Introduction

The genus Streptomyces by far produces diverse secondary metabolites with various biological activities. Its complex morphological differentiation of Streptomyces, involving in the formation of a layer of hyphae, and signal molecule(s) production after cell wall breakdown may trigger the manufacture of different bioactive compounds (Chater and Chandra 2006). Moreover, Streptomyces can survive in assorted environments, which can stimulate a diverse secondary metabolites production. So far, over 600 species of Streptomyces have been recorded and proved to be the excellent sources of bioactive secondary metabolites (Genilloud et al. 2011). The terrestrial Streptomyces spp. have delivered multifarious chemical core-structures, such as linear polyketide (Raju et al. 2012), cyclobutane-bearing tricyclic lactam (Park et al. 2012), azoxide compounds (Ding et al. 2012), pyranonaphthoquinones (Wang et al. 2013), ansamysins (Lu et al. 2013), and sesquiterpene alblaflavenol B (Raju et al. 2015). In addition, several compounds have also been isolated from Streptomyces collected in various parts of Thailand, indicating a potential of Streptomyces as a source of bioactive compounds, for example, antimalarial C-glycosylated benz [α] anthraquinones (Supong et al. 2012), antimalarial samroiyotmycins A and B (Dramae et al. 2013), antibacterial streptophenazines (Bunbamrung et al. 2014), antimicrobial steffimycin C (Intaraudom et al. 2015).

In our continuing search for bioactive compounds from actinomycetes, we came across a terrestrial Streptomyces strain BCC71188, preliminarily identified by its morphology and 16S rRNA gene sequence analysis. The crude extract of the strain displayed a prolific secondary metabolic profile and exhibited antimicrobial activity against Bacillus cereus (MIC value 1.56 μg/ml), Mycobacterium tuberculosis (MIC 6.25 μg/ml), and Plasmodium falciparum (IC50 value 0.19 μg/ml). Therefore, the investigation was further conducted on identification of the strain by phenotypic chemotaxonomic and genotypic characteristics along with the isolation, structure elucidation, and biological evaluation of the secondary metabolites isolated from this strain.

Materials and methods

General experimental procedures

FT-IR spectra were measured on a Bruker ALPHA spectrometer. UV spectra were performed in MeOH on a Spekol 1200 spectrophotometer, Analytik Jena. Optical rotations were measured with JASCO P-1030 digital polarimeter. NMR spectra were recorded on Bruker Avance 500 MHz and Bruker Avance III 400 MHz NMR spectrometers using either acetone-d 6 or DMSO-d 6 as an internal standard. HRESIMS data were obtained from Bruker MicrOTOF spectrometer. Column chromatography was performed on Sephadex LH-20 column using 100 % MeOH as eluent. HPLC was performed on a Dionex-Ultimate 3000 series equipped with a binary pump, an autosampler, and diode array detector. Semi-preparative HPLC was performed on a Sunfire C18 column from Waters (5 μm, diam. 19 mm × 150 mm). Preparative HPLC was performed on a Sunfire C18 column from Waters (10 μm, diam. 19 mm × 250 mm).

Biological material

The actinomycete strain BCC71188 (original code KC138) was isolated from a soil sample collected from Nakhon Si Thammarat Province, Thailand, and deposited at BIOTEC Culture Collection (BCC), National Center for Genetic Engineering and Biotechnology (BIOTEC) with the registration number BCC71188. The 16S rRNA gene sequence (1346 nt) of this strain was deposited in DDBJ database with the accession number LC121598.

