3,5-dihydroxy-4-isopropylstilbene against Candida albicans was better than amphotericin B. To the best of our knowledge, this is the first report of antifungal activity of the bioactive compounds against the plant pathogenic fungi Fusarium oxysporum, Rhizoctonia solani, and Penicillium expansum. We conclude that the Bacillus cereus strain associated with entomopathogenic nematode is a promising source of natural bioactive secondary metabolites which may receive great benefit as potential sources of new drugs in the agricultural and pharmacological industry.     

Anchoring a Plant Cytochrome P450 via PsaM to the Thylakoids in Synechococcus sp. PCC 7002: Evidence for Light-Driven Biosynthesis

Plants produce an immense variety of specialized metabolites, many of which are of high value as their bioactive properties make them useful as for instance pharmaceuticals. The compounds are often produced at low levels in the plant, and due to their complex structures, chemical synthesis may not be feasible. Here, we take advantage of the reducing equivalents generated in photosynthesis in developing an approach for producing plant bioactive natural compounds in a photosynthetic microorganism by functionally coupling a biosynthetic enzyme to photosystem I. This enables driving of the enzymatic reactions with electrons extracted from the photosynthetic electron transport chain. As a proof of concept, we have genetically fused the soluble catalytic domain of the cytochrome P450 CYP79A1, originating from the endoplasmic reticulum membranes of Sorghum bicolor, to a photosystem I subunit in the cyanobacterium Synechococcus sp. PCC 7002, thereby targeting it to the thylakoids. The engineered enzyme showed light-driven activity both in vivo and in vitro, demonstrating the possibility to achieve light-driven biosynthesis of high-value plant specialized metabolites in cyanobacteria.     

Tetrodecamycin: An unusual and interesting tetronate antibiotic

The tetrodecamycins are a group of secondary metabolites that are characterized by the presence of a tetronate ring in their structure. Originally discovered for their antibiotic activity against Photobacterium damselae ssp. piscicida, the causative agent of pseudotuberculosis in fish, this family of molecules has also been shown to have potent antibiotic activity against methicillin-resistant Staphylococcus aureus. Due to their small size and highly cyclized nature, they represent an unusual member of the much larger group of bioactive molecules called the tetronates. Herein, we review what is known about the mechanism of action of these molecules and also present a hypothesis for their biosynthesis. A deeper understanding of the tetrodecamycins will provide a more holistic view of the tetronate-family, provide new chemical probes of bacterial biology, and may provide therapeutic lead molecules.     

Evaluation of single and joint effect of metabolites isolated from marine sponges,Fasciospongia cavernosa and Axinella donnani on antimicrobial properties

The biochemical mechanisms that marine sponges have developed as a chemical defense to protect themselves against micro and subsequent macrobiofouling process might comprise a potential alternative for the preventing attack of biofilm forming bacteria. The present study investigated the antimicrobial activity of a series of major secondary metabolites isolated from the sponges Fasciospongia cavernosa and Axinella donnani against fouling bacteria. Secomanoalide (1), dehydromanoalide (2) and cavernosine (3) have been isolated from F. cavernosa. Their structures were determined by MS, ¹H NMR spectra analyses and by comparison with those reported in the literature. The most promising activity was exhibited by the metabolites from A. donnani, that is, cerebroside (5) against three strains Aeromonas hydrophila subsp. salmonicida A449 and Erythrobacter litoralis. Our investigation revealed that combined metabolites 1, 2 and 3 retained strong activity but individual metabolite had moderate activity indicating that activity probably results from synergistic interactions between multiple compounds. The antibacterial screening of compounds 3, 5 and synergistic effect of 1–3 against fouling bacteria has been studied for the first time. Further, isolation of manoalide related compounds and their synergistic screening can be accelerated for the development of new biofilm inhibitors.     

Plant secondary metabolite-induced shifts in bacterial community structure and degradative ability in contaminated soil

The aim of the study was to investigate how selected natural compounds (naringin, caffeic acid, and limonene) induce shifts in both bacterial community structure and degradative activity in long-term polychlorinated biphenyl (PCB)-contaminated soil and how these changes correlate with changes in chlorobiphenyl degradation capacity. In order to address this issue, we have integrated analytical methods of determining PCB degradation with pyrosequencing of 16S rRNA gene tag-encoded amplicons and DNA-stable isotope probing (SIP). Our model system was set in laboratory microcosms with PCB-contaminated soil, which was enriched for 8 weeks with the suspensions of flavonoid naringin, terpene limonene, and phenolic caffeic acid. Our results show that application of selected plant secondary metabolites resulted in bacterial community structure far different from the control one (no natural compound amendment). The community in soil treated with caffeic acid is almost solely represented by Proteobacteria, Acidobacteria, and Verrucomicrobia (together over 99 %). Treatment with naringin resulted in an enrichment of Firmicutes to the exclusion of Acidobacteria and Verrucomicrobia. SIP was applied in order to identify populations actively participating in 4-chlorobiphenyl catabolism. We observed that naringin and limonene in soil foster mainly populations of Hydrogenophaga spp., caffeic acid Burkholderia spp. and Pseudoxanthomonas spp. None of these populations were detected among 4-chlorobiphenyl utilizers in non-amended soil. Similarly, the degradation of individual PCB congeners was influenced by the addition of different plant compounds. Residual content of PCBs was lowest after treating the soil with naringin. Addition of caffeic acid resulted in comparable decrease of total PCBs with non-amended soil; however, higher substituted congeners were more degraded after caffeic acid treatment compared to all other treatments. Finally, it appears that plant secondary metabolites have a strong effect on the bacterial community structure, activity, and associated degradative ability.     

