Isolation, Purification, and Characterization of Five Active Diketopiperazine Derivatives from Endophytic Streptomyces SUK 25 with Antimicrobial and Cytotoxic Activities

Abstract

In our search for new sources of bioactive secondary metabolites from sp., the ethyl acetate extracts from endophytic SUK 25 afforded five active diketopiperazine (DKP) compounds. The aim of this study was to characterize the bioactive compounds isolated from endophytic SUK 25 and evaluate their bioactivity against multiple drug resistance (MDR) bacteria such as and spp., and their cytotoxic activities against the human hepatoma (HepaRG) cell line. The production of secondary metabolites by this strain was optimized through Thornton's medium. Isolation, purification, and identification of the bioactive compounds were carried out using high-performance liquid chromatography, high-resolution mass liquid chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance, and cryopreserved HepaRG cells were selected to test the cytotoxicity. The results showed that endophytic SUK 25 produces four active DKP compounds and an acetamide derivative, which were elucidated as -(-Val--Pro), -(-Leu--Pro), -(-Phe--Pro), -(-Val--Phe), and -(7-hydroxy-6-methyl-octyl)-acetamide. These active compounds exhibited activity against methicillin-resistant S. aureus ATCC 43300 and, with low toxicity against human hepatoma HepaRG cells. Endophytic SUK 25 has the ability to produce DKP derivatives biologically active against some MDR bacteria with relatively low toxicity against HepaRG cells line.

Streptomyces sp. MUM273b: A mangrove‐derived potential source for antioxidant and UVB radiation protectants

“…In line with several previous studies, these groups of chemicals were also reported in the bacterial fermentation broth or extracts derived from Actinomycetes and Streptomyces sp. For instance, dimethyltrisulfide ( 1 ) (Groenhagen, Maczka, Dickschat, & Schulz, ), trimethylpyrazine ( 2 ) (Citron, Barra, Wink, & Dickschat, ), 2‐acetylpyrrole ( 3 ) (Morgenstern, Paetz, Behrend, & Spiteller, ), pyrazine,2,5‐dimethyl‐3‐(3‐methylbutyl) ( 4 ) (Citron et al, ), phenol,2,4‐bis(1,1‐dimethylethyl)‐ ( 8 ) (Kumar, Duraipandiyan, & Ignacimuthu, ), benzoic acid,4‐ethoxy‐,ethyl ester ( 9 ) (Sharma, Goel, Dureja, & Uniyal, ), (3R,8aS)‐3‐methyl‐1,2,3,4,6,7,8,8a‐octahydropyrrolo[1,2a]pyrazine‐1,4‐dione ( 13 ) (Tan et al, ), pyrrolo[1,2a]pyrazine‐1,4‐dione, hexahydro ( 14 ) (Ser, Palanisamy, et al, ), 1,4‐diaza‐2,5‐dioxo‐3‐isobutyl bicyclo[4.3.0]nonane ( 15 ) (Ser, Ab Mutalib, et al, ), 9H‐Pyrido[3,4‐b]indole ( 16 ) (Tan, Ser, et al, ), 2,5‐piperazinedione, 3‐(1‐methylethyl)‐6‐(phenylmethyl)‐ ( 17 ) (Alshaibani et al, ), 3‐benzyl‐1,4‐diaza‐2,5‐dioxobicyclo[4.3.0]nonane ( 18 ) (Jog, Pandya, Nareshkumar, & Rajkumar, ; Sharma, Kalita, & Thakur, ) and phenol,2,2′‐methylenebis[6‐(1,1‐dimethylethyl)‐4‐methyl‐ ( 19 ) (Tan, Ser, et al, ).…”

Concepts and Methods to Access Novel Antibiotics from Actinomycetes

“…Liquid and gas chromatography are irreplaceable instruments for the separation of highly complex bacterial crude extracts [ 261 , 262 , 263 ]. Another evolving analytical separation technique that has already proven its impact in phytochemistry is supercritical fluid chromatography (SFC) [ 264 ].…”

Antibacterial activity of Cordyline fruticosa leaf extracts and its endophytic fungi extracts

“…Based on ethnobotanical information, C. fruticosa is used as a hemostatic and also used to treat diarrhea, sore throat, neck pain, toothache, laryngitis, and mammary gland infections (Fouedjou et al 2014;Fouedjou et al 2016). Plants used in traditional medicine around the world are studied for their ability as host for endophytic fungi that have antimicrobial potential, and recent developments reported that endophytic fungi are a potential reservoir of bioactive compounds useful for medicinal exploitation (Alshaibani et al 2017;Liang et al 2012;Chi et al 2019).…”