Isolation, characterization, and identification of actinomycete strain BCC71188

An actinomycete strain BCC71188 was isolated from a soil sample collected from Nakhon Si Thammarat Province, Thailand, and grown on a starch-casein nitrate agar, consisting of soluble starch 1 %, sodium caseinate 0.1 %, KH2PO4 0.05 %, MgSO4 0.05 %, and agar 1.8 % (pH 7.3). The agar plate was incubated at 30 °C for 21 days and actinomycete isolate was then purified on a ISP 2 agar medium, containing glucose 0.4 %, yeast extract 0.4 %, and malt extract 1 % (pH 7.3), at 30 °C in an incubator for 14 days. Then, the strain was grown on ISP 4 agar [containing soluble starch 1 %, K2HPO4 0.1 %, MgSO4 0.1 %, NaCl 0.1 %, (NH4)2SO4 0.2 %, CaCO3 0.2 %, and agar 1.8 % (pH 7.3)], incubated at 30 °C for 21 days, and observed by scanning electron microscopy (model JSM-5410 LV; JEOL). The carbon utilization of the strain was determined by using carbon utilization medium (ISP 9), consisting of 1 % sole carbon source (Shirling and Gottlieb 1966). The ISCC–NBS Color Charts standard sample no. 2106 was used for color designations (Kelly 1964). The tolerance of NaCl, pH, and the effect of temperature was determined by cultivating on ISP 2 medium. Gelatin liquefaction, nitrate reduction, and starch hydrolysis were determined by cultivation on various media, described by Arai (Arai 1975) and Williams and Cross (Williams and Cross 1971). For chemotaxonomic determination, dried cells of the strain were obtained from the cells grown in ISP 2 broth on a rotary shaker (200 rpm) at 30 °C for 4 days. Cells were then harvested by centrifugation, washed with distilled water, and freeze-dried. Cell wall peptidoglycan was prepared and hydrolyzed by the methods of Kawamoto et al. (Kawamoto et al. 1981) and the amino acid composition was analyzed by TLC (Staneck and Roberts 1974).

Genomic DNA extraction was performed from the cells grew in ISP 2 broth according to the method described by Tamaoka (1994). PCR-mediated amplification of the 16S rRNA gene was carried out as described by Inahashi et al. (Inahashi et al. 2010) and sequencing of the PCR products (Macrogen) was done by using universal primers (Lane 1991). The 16S rRNA gene sequence was multiply aligned with selected sequences obtained from the GenBank/EMBL/DDBJ databases by using CLUSTAL W program, version 1.81 (Thompson et al. 1994). The alignment was manually verified and adjusted prior to the construction of a phylogenetic tree. The phylogenetic tree was constructed by using the neighbor-joining (Saitou and Nei 1987) with the genetic distances calculated by Kimura’s 2-parameter model (Kimura 1980) in MEGA 6 software (Tamura et al. 2013). The confidence values for the branches of the phylogenetic tree were determined by using bootstrap analyses based on 1000 resamplings (Felsenstein 1985). 16S rRNA gene sequence similarities among the closely related strains were calculated manually after obtaining pair-wise alignments using CLUSTAL_X (Thompson et al. 1997).

Fermentation and isolation of secondary metabolites

The culture plate of strain BCC71188 was used for the stock culture, which grown on ISP 2 agar medium at 30 °C for 4 days. The stock culture was inoculated into 250-ml Erlenmeyer flasks, containing 150 ml of seed medium (ISP 2 broth). The seed culture of strain BCC71188 was cultivated on a rotary shaker (200 rpm) at 30 °C for 4 days. Then, the seed culture (20 flasks) was transferred into 80 × 1-l Erlenmeyer flasks, which each contained 250 ml of wheat germ-starch production medium, comprising (w/v) soluble starch 2 %, glycerol 0.5 %, defatted wheat germ 1 %, meat extract 0.3 %, yeast extract 0.3 %, and CaCO3 0.3 % (pH 7.3). The production culture (20 l) was cultivated for 14 days at 30 °C on rotary shakers (200 rpm). After 14 days of the cultivation, the whole culture was extracted three times with an equal volume of EtOAc and then the extract was dried over Na2SO4. EtOAc was evaporated to dryness to yield a crude extract (10.1 g), which was fractionated through a Sephadex LH-20 column to give seven fractions (F1–F7).

