{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:37:11Z","timestamp":1792499831000,"version":"4.5.0"},"reference-count":91,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["129778"],"award-info":[{"award-number":["129778"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["21\/76"],"award-info":[{"award-number":["21\/76"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation (PRF)","doi-asserted-by":"publisher","award":["129778"],"award-info":[{"award-number":["129778"]}],"id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation (PRF)","doi-asserted-by":"publisher","award":["21\/76"],"award-info":[{"award-number":["21\/76"]}],"id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The continuous burden of human immunodeficiency virus-1 in Sub-Saharan Africa, coupled with the inability of antiretroviral agents to eradicate HIV-1 from viral reservoirs, the potential risks of drug resistance development, and the development of adverse effects, emphasizes the need to develop a new class of HIV-1 inhibitors. Here, we cultivated four endophytic fungal isolates from a medicinal plant, Albizia adianthifolia with the addition of small epigenetic modifiers, sodium butyrate, and valproic acid, to induce the expression of biosynthetic gene clusters encoding active secondary metabolites with probable anti-HIV activities. We identified a non-toxic crude extract of the endophytic fungus Penicillium chrysogenum treated with sodium butyrate to possess significantly greater anti-HIV activity than the untreated extracts. Penicillium chrysogenum P03MB2 showed anti-HIV activity with an IC50 of 0.6024 \u00b5g\/mL compared to untreated fungal crude extract (IC50 5.053 \u00b5g\/mL) when treated with sodium butyrate. The profile of secondary metabolite compounds from the bioactive, partially purified extracts were identified by gas chromatography-mass spectrometry (GC-MS), and more bioactive compounds were detected in treated P. chrysogenum P03MB2 fractions than in untreated fractions. Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro (13.64%), cyclotrisiloxane, hexamethyl (8.18%), cyclotetrasiloxane, octamethyl (7.23%), cyclopentasiloxane, decamethyl (6.36%), quinoline, 1,2-dihydro-2,24-trimethyl (5.45%), propanenitrile (4.55%), deca-6,9-diene (4.55%), dibutyl phthalate (4.55%), and silane[1,1-dimethyl-2-propenyl)oxy]dimethyl (2.73%) were the most abundant compounds. These results indicate that treatment of endophytic fungi with small epigenetic modifiers enhances the secretion of secondary metabolites with stronger anti-HIV-1 properties, acknowledging the feasibility of epigenetic modification as an innovative approach for the discovery of cryptic fungal metabolites which can be developed into therapeutic compounds.<\/jats:p>","DOI":"10.3390\/microorganisms11061404","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:10:53Z","timestamp":1685203853000},"page":"1404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Epigenetic Induction of Secondary Metabolites Production in Endophytic Fungi Penicillium chrysogenum and GC-MS Analysis of Crude Metabolites with Anti-HIV-1 Activity"],"prefix":"10.3390","volume":"11","author":[{"given":"John P.","family":"Makhwitine","sequence":"first","affiliation":[{"name":"Discipline of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, College of Health Science, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hezekiel M.","family":"Kumalo","sequence":"additional","affiliation":[{"name":"Drug Research and Innovation Unit, Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2323-282X","authenticated-orcid":false,"given":"Sizwe I.","family":"Ndlovu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-9201","authenticated-orcid":false,"given":"Nompumelelo P.","family":"Mkhwanazi","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.coph.2010.04.011","article-title":"Antiretroviral drugs","volume":"10","year":"2010","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.2105\/AJPH.2009.184796","article-title":"Antiretroviral therapy as HIV prevention: Status and prospects","volume":"100","author":"Mayer","year":"2010","journal-title":"Am. J. Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2009.10.002","article-title":"The development of antiretroviral therapy and its impact on the HIV-1\/AIDS pandemic","volume":"85","author":"Broder","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.3389\/fmicb.2015.01444","article-title":"Natural products as anti-HIV agents and role in HIV-associated neurocognitive disorders (HAND): A brief overview","volume":"6","author":"Kurapati","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/2040206617705500","article-title":"Potential of small-molecule fungal metabolites in antiviral chemotherapy","volume":"25","author":"Roy","year":"2017","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6112","DOI":"10.1016\/j.bmc.2014.08.039","article-title":"Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi","volume":"22","author":"Bashyal","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1021\/np400683h","article-title":"Phenylspirodrimanes with anti-HIV activity from the sponge-derived fungus Stachybotrys chartarum MXH-X73","volume":"76","author":"Ma","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"a006882","DOI":"10.1101\/cshperspect.a006882","article-title":"HIV-1 reverse transcription","volume":"2","author":"Hu","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.2165\/00003495-200565130-00002","article-title":"Emerging drug targets for antiretroviral therapy","volume":"65","author":"Reeves","year":"2005","journal-title":"Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1002\/hlca.200390281","article-title":"Isolation, structure, and HIV-1 integrase inhibitory activity of Xanthoviridicatin E and F, two novel fungal metabolites produced by Penicillium chrysogenum","volume":"86","author":"Singh","year":"2003","journal-title":"Helv. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.coviro.2012.12.002","article-title":"HIV-1 entry inhibitors: Recent development and clinical use","volume":"3","author":"Henrich","year":"2013","journal-title":"Curr. Opin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/COH.0b013e328322402e","article-title":"HIV-1 Entry inhbitors: An overview","volume":"4","author":"Kuritzkes","year":"2009","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/jac\/dkg086","article-title":"HIV protease inhibitors: Antiretroviral agents with anti-inflammatory, anti-angiogenic and anti-tumour activity","volume":"51","author":"Monini","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1056\/NEJM199804303381808","article-title":"HIV-protease inhibitors","volume":"338","author":"Flexner","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.3389\/fmicb.2018.02325","article-title":"Antiviral Agents From Fungi: Diversity, Mechanisms and Potential Applications","volume":"9","author":"Linnakoski","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.fgb.2019.06.001","article-title":"Strategies to establish the link between biosynthetic gene clusters and secondary metabolites","volume":"130","author":"Mortensen","year":"2019","journal-title":"Fungal Genet. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrmicro3496","article-title":"Discovery of microbial natural products by activation of silent biosynthetic gene clusters","volume":"13","author":"Rutledge","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.3390\/md13084754","article-title":"The Sound of Silence: Activating Silent Biosynthetic Gene Clusters in Marine Microorganisms","volume":"13","author":"Reen","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/femsre\/fuw035","article-title":"Antibiotic dialogues: Induction of silent biosynthetic gene clusters by exogenous small molecules","volume":"41","author":"Okada","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"815008","DOI":"10.3389\/fmicb.2022.815008","article-title":"Epigenetic Activation of Silent Biosynthetic Gene Clusters in Endophytic Fungi Using Small Molecular Modifiers","volume":"13","author":"Pillay","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.bbrc.2016.09.041","article-title":"Fusarithioamide A, a new antimicrobial and cytotoxic benzamide derivative from the endophytic fungus Fusarium chlamydosporium","volume":"479","author":"Ibrahim","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13568-017-0343-z","article-title":"Epigenetic modifier induced enhancement of fumiquinazoline C production in Aspergillus fumigatus (GA-L7): An endophytic fungus from Grewia asiatica L.","volume":"7","author":"Magotra","year":"2017","journal-title":"AMB Express"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/B978-0-12-404634-4.00018-8","article-title":"Use and discovery of chemical elicitors that stimulate biosynthetic gene clusters in Streptomyces bacteria","volume":"517","author":"Moore","year":"2012","journal-title":"Methods Enzymol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s10295-013-1309-z","article-title":"Triggers and cues that activate antibiotic production by actinomycetes","volume":"41","author":"Zhu","year":"2014","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.sajb.2020.07.019","article-title":"Epigenetic-based developments in the field of plant endophytic fungi","volume":"134","author":"Gupta","year":"2020","journal-title":"S. Afr. J. Bot."