Antifungal Activity of Isothiocyanates and Related Compounds: I. Naturally Occurring Isothiocyanates and Their Analogues

Data are presented concerning the antifungal activity of 11 natural isothiocyanates and 27 synthetized analogues in Aspergillus niger, Penicillium cyclopium, and Rhizopus oryzae, as well as in 13 additional saprophytic and parasitic fungi. A remarkable antifungal activity was observed in some analogues of benzylisothiocyanate and β-phenylethylisothiocyanate. The latter-mentioned compounds have not been described previously. In the group of benzylisothiocyanates, a correlation, which was inversely proportional, was detected between ed₁₀₀ values for A. niger and R. oryzae and the corresponding molar solubilities of compounds in water. In contradistinction, no relationship was observed between antifungal activity and chemical reactivity of investigated derivatives.     

Exploitation of the Streptomyces coelicolor A3(2) genome sequence for discovery of new natural products and biosynthetic pathways

Streptomyces, and related genera of Actinobacteria, are renowned for their ability to produce antibiotics and other bioactive natural products with a wide range of applications in medicine and agriculture. Streptomyces coelicolor A3(2) is a model organism that has been used for more than five decades to study the genetic and biochemical basis for the production of bioactive metabolites. In 2002, the complete genome sequence of S. coelicolor was published. This greatly accelerated progress in understanding the biosynthesis of metabolites known or suspected to be produced by S. coelicolor and revealed that streptomycetes have far greater potential to produce bioactive natural products than suggested by classical bioassay-guided isolation studies. In this article, efforts to exploit the S. coelicolor genome sequence for the discovery of novel natural products and biosynthetic pathways are summarized.     

Water-soluble natural products from seaweed have limited potential in controlling bacterial pathogens in fish aquaculture

Seaweeds producing natural products with in vitro efficacy against bacterial pathogens offer the opportunity for therapeutic services in fish aquaculture, for example inhibiting the growth of pathogens through the direct release of bioactive metabolites into the culture environment. The red alga Asparagopsis taxiformis was used to test this hypothesis because of its effective natural products and mechanisms to release these metabolites into the surrounding environment and because it can be cultivated intensively in land-based systems. Here we quantify the release, accumulation and residence time of the major halogenated metabolites from A. taxiformis in the cultivation medium and subsequently test the in vitro bioactivity of these water-soluble metabolites against multiple strains of the pathogenic bacterium Streptococcus iniae. The two major halogenated metabolites in A. taxiformis (bromoform and dibromoacetic acid) were released into the water and reaching steady-state concentrations of 27.7?±?1.5 μg L^?1 and 4.8?±?1.3 μg L^?1, respectively, under standard cultivation conditions. This water delayed the in vitro growth of the pathogenic bacteria S. iniae but did not prevent it. Increasing the levels of A. taxiformis metabolites in the water by three orders of magnitude with aqueous extracts of biomass inhibited the growth of S. iniae, but it was also toxic to fish. In an immersion challenge experiment, intermediate non-ichthyotoxic levels of A. taxiformis metabolites were ineffective as a treatment for barramundi infected by S. iniae. The evidence suggests that there is little potential for A. taxiformis bioactive metabolites to provide therapy services to fish infected with S. iniae.     

Molecular profiling of marine endophytic fungi from green algae: Assessment of antibacterial and anticancer activities

Bioactive natural metabolites, especially from the marine endophytic fungi, are largely unexplored. Endophytic fungi are being increasingly recognized as a group of organisms that produce novel metabolites of industrial importance. This study investigated the anticancer and antibacterial potential of the marine algal endophyte, Penicillium chrysogenum. The different organic solvent extracts of the endophytic fungi grown on different growth medium were analyzed for anticancer and antibacterial activities. The highest inhibitory activity was observed for the ethyl acetate (EA) extract of the culture filtrate grown in potato dextrose broth (PDB) for 21 days, against the tested human breast cancer cell (MCF-7) line. Similarly, the PDB-EA extract showed an appreciable activity against the human pathogens. The biochemical analysis of the Cha EA metabolites revealed terpenoids, steroids, phenolics and flavones. Gas Chromatography (GCMS) data revealed several bioactive compounds such as anthraquinone and cinnamic acid. The Cha EA extract induced membrane damage and thus, apoptosis in MCF-7cells. The secondary metabolites produced by these marine endophytic fungi have contributed to considerable anticancer and antimicrobial activities and hence, this study is an evidence of potential sources of antimicrobial and anticancer compounds from Penicillium chrysogenum.