Fraction F1 (2.5 g) was purified by a preparative HPLC, eluted with a linear gradient system of 30–95 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to furnish compounds 3 (4.8 mg), 4 (0.10 g), and 6 (13.6 mg). Fraction F2 (1.2 g) was further purified by a preparative HPLC, eluted with a linear gradient system of 30–95 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to give two subfractions (F2F1-F2F2). Subfraction F2F1 (78.5 mg) was further purified by a preparative HPLC, eluted with a linear gradient system of 30–95 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to yield compounds 3 (4.7 mg) and 4 (17.8 mg). Subfraction F2F2 (47.6 mg) was further purified by semi-preparative HPLC, eluted with a linear gradient system of 45–95 % CH3CN in H2O over 35 min at the flow rate of 10 ml/min, to afford abierixin (11.1 mg) and 29-O-methylabierixin (13.6 mg).

Fraction F3 (0.8 g) was purified by a preparative HPLC, eluted with a linear gradient system of 45–95 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to give compound 9 (7.1 mg) and a mixture (35.9 mg). The mixture was purified by another semi-preparative HPLC, eluted with a linear gradient system of 40–95 % CH3CN in H2O over 35 min at the flow rate of 10 ml/min, to obtain compounds 4 (3.1 mg), 5 (4.7 mg), and 7 (11.2 mg).

Fraction F4 (2.9 g) was re-chromatographed on a Sephadex LH-20 column, eluted with 100 % MeOH to give two subfractions (F4F1-F4F2). Subfraction F4F1 (0.37 g) was purified by a preparative HPLC, eluted with a linear gradient system of 10–85 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to give compound 9 (3.2 mg). Subfraction F4F2 (1.1 g) was purified by a preparative HPLC, eluted with a linear gradient system of 10–95 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to yield compounds 1 (35.6 mg), 2 (4.1 mg), 7 (15.9 mg), 9 (15.2 mg), 14 (12.7 mg), and 17 (6.2 mg).

Fraction F5 (1.3 g) was re-chromatographed on another Sephadex LH-20 column to give two subfractions (F5F1-F5F2). Subfraction F5F1 (37.5 mg) was purified by a semi-preparative HPLC, eluted with a linear gradient system of 10–90 % CH3CN in H2O over 35 min at the flow rate of 10 ml/min, to afford compound 1 (15.4 mg). Subfraction F5F2 (0.50 g) was purified by a preparative HPLC, eluted with a linear gradient system of 10–95 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to afford compounds 14 (20.9 mg), 15 (10.2 mg), and 16 (10.9 mg).

Fraction F6 (1.1 g) was re-chromatographed on a Sephadex LH-20 column, to give three subfractions (F6F1-F6F3). Subfraction F6F1 (65.5 mg) was purified by preparative HPLC, eluted with a linear gradient system of 30–80 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to obtain compounds 10 (47.5 mg) and 11 (6.1 mg). Subfraction F6F2 (0.50 g) was purified by a semi-preparative HPLC, eluted with a linear gradient system of 50–90 % CH3CN in H2O over 30 min at the flow rate of 10 ml/min, to yield compounds 15 (10.2 mg) and 16 (17.5 mg). Subfraction F6F3 (0.83 g) was purified by a preparative HPLC, eluted with a linear gradient system of 10–80 % CH3CN in H2O over 40 min at the flow rate of 15 ml/min, to give compounds 4 (4.6 mg), 10 (28.8 mg), 12 (7.2 mg), 13 (16.1 mg), and 14 (34.7 mg). In addition, compound 9 (6.9 mg) was obtained from the fraction F7 by a semi-preparative HPLC, eluted with a linear gradient system of 10–70 % CH3CN in H2O over 30 min at the flow rate of 10 ml/min.

Monoglycosylelaiolide (3): Colorless solid; [α]D 27 + 6.3 (c 0.12, MeOH); UV λ max (log ε, MeOH) 249 (4.22) nm; IR (ν max, cm−1) 34,251, 2967, 2933, 1696, 1638, 1462, 1384, 1304, 1282, 1261, 1224, 1183, 1149, 1112, 1087, 1017, 1001, 902, 879, 803, and 755; 1H (500 MHz) and 13C NMR (125 MHz) data in acetone-d 6 (see Table 1, Figs. S1–S6); HRESIMS m/z 917.5241 [M + Na]+ (calcd. for C48H78O15Na, 917.5233).

