Browsing by Author "Shevkar, C."

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Bioactive Properties and Metabolite Profiles of Endolichenic Fungi in Mangrove Ecosystem of Negombo Lagoon, Sri Lanka
(Natural Product Communications, 2022) Weerasinghe, R. H.; Maduranga, K.; Attanayake, R. N.; Shevkar, C.; Kate, A. S.; Weerakoon, G.; Kalia, K.; Paranagama, P.
Endolichenic fungi (ELF) serve as a novel source of natural products with distinctive bioactivities. A total of 58 ELF isolated from 29 lichens collected from mangrove and mangrove-associated plants of Negombo lagoon, Sri Lanka were identified using morphological and DNA barcoding techniques. Ethyl acetate extracts of 18 such identified ELF isolates were subjected to in vitro assays to determine antioxidant, anti-inflammatory, tyrosinase inhibitory and antibacterial potency. Liquid chromatography–mass spectrometry (LC–MS) dereplication was conducted on the crude extracts in order to detect the secondary metabolites present. The extracts of Daldinia eschscholtzii and Hypoxylon lividipigmentum had the highest radical scavenging activity with SC50 values 14.27 ±0.24 μg/mL and 18.34±1.37 μg/mL, respectively. D. eschscholtzii also exhibited remarkable anti-inflammatory activity (IC50 7.97 ±0.09 μg/mL). Tyrosinase inhibitory activity was highest in Cytospora xylocarpi (IC50 68.50 ±0.34 μg/mL), while the highest activity against aerobic bacterial species Escherichia coli, Bacillus subtilis, Staphylococcