Recent Advances in the Discovery of Bioactive Metabolites from Pestalotiopsis
Total Page：16
File Type：pdf, Size：1020Kb
Phytochem Rev DOI 10.1007/s11101-017-9495-3 Recent advances in the discovery of bioactive metabolites from Pestalotiopsis Sunil Kumar Deshmukh . Ved Prakash . Nihar Ranjan Received: 19 November 2016 / Accepted: 14 February 2017 Ó Springer Science+Business Media Dordrecht 2017 Abstract Fungal endophytes have marked a signif- Keywords Pestalotiopsis Á Endophytes Á Drug icant impact on drug discovery reducing the burden discovery Á Natural products Á Anticancer agents Á and dependency on plants. The vast diversity of Taxol Pestalotiopsis sp. has emerged as promising source of wide range of bioactive natural compounds. Recently a series of numerous novel secondary metabolites Introduction have been discovered of which taxol has drawn attention of scientific community towards its medic- Endophytic fungi have been area of wide research for inal potential. A wide variety of compounds like their unexplored potential in the discovery of bioactive alkaloids, polyketides, terpenoids, flavonoids, cou- compounds. The genus Pestalotiopsis was established marins, xanthones, quinones, semiquinones, peptides, by Steyaert in 1949, following a taxonomic amend- phenols, phenolic acids, and lactones have been ment to the genus Pestalotia (Steyaert 1949, 1953a, b). identified which have usage as antimicrobial, antifun- To date, 234 described species of Pestalotiopsis that gal, antiviral antoneoplastic, and antioxidant activi- are differentiated on conidial characteristics are listed ties. This review aims to highlight recent discoveries in Index Fungorum (http://www.indexfungorum.org/ of different strains of Pestalotiopsis identified for Names/Names.asp). Pestalotiopsis species (Amphis- producing natural bioactive compounds along with phaeriaceae) are widely distributed in nature of which insights of their source of origin and potential in many are saprobes, while others are either pathogenic biotechnological applications. or endophytic to living plants (Jeewon et al. 2003). Pestalotiopsis is a widespread genus, usually endo- phytic, occurring in a wide range of substrata which S. K. Deshmukh (&) Á N. Ranjan (&) have attracted attention for their ability to produce a TERI–Deakin Nano Biotechnology Centre, The Energy variety of bioactive secondary metabolites. Chemical and Resources Institute, Darbari Seth Block, IHC Complex, Lodhi Road, New Delhi 110003, India studies of the fungal genus Pestalotiopsis have affor- e-mail: [email protected] ded a variety of bioactive natural products (Yang et al. N. Ranjan 2012). To underline its potential, over seventy new e-mail: [email protected] bioactive secondary metabolites have been isolated from Pestalotiopsis fici which is now one of the pro- V. Prakash lific producers of novel natural products (Liu 2011). In Department of Biotechnology, College of Engineering and Technology, IILM-Academy of Higher Learning, recent years, Pestalotiopsis, has gained considerable Greater Noida 201306, India attention (Xu et al. 2010). Since the discovery of taxol, 123 Phytochem Rev an anticancer agent, from an endophytic fungal strain Pestalofones A, B, C and E (4–7) (Fig. 1) were Pestalotiopsis microspora (Strobel et al. 1996), sig- isolated from this fungus. The chemical structure nificant interest has been generated in the search of determination was done using standard one and two- bioactive compounds from this genus. This review dimensional spectroscopic techniques. Compounds (4, aims to highlight the different strains of Pestalotiopsis 5 and 7) showed inhibitory effects on HIV-1 replica- identified for their various bioactive roles. Special tion in C8166 cells, with EC50 values of 90.4, 64.0, and emphasis has been put to detail their source of origin, 93.7 lM, respectively (all three compounds showed functions and their biological roles. CC50 values of greater than 200 lM; the positive control indinavir sulfate showed an EC50 value of 8.81 nM). Pestalofone C (6) and E (7) also showed Taxol producing Pestalotiopsis species significant antifungal activity against Aspergillus fumigatus, with IC50/MIC values of 1.10/35.3, 0.90/ Paclitaxel (taxol) (1) (Fig. 1), a well-known and 31.2 lM, respectively (the positive control flucona- highly functionalized tetracyclic diterpenoid bioactive zole showed IC50/MIC values of 7.35/163.4 lM) (Liu compound, was isolated from the bark of Taxus et al. 2009a). brevifolia (Wani et al. 1971). Taxol is found in Liu et al. (2011a) isolated Pestalofone F (8) and extremely low amounts in the needles, bark, and roots Pestalodiol C (9) (Fig. 1) from P. fici isolated from the of yews (Taxus sp.). It is specifically targeted to treat branches of C. sinensis. Compound (8) displayed prostate, ovarian, breast, and lung cancers (Rowinsky cytotoxicity against HeLa and MCF-7 cells with IC50 1997). Taxol stabilizes plus end dynamic instability of values of 14.4 and 11.9 lM, respectively and Pestalo- microtubules both in vitro and in vivo (Jordan et al. diol C displayed cytotoxicity against the HeLa and 1993; Yvon 1999). The discovery of a paclitaxel- MCF-7 cells, with IC50 values of 16.7 and 57.5 lM, producing endophytic fungus Taxomyces andreanae respectively. Pestalofone J (10), and K (11) (Fig. 1) from the Pacific yew (T. brevifolia) by Stierle et al. were obtained from P. fici isolated from the branches (1993) generated immense interest in the scientific of C. sinensis. Using a combination of 1D, 2D NMR community for the isolation of endophytic fungi, (1H-1H COSY, HMBC, and NOESY) and mass which produce several other active metabolites. spectroscopic techniques, the chemical structure was Paclitaxel and its analogues such as baccatin III (2) determined. Compound (10) showed weak cytotoxic and 10-deacetylbaccatin III (3) (Fig. 1) have been activities against HeLa, T24, A549, and MCF-7 cell reported from a large number of endophytic fungi lines with IC50 values of 44.3, 39.3, 35.3, and (Zhao et al. 2011). Table 1 provides a comprehensive 38.3 lM, respectively. Compound (11) was also found list of taxol-producing species from the genus to have weak cytotoxic activities against HeLa, T24, Pestalotiopsis. As shown in Table 1, taxol is produced A549, and MCF-7 cell lines, with IC50 values 65.5, by a large number of species of the same genus 45.7, 58.9, and 29.2 lM, respectively (the positive (Pestalotiopsis) suggesting similarity of pathways in control cisplatin showed the IC50 values of 7.4, 3.9, their production. 8.4, and 6.4 lM, respectively) (Wang et al. 2016). Chloropupukeananin (12) (Fig. 1) was another bioactive compound isolated from the same fungus. Bioactive metabolites from Pestalotiopsis fici Proton COSY analysis of this compound revealed the presence of two different sets of proton spin systems Endophytic fungus Pestalotiopsis fici from the and further analysis using HMBC indicated the branches of an unidentified tree in the suburb of presence of methyl benzoate unit in this isolate. Using Hangzhou (China) was found to be highly favorable HMBC correlation and single crystal X-ray diffrac- for producing novel natural products. Liu (2011a) has tion, the structure of compound 12 was unambigu- reviewed the work on compounds reported from this ously assigned with defined stereochemistry at all the particular fungus. Seventy new bioactive secondary chiral centers. Compound (12) showed an inhibitory metabolites have been reported by in-depth chemical effect on HIV-1 replication in C8166 cells, with an studies. Some representative metabolites identified IC50 value of 14.6 lM, and it also displayed cytotoxic from the Pestalotiopsis fici are reported here. effect against HeLa and HT29 cells, showing IC50 123 Phytochem Rev Fig. 1 Chemical structures of Taxol and its analogs (1–3) and metabolites isolated from the genus Pestalotiopsis fici 123 Phytochem Rev Fig. 1 continued values of 1.4 and 6.7 lM, respectively. In addition, fragments of a tricyclo[4.3.1.03,7]decane, an aniso- modest antimicrobial activity was also observed for prenylated 2,3-epoxycyclohex-5-en-1,4-diol (ECH), this metabolite against the Gram-positive bacterium, and a 2,6-dihydroxy-4-methylbenzoate (DMB) unit. Staphylococcus aureus (ATCC 6538) with IC50 and Compound (15) showed an inhibitory effect on HIV-1 MIC values of 21.8 and 97.3 lM, respectively (the replication in C8166 cells, with an EC50 value of 6.9 positive control ampicillin showed IC50 and MIC lM (the positive control indinavir sulfate showed an values of 1.2 and 3.9 lM) (Liu et al. 2008a). EC50 value of 8.81 nM) and also showed significant In other studies, Chloropestolide A (13) (Fig. 1) cytotoxicity against HeLa, MCF-7 and MDA-MB-231 was isolated from the same fungus. Chloropestolide A cell lines with IC50 values of 16.9, 15.5 and 15.9 lM, (13) showed significant inhibitory effects on the respectively (Liu et al. 2010). growth of HeLa and HT29 cancer cell lines with Liu and coworkers have used large scale P. fici re- GI50 values of 0.7 and 4.2 lM, respectively (Liu et al. fermentation to isolate minor fragments observed in 2009b). Chloropestolide B (14) (Fig. 1) was cytotoxic their previous work. Extending their work to isolate to three tested cell lines CNE1-LMP1, A375 and Chloropupukeananin (12) (Fig. 1), large-scale re- MCF-7 showing IC50 values of 16.4, 9.9, and fermenatation at 1 kg and subsequently at 3 kg on 23.6 lM, respectively while the positive control rice led to the isolation of Chloropupukeanolides C–D paclitaxel showed IC50 values of 4.2, 8.9, and (16, 17) (Fig. 1), a novel spiroketal skeleton. The 0.14 nM, respectively (Liu et al. 2013a). solution structure through-bond and spatial connec- Chloropupukeanolide A (15) (Fig. 1) was another tivities deduced using NMR were supported by the metabolite reported from P. fici. The structure was single crystal X-Ray diffraction data which aided in determined using homo and heteronuclear NMR unambiguous stereochemistry determinations at the techniques which established the presence of chiral centers.