Table 1 The 1H and 13C NMR spectral data of compound 3 (monoglycosylelaiolide)
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2-Amino-6-hydroxyl-7-methyl-1,4-naphthoquinone (8): Red solid; UV λ max (log ε, MeOH) 222 (4.08), 272 (4.08), 276 (4.08), and 324 (3.92) nm; IR (ν max, cm−1) 3464, 3352, 2924, 2854, 1683, 1621, 1597, 1562, 1467, 1341, 1300, 1213, 1160, 1071, 1040, 1011, and 827; 1H NMR (400 MHz, DMSO-d 6) (Figs. S7 and S10) 2.19 (s, 7-CH3), 5.67 (s, H-3), 7.10 (br s, OH), 7.26 (s, H-5), 7.69 (s, H-8); 13C NMR (100 MHz, DMSO-d 6) (Figs. S8 and S10) 16.3 (7-CH3), 101.8 (3-CH), 111.3 (5-CH), 122.4 (8a-C), 128.7 (7-C), 129.5 (8-CH), 134.5 (4a-C), 151.2 (2-C), 162.5 (6-C), 180.9 (1-C), 182.4 (4-C); HRESIMS m/z 202.0514 [M − H]− (calcd. for C11H8O3N, 202.0510).

Bioassays

Antibacterial activity against B. cereus was tested by resazurin microplate assay (REMA) (Sarker et al. 2007). Vancomycin was used as a positive control. The green fluorescent protein microplate assay (GFPMA) was used for evaluation of cytotoxicity against Vero cell (African green monkey kidney fibroblasts, ATCC CCL-81) and of antituberculosis against M. tuberculosis strain H37Ra (Changsen et al. 2003). Ellipticine was used as a positive control for cytotoxicity against Vero cell. Isoniazid, ofloxacin, rifampicin, streptomycin, and ethambutol were used as the positive controls for antitubercular activity. Antimalarial assay against P. falciparum (K-1, multidrug-resistant strain) was performed by using the microculture radioisotope technique (Desjardins et al. 1979). Dihydroartemisinin and mefloquine were used as positive controls for antimalarial assay. Cytotoxicity against KB (oral human epidermoid carcinoma, ATCC CCL-17), MCF-7 (human breast cancer, ATCC HTC-22), and NCI-H187 (human small-cell lung cancer, ATCC CRL-5804) cell lines were evaluated by using the resazurin microplate assay (REMA) (O’Brien et al. 2000). Ellipticine and doxorubicin were used as the positive controls for anti-KB activity. Tamoxifen and doxorubicin were used as the positive controls for anti-MCF-7 activity. Doxorubicin was used as a positive control for anti-NCI-H187 activity. Minimum inhibitory concentration (MIC) represents the lowest concentration that inhibited 90 % growth of bacteria and IC50 represents the concentration that caused 50 % reduction in cell growth.

Results

Identification and characterization of actinomycete strain BCC71188

Based on morphology, the strain produced grayish yellow substrate mycelium and greenish gray aerial mycelium on ISP 2 agar. The spiral chain spore was developed on the aerial mycelium. The surface of the spores was rough (Fig. 1). Strain BCC71188 grew well on ISP 2, ISP 3, ISP 4, ISP 5, ISP 6, ISP 7, and nutrient agars. The strain could utilize L-arabinose, D-fructose, D-glucose, D-mannitol, D-melibiose, myo-inositol, raffinose, L-rhamnose, and D-xylose as carbon sources. The strain could hydrolyze soluble starch, peptonize milk, and reduce nitrate to nitrite. Strain BCC71188 could grow on the medium in a presence of salt 0–4 % (w/v) NaCl, at pH 5–12, and at temperature in a range of 15–40 °C. For cell wall analysis, the isomer of diaminopimelic acid (DAP) in the peptidoglycan was identified as LL-DAP. Based on morphological and pattern of LL-DAP, the strain BCC71188 was identified as a member in the family Streptomycetaceae. In addition, the strain did not show diagnostic sugars in whole-cell hydrolysates and contained phospholipid type II, indicating that the strain BCC71188 could be classified as the genus Streptomyces (Manfio et al. 1995).

Fig. 1
figure 1

Colony characteristic of strain BCC711888 appearance on ISP 3 (a) and scanning electron micrograph on ISP 4 (b)

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The 16S rRNA gene sequence (1346 nt) of strain BCC71188 was deposited in DDBJ database with the accession number LC121598. The sequence analysis indicated that BCC71188 was closely related to the genus Streptomyces and showed high level of similarity values compared with Streptomyces samsunensis M1463T (99.85 %) and Streptomyces malaysiensis NBRC 16446T (99.40 %). In addition, neighbor-joining phylogenetic tree, constructed based on 16S rRNA gene sequences and its closest relatives, also confirmed that the strain belonged to the genus Streptomyces that formed the subclade and clustered with S. samsunensis M1463T and S. malaysiensis NBRC 16446T (Fig. 2). The strain was deposited at BIOTEC Culture Collection (BCC), National Center for Genetic Engineering and Biotechnology (BIOTEC) with the registration number BCC71188.

Fig. 2
figure 2

Neighbor-joining phylogenetic tree based on 16S rRNA gene sequences of the strain BCC71188 and closely related Streptomyces strains. The numbers on the branches indicate the percentage bootstrap values of 1000 replicates; only values >50 % are indicated

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Isolation and structure elucidation of secondary metabolites from the strain BCC71188

An EtOAc crude extract was purified on a Sephadex LH-20 column and followed by HPLC to yield 19 compounds, including cyclic peptides (1 and 2), macrolide alaiophylin derivatives (3–7), naphthoquinone (8), nahuoic acid C (9), geldanamycin analogs (10–13), diterpene cyclooctatin (14), polyketide germicidins B (15) and A (16), a peptide actinoramide A (17), and two polyethers (abierixin, and 29-O-methylabierixin). The chemical structures of these compounds were determined by using spectroscopic techniques including NMR, Mass, IR, UV spectroscopy, and the isolated compounds were also evaluated for biological activity.

Compound 3 was obtained as a white solid. The molecular formula C48H78O15 was deduced by the analysis of HRESIMS spectrum, giving the mass ion peak at m/z 917.5241 [M + Na]+. Partial spectroscopic information from the 1H and 13C NMR spectra data were identical to those reported for monoglycosylelaiolide (Table 1), which was synthesized from elaiophylin (Bindseil and Zeeck 1993). This is the first report of monoglycosylelaiolide from a natural source. The complete 1H and 13C NMR spectral data were given in Table 1.

Compound 8 was obtained as a red solid and had the molecular formula of C11H9 NO3 by showing a mass ion peak at m/z 202.0514 [M − H]− in HRESIMS spectrum (Fig. S12). The 1H NMR spectrum gave signals of one methyl at δH 1.44 (s) and three aromatic protons at δH 5.67 (s), 7.26 (s), and 7.69 (s). The 13C NMR spectrum (Fig. S8), together with DEPT-135 spectrum (Fig. S9), displayed 11 signals comprising one methyl (δC 16.3), three aromatic methine (δC 101.8, 111.32, 129.5), seven sp2 quaternary (δC 122.4, 128.7, 134.5, 151.2, 162.5, 180.9, 182.4) carbons. Two sp2 quaternary carbons resonating at δC 180.9 and 182.4 were carbonyl carbons of 1,4-naphthoquinones, supported by the absorption at ν max 1683 cm−1 in IR spectrum. The HMBC spectrum (Fig. S11), showed correlations from the methyl proton at 7-CH3 (δH 1.44) to C-6, C-7, and C-8; from H-8 (δH 7.69) to C-1, C-4a, C-6, and 7-CH3; from H-5 (δH 7.26) to C-4, C-6, C-7, C-8a; from H-3 (δH 5.67) to C-1, C-2, and C-4a. In the 13C NMR spectrum, C-2 and C-6 resonated at δC 151.2 and δC 162.5, respectively, together with HRESIMS data, suggested the presence of an amino and a hydroxyl groups at C-2 and C-6, respectively. Therefore, compound 8 was 2-amino-6-hydroxyl-7-methyl-1,4-naphthoquinone and possessed the chemical structure as shown in Fig. 3. Compound 8 is a new 1,4-naphthoquinone derivative with a presence of amino group at the 2 position.