},{"key":"ref_26","unstructured":"Akone, S.H. (2016). Secondary Metabolites from Fungi: Strategies of Activation of Silent Biosynthetic Pathways, Structure Elucidation and Bioactivity, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1039\/B819208A","article-title":"A chemical epigenetics approach for engineering the in situ biosynthesis of a cryptic natural product from Aspergillus niger","volume":"7","author":"Henrikson","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1093\/emboj\/cdg315","article-title":"The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2","volume":"22","author":"Zhu","year":"2003","journal-title":"EMBO J."},{"key":"ref_29","first-page":"1934578X1400900502","article-title":"Induced production of new diterpenoids in the fungus Penicillium funiculosum","volume":"9","author":"Liu","year":"2014","journal-title":"Nat. Prod. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1128\/EC.00186-07","article-title":"Histone deacetylase activity regulates chemical diversity in Aspergillus","volume":"6","author":"Shwab","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1128\/AAC.46.11.3532-3539.2002","article-title":"Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals: Correlation with reduction in CDR and ERG upregulation","volume":"46","author":"Smith","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"259","DOI":"10.5507\/bp.2011.033","article-title":"HDAC inhibitors sodium butyrate and sodium valproate do not affect human ncor1 and ncor2 gene expression in HL-60 cells","volume":"155","author":"Vrba","year":"2011","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1574-695X.2011.00780.x","article-title":"Novel bioactive metabolites producing endophytic fungus Colletotrichum gloeosporioides against multidrug-resistant Staphylococcus aureus","volume":"61","author":"Arivudainambi","year":"2011","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_34","unstructured":"Petrini, O. (1986). Microbiology of the Phyllosphere, Cambridge University Press."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gonzalez-Menendez, V., Perez-Bonilla, M., Perez-Victoria, I., Martin, J., Munoz, F., Reyes, F., Tormo, J.R., and Genilloud, O. (2016). Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes. Molecules, 21.","DOI":"10.3390\/molecules21020234"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1077159","DOI":"10.3389\/fgene.2022.1077159","article-title":"Secondary metabolites produced by endophytic fungi, Alternaria alternata, as potential inhibitors of the human immunodeficiency virus","volume":"13","author":"Nzimande","year":"2022","journal-title":"Front. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_38","first-page":"512","article-title":"Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees","volume":"10","author":"Tamura","year":"1993","journal-title":"Mol Biol. Evol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"783","DOI":"10.2307\/2408678","article-title":"Confidence limits on phylogenies: An approach using the bootstrap","volume":"39","author":"Felsenstein","year":"1985","journal-title":"Evolution"},{"key":"ref_40","unstructured":"Hsiang, S.-T. (2001, January 27\u201329). Embedded image coding using zeroblocks of subband\/wavelet coefficients and context modeling. Proceedings of the Proceedings DCC 2001, Data Compression Conference, Snowbird, UT, USA."},{"key":"ref_41","first-page":"540","article-title":"Ellagic acid & gallic acid from Lagerstroemia speciosa L. inhibit HIV-1 infection through inhibition of HIV-1 protease & reverse transcriptase activity","volume":"137","author":"Nutan","year":"2013","journal-title":"Indian J. Med. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1128\/AAC.46.6.1896-1905.2002","article-title":"Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy","volume":"46","author":"Wei","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8358","DOI":"10.1128\/JVI.74.18.8358-8367.2000","article-title":"Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120","volume":"74","author":"Derdeyn","year":"2000","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1128\/JVI.72.4.2855-2864.1998","article-title":"Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1","volume":"72","author":"Platt","year":"1998","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"eaba6617","DOI":"10.1126\/sciadv.aba6617","article-title":"Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency","volume":"6","author":"Stoszko","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"71","DOI":"10.13005\/bpj\/1862","article-title":"GC-MS analysed phyto-chemicals and antibacterial activity of Withania somnifera (L.) Dunal extract in the context of treatment to liver cirrhosis","volume":"13","author":"Mishra","year":"2020","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_47","unstructured":"(2022, October 12). Available online: https:\/\/www.nist.gov\/nist-research-library."},{"key":"ref_48","unstructured":"(2023, April 15). Available online: https:\/\/www.npatlas.org\/explore\/compounds\/NPA032343."},{"key":"ref_49","unstructured":"(2023, April 15). Available online: https:\/\/lotus.naturalproducts.net\/."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e70780","DOI":"10.7554\/eLife.70780","article-title":"The LOTUS initiative for open knowledge management in natural products research","volume":"11","author":"Rutz","year":"2022","journal-title":"eLife"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.2217\/epi-2016-0009","article-title":"LSD1: Biologic roles and therapeutic targeting","volume":"8","author":"Somervaille","year":"2016","journal-title":"Epigenomics"},{"key":"ref_52","unstructured":"National Center for Biotechnology Information (2023, April 22). PubChem Compound Summary for CID 18566, C.-, 2-Dicarbonitrile, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Cyclobutane-1_2-dicarbonitrile."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e202200020","DOI":"10.1002\/cmdc.202200020","article-title":"Cyclobutanes in small-molecule drug candidates","volume":"17","author":"Janssen","year":"2022","journal-title":"ChemMedChem"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s11743-001-0180-6","article-title":"Novel hydrolyzable and biodegradable cationic gemini surfactants: Bis (ester-ammonium) dichloride having a butenylene or a butynylene spacer","volume":"4","author":"Tatsumi","year":"2001","journal-title":"J. Surfactants Deterg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3073906","DOI":"10.1155\/2020\/3073906","article-title":"Mycochemical Screening and Analysis, Antioxidant Activity, and Biochemical Composition of Fermentation Strain Snef1216 (Penicillium chrysogenum)","volume":"2020","author":"Sikandar","year":"2020","journal-title":"J. Anal. Methods Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jtusci.2014.06.007","article-title":"In vitro antibacterial activity and gas chromatography\u2013mass spectroscopy analysis of Acacia karoo and Ziziphus mauritiana extracts","volume":"9","author":"Priyanka","year":"2015","journal-title":"J. Taibah Univ. Sci."},{"key":"ref_57","first-page":"99","article-title":"Antimicrobial activity and chemical constitutions of West Anatolian olive (Olea europaea L.) leaves","volume":"10","author":"Ceyhan","year":"2012","journal-title":"J. Food Agric. Environ."},{"key":"ref_58","first-page":"47","article-title":"Antioxidant and antibacterial activity of red seaweed Kappaphycus alvarezii against pathogenic bacteria","volume":"6","author":"Bhuyar","year":"2020","journal-title":"Glob. J. Environ. Sci. Manag."},{"key":"ref_59","first-page":"349","article-title":"Determination of 1, 2-Benzenedicarboxylic acid, bis (2-ethylhexyl) ester from the twigs of Thevetia peruviana as a Colwell Biomarker","volume":"2","author":"Save","year":"2015","journal-title":"J. Innov. Pharm. Biol. Sci."},{"key":"ref_60","first-page":"301","article-title":"GC-MS analysis of bioactive components of Hugonia mystax L.(Linaceae)","volume":"3","author":"Rajeswari","year":"2012","journal-title":"Res. J. Pharm. Biol. Chem. Sci."},{"key":"ref_61","first-page":"461","article-title":"Fungitoxic and cytotoxic activity of a novel compound 1,2-benzenedicarboxylic acid, diisooctyl ester of Plumbago zeylanica linn","volume":"8","author":"Rahman","year":"2006","journal-title":"Asian J. Microbiol. Biotechnol. Environ. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Li, M., Zhou, L., Yang, D., Li, T., and Li, W. (2012). Biochemical composition and antioxidant capacity of extracts from Podophyllum hexandrum rhizome. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-263"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kaviya, M., Balasubramanian, B., Bharathi, K., Malaisamy, A., Al-Dhabi, N.A., Mariadhas, V.A., Anand, A.V., and Liu, W. (2022). Evaluation of Nutritional Substances and Investigation of Antioxidant and Antimicrobial Potentials of Boerhavia diffusa with in Silico Molecular Docking. Molecules, 27.","DOI":"10.3390\/molecules27041280"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Hern\u00e1ndez, E., Balduque-Gil, J., Barriuso-Vargas, J.J., Casanova-Gasc\u00f3n, J., Gonz\u00e1lez-Garc\u00eda, V., Cuch\u00ed-Oterino, J.A., Lorenzo-Vidal, B., Mart\u00edn-Gil, J., and Mart\u00edn-Ramos, P. (2022). Holm Oak (Quercus ilex subsp. ballota (Desf.) Samp.) Bark Aqueous Ammonia Extract for the Control of Invasive Forest Pathogens. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911882"},{"key":"ref_65","first-page":"107","article-title":"Identification of some secondary metabolites produced by four Penicillium species","volume":"1","author":"Khani","year":"2014","journal-title":"Mycol. Iran."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5897\/JMPR2015.5993","article-title":"Schistosomicidal and molluscicidal activities of two Junipers species cultivated in Egypt and the chemical composition of their essential oils","volume":"10","author":"Ghaly","year":"2016","journal-title":"J. Med. Plants Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111630","DOI":"10.1016\/j.envres.2021.111630","article-title":"Bioremoval capacity of Co(+2) using Phormidium tenue and Chlorella vulgaris as biosorbents","volume":"204","author":"Sholkamy","year":"2022","journal-title":"Environ. Res."},{"key":"ref_68","first-page":"20","article-title":"Coumarin analogues as a potential inhibitor of leishmaniasis: A multi-targeting protein inhibition approach by molecular docking","volume":"4","author":"Kapoor","year":"2019","journal-title":"Univers. J. Pharm. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Cherne, M., Hall, J., Kellner, A., Chong, C., Cole, A., and Cole, A. (2019). Avirulins, a Novel Class of HIV-1 Reverse Transcriptase Inhibitors Effective in the Female Reproductive Tract Mucosa. Viruses, 11.","DOI":"10.3390\/v11050408"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Douka, M.D., and Litinas, K.E. (2022). An Overview on the Synthesis of Fused Pyridocoumarins with Biological Interest. Molecules, 27.","DOI":"10.3390\/molecules27217256"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9426","DOI":"10.3390\/molecules17089426","article-title":"Antifungal Activity of Salicylanilides and Their Esters with 4-(Trifluoromethyl)benzoic Acid","volume":"17","year":"2012","journal-title":"Molecules"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s10482-021-01598-4","article-title":"Novel Metabolites Identified From Bacillus Safensis and Their Antifungal Property against Alternaria alternata","volume":"114","author":"Prakash","year":"2021","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0031-9422(95)00234-X","article-title":"Phenylpropanoids and other secondary metabolites from fresh fruits of Picrasma quassioides","volume":"40","author":"Yoshikawa","year":"1995","journal-title":"Phytochemistry"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Tang, X.X., Liu, S.Z., Yan, X., Tang, B.W., Fang, M.J., Wang, X.M., Wu, Z., and Qiu, Y.K. (2019). Two New Cytotoxic Compounds from a Deep-Sea Penicillum citreonigrum XT20-134. Mar Drugs, 17.","DOI":"10.3390\/md17090509"},{"key":"ref_75","first-page":"1274","article-title":"Assessment of bioactive compounds in Brassica juncea using chromatographic techniques","volume":"7","author":"Sharma","year":"2018","journal-title":"J. Pharmacogn. Phytochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1016\/S2095-3119(18)62027-1","article-title":"Identification and characterization of Pichia membranifaciens Hmp-1 isolated from spoilage blackberry wine","volume":"17","author":"Ying","year":"2018","journal-title":"J. Integr. Agric."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1007\/s00203-021-02209-6","article-title":"GC\u2013MS analysis and molecular docking of bioactive compounds of Camellia sinensis and Camellia assamica","volume":"203","author":"Pradhan","year":"2021","journal-title":"Arch. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s00203-022-02949-z","article-title":"Antioxidant potential and molecular docking of bioactive compound of Camellia sinensis and Camellia assamica with cytochrome P450","volume":"204","author":"Pradhan","year":"2022","journal-title":"Arch. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1080\/10942912.2022.2070641","article-title":"Comparison of volatile compounds and fatty acids of jujubes (Ziziphus jujuba mill.) before and after blackening process","volume":"25","author":"Song","year":"2022","journal-title":"Int. J. Food Prop."},{"key":"ref_80","first-page":"56","article-title":"Characterization of alkaloid constitution and evaluation of antimicrobial activity of Solanum nigrum using gas chromatography mass spectrometry (GC-MS)","volume":"7","author":"Jasim","year":"2015","journal-title":"J. Pharmacogn. Phytother."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4103\/japtr.JAPTR_74_19","article-title":"Characterization, antioxidant, antimycobacterial, antimicrobial effcts of Moroccan rosemary essential oil, and its synergistic antimicrobial potential with carvacrol","volume":"11","author":"Chraibi","year":"2020","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"689527","DOI":"10.3389\/fmicb.2021.689527","article-title":"Antifungal Secondary Metabolites Produced by the Fungal Endophytes: Chemical Diversity and Potential Use in the Development of Biopesticides","volume":"12","author":"Xu","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_83","first-page":"1671","article-title":"Bioactive Secondary Metabolites Produced by the Fungal Endophytes of Conifers","volume":"10","author":"Stierle","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"540292","DOI":"10.1155\/2014\/540292","article-title":"Fungi treated with small chemicals exhibit increased antimicrobial activity against facultative bacterial and yeast pathogens","volume":"2014","author":"Zutz","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ameen, F., Almansob, A., Al Tami, M., Al-Enazi, N., Al-Sabri, A., and Orfali, R. (2021). Epigenetic Modifiers Affect the Bioactive Compounds Secreted by an Endophyte of the Tropical Plant Piper longum. Molecules, 26.","DOI":"10.3390\/molecules26010029"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Xue, M., Hou, X., Fu, J., Zhang, J., Wang, J., Zhao, Z., Xu, D., Lai, D., and Zhou, L. (2023). Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers. J. Fungi, 9.","DOI":"10.3390\/jof9020172"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e1800485","DOI":"10.1002\/cbdv.201800485","article-title":"How histone deacetylase inhibitors alter the secondary metabolites of Botryosphaeria mamane, an endophytic fungus isolated from Bixa orellana","volume":"16","author":"Triastuti","year":"2019","journal-title":"Chem. Biodivers."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"730355","DOI":"10.3389\/fmicb.2021.730355","article-title":"Epigenetic Modifiers Revamp Secondary Metabolite Production in Endophytic Nigrospora sphaerica","volume":"12","author":"Ramesha","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.chemosphere.2018.11.129","article-title":"Antifungal and anti-mycotoxin efficacy of biogenic silver nanoparticles produced by Fusarium chlamydosporum and Penicillium chrysogenum at non-cytotoxic doses","volume":"218","author":"Khalil","year":"2019","journal-title":"Chemosphere"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8211","DOI":"10.1038\/s41598-017-08673-9","article-title":"The antibacterial and antifungal activity of six essential oils and their cyto\/genotoxicity to human HEL 12469 cells","volume":"7","author":"Pangallo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_91","first-page":"60","article-title":"Antifungal activity of four plants against Alternaria alternata","volume":"18","author":"Rodino","year":"2014","journal-title":"Sci. Bull. Ser. F. Biotechnol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/6\/1404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:42:37Z","timestamp":1760125357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/6\/1404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,26]]},"references-count":91,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["microorganisms11061404"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11061404","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,26]]}}}