Fig. 3
figure 3

Chemical structures of secondary metabolites isolated from the strain BCC71188

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The 1H and 13C NMR spectral data of the known compounds (1, 2, 4–7, 9–17, abierixin, and 29-O-methylabierixin) were agreed with those previously reported for nocardamine (1) (Lee et al. 2005), dehydroxynocardamine (2) (Lee et al. 2005), elaiophylin or azalomycin (4) (Kaiser and Keller-Schierlein 1981; Nair et al. 1994), 11, 11′-O-dimethylelaiophylin (5) (Ritzau et al. 1998; Wu et al. 2013), efomycin G (6) (Frobel et al. 1990), oxohygrolidin (7) (Carr et al. 2010; Kretschmer et al. 1985), nahuoic acid C (9) (Nong et al. 2016), geldanamycin (10) (DeBoer et al. 1970), 17-O-demethylgeldanamycin (11) (Yin et al. 2011), 17-demethoxyreblastatin (12) (Stead et al. 2000), 4,5-dihydrothiazinogeldanamycin (13) (Wu et al. 2012), cyclooctatin (14) (Aoyagi et al. 1992; Zhao et al. 2013), germicidins B (15) and A (16) (Petersen et al. 1993), actinoramide A or padanamide A (17) (Nam et al. 2011), abierixin, and 29-O-methylabierixin (Supong et al. 2016). The absolute configuration at the asymmetric carbon of compound 16 was determined to be “S” as giving a positive sign of specific rotation (\( {\left[\alpha \right]}_D^{24} \) +27.86, MeOH), versus the specific rotation ([α] D +22.0, MeOH) reported in the literature (Aoki et al. 2011). In addition, these previously reported compounds were also confirmed by HRESIMS data, their physico-chemical properties, and chemical means for compound 9.

The results showed that Streptomyces sp. strain BCC71188 is as an excellent producer of secondary metabolites. The strain provided two naturally new compounds, which were compounds 3 and 8, and also produced diverse compounds that derived from different biosynthetic pathways.

Biological activity of isolated compounds

Nocardamine analogs 1 and 2 exhibited antimalarial activity against P. falciparum, K-1 strain—the multidrug-resistant strain, with IC50 values of 3.20 and 2.63 μg/ml, respectively, and also showed cytotoxicity against NCI-H187 cell line with IC50 values of 17.76 and 9.16 μg/ml, respectively. Moreover, elaiophylin derivatives 4–6 displayed antimicrobial activity against B. cereus (MIC 0.78 3.13 μg/ml), M. tuberculosis (MIC 0.78 12.0 μg/ml), and P. falciparum (IC50 0.22 2.37 μg/ml), while monoglycosylelaiolide (3) showed only antimalarial activity with IC50 value of 2.46 μg/ml. However, compounds 3–6 also showed cytotoxicity against both cancerous and non-cancerous cells (Table 2). Geldanamycin derivatives (10–12) showed antimalarial activity with IC50 values in a range of 0.31–1.90 μg/ml. Compound 10 had strong cytotoxicity against both cancerous and non-cancerous cells (Table 2), while compounds 11 and 12 displayed non-cytotoxicity against KB and MCF-7 cells. Cyclooctatin (14) showed antimicrobial activity against B. cereus (MIC 25.0 μg/ml) and P. falciparum (IC50 7.14 μg/ml) with relatively low cytotoxicity. Moreover, compounds 8, 9, 13, 15, and 16 were inactive for all tests except that compound 9 displayed low cytotoxicity against NCI-H187 cell line with IC50 value of 28.53 μg/ml. Compound 7, abierixin, and 29-O-methylabierixin were earlier reported from our group for antimicrobial activity against B. cereus, M. tuberculosis, and P. falciparum along with the cytotoxicity against both cancerous and non-cancerous cells (Supong et al. 2016).

Table 2 Biological activity of isolated compounds from Streptomyces sp. BCC71188
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Discussion

The genus Streptomyces is the major group of filamentous actinobacteria that has been isolated from various environments. An ability to produce bioactive compounds, especially antibiotics, of this genus is well recognized. An actinomycetes strain BCC71188 was identified by its morphological, chemotaxonomic, and genotypic characteristics as Streptomyces, which closely related to S. samsunensis M1463T (99.85 %) and S. malaysiensis NBRC 16446T (99.40 %). The crude extract of this strain exhibited strong antimicrobial activity including anti-B. cereus (MIC 1.56 μg/ml), anti-M. tuberculosis (MIC 6.25 μg/ml), and anti-P. falciparum (IC50 0.19 μg/ml). Nineteen compounds, including two naturally new and 17 known, have been isolated and identified from Streptomyces sp. BCC71188. Nocardamine or deferrioxamine E (1) was originally reported from various strains of bacteria such as Nocardia sp., Pseudomonas stutzeri, and S. hydroscopicus var. geldanus (Lee et al. 2005; Maehr et al. 1977; Wang et al. 2000). Dehydroxynocardamine or terragine E (2) was earlier isolated from engineered S. lividans (Wang et al. 2000) and later isolated from a marine-derived bacterium of the genus Streptomyces (Lee et al. 2005) and S. avermitilis K139 (Ueki et al. 2009). Compounds 1 and 2 were inactive against various strains of Gram-positive and Gram-negative bacteria at the concentration of 200 μg/ml and several fungal strains (Lee et al. 2005). Monoglycosylelaiolide (3) was semi-synthesized from elaiophylin (Bindseil and Zeeck 1993) and its biological activity has never been reported. Elaiophylin or azalomycin B or gopalamycin (4) and 11,11′-O-dimethylelaiophylin (5) was formerly isolated from S. melanosporus, S. violaceoniger (Arai 1960) and Streptomyces spp. strains HKI-0113 and HKI-0114 (Ritzau et al. 1998). Compounds 4 and 5 had antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, Streptococcus pyogenes, Streptococcus faecium with MIC in a range of 0.78–3.13 μg/ml (Hammann et al. 1990) and also showed cytotoxicity against L-929, K562, and HeLa cell lines (Ritzau et al. 1998). Efomycin G (6) was formerly isolated from soil Streptomyces sp. BS 1261 (Frobel et al. 1990), from the marine-derived Streptomyces sp. 7-145 (Wu et al. 2013), and from endophytic Streptomyces sp. BCC72023 (Supong et al. 2016). It displayed antimicrobial activity with cytotoxicity against both cancerous and non-cancerous cells (Supong et al. 2016; Wu et al. 2013). Oxohygrolidin (7) was isolated from Streptomyces spp. from various sources (Kretschmer et al. 1985; Supong et al. 2016) and antimicrobial activity was also reported (Supong et al. 2016). Nahuoic acid C (9), a polyketide with a decalin ring, was first isolated from the marine Streptomyces SCSGAA 0027 (Nong et al. 2016) and was failed to display biological activity including acetylcholinesterase assay, antibacterial assay, and cytotoxicity against several cancer cell lines such as H1975, K562, BGC823, MCF-7, HL60, and Huh-7 (Nong et al. 2016). However, it had weak cytotoxicity against NCI-H187 (IC50 28.53 μg/ml, Table 2). Geldanamycin analogs with varying substituents at the C-17, such as tanespimycin (or 17-N-allylamino-17-demethoxygeldanamycin, 17-AAG), have been developed for anticancer agents due to their ability to inhibit the chaperone activity of heat shock protein 90 (Hsp90) (Lin et al. 2011). Due to the limitation on the hepatotoxicity and low water solubility, more analogs of geldanamycin are, therefore, required for further study. Geldanamycin (10) was previously isolated from S. hygroscopicus var. geldanus var. nova and had broad spectrum of antimicrobial activity (MIC 2 – >100 μg/ml), showed anti-phytopathogenic fungal activity against Alternaria, Pythium, Botrytis, and Penicillium (<500 ppm), and possessed strong anticancer activity against KB and L1210 cells (DeBoer et al. 1970). 17-O-demethylgeldanamycin (11) was first reported from S. autolyticus CGMCC 0516 with inactivated the gdmMT gene to study gene encoding C-17 O-methyltransferase of geldanamycin biosynthesis (Yin et al. 2011). Moreover, this is the first report of compound 11 directly obtained from a natural source and it exhibited antimalarial activity (IC50 1.90 μg/ml) and anti-NCI-H187 activity (IC50 1.11 μg/ml). 17-Demethoxylreblastatin (12) was formerly isolated from Streptomyces sp. S6619 and S. hygroscopicus JCM4427 (Wu et al. 2012). Compound 12 inhibited oncostatin M (OSM)-driven sPAP (secreted placenta alkaline phosphatase) production in HepG2B6 cells with IC50 value of 0.7 mM (Stead et al. 2000) and Hsp90 ATPase with IC50 value of 1.82 μM (Wu et al. 2012). Compound 13, geldanamycin with a thiazino-moiety in hydroquinone ring at C-19, was first isolated from the gdmP mutant in Streptomyces hygroscopicus 17997 (Lin et al. 2011) and later from S. hygroscopicus JCM4427 (Wu et al. 2012). It had 33-fold higher water solubility than compound 10 and possessed moderate anti-HSV-1 virus activity toward infected Vero cells with IC50 value of 0.252 μM (Lin et al. 2011). Compound 13 was inactive to all our biological tests (Table 2). Cyclooctatin (14), a tricyclic diterpene with 5-8-5-fused ring system, was previously isolated from Streptomyces spp., such as S. melanosporofaciens MI614-43F2 (Aoyagi et al. 1992) and Streptomyces sp. LZ35 (Zhao et al. 2013), and was inactive toward antimicrobial activity at 100 μg/ml but inhibited lyso-phospholipase enzyme with low cytotoxicity in mice (Aoyama et al. 1992). Moreover, in our assay, compound 14 exhibited weak antimalarial (IC50 7.14 μg/ml) and anti-B. cereus (MIC 25.0 μg/ml) activities (Table 2). Pyrone derivatives known as germicidins B (15) and A (16) were formerly isolated from S. viridochromogens NRRL B-1551 (JCM4265) (Petersen et al. 1993) and S. coelicolor A3(2) (Aoki et al. 2011). Compound 16 inhibited spore germination of several Streptomyces strains at a concentration of 40 pg/ml (Petersen et al. 1993) and of the producing strain at concentration above 1 μg/ml (Aoki et al. 2011). In addition, germicidin A (16) was inactive against various Gram-positive and Gram-negative bacteria and various fungi (Petersen et al. 1993). Actinoramide A or padanamide A (17), having a unique embodiment of the unusual amino acids, was earlier isolated from a marine bacterium, which closely related to the genus Streptomyces spp. (Nam et al. 2011; Williams et al. 2011) and showed cytotoxic to Jurkat T lymphocyte cells (ATCC TIB-152) in vivo with IC50 value of 60 μg/ml (Williams et al. 2011). However, compound 17 was inactive against HCT-116 (human colon carcinoma) cells, methicillin-resistant S. aureus, and the breast cancer-related enzyme aromatase (Nam et al. 2011). Abierixin and 29-O-methylabierixin were previously produced by various Streptomyces spp. such as S. albus NRRL B-1865 (David et al. 1985), S. hygroscopicus XM201 (Wu et al. 2009), and endophytic Streptomyces sp. BCC72023 (Supong et al. 2016) and was earlier reported by our group to exhibit antimicrobial activity with weak cytotoxicity (Supong et al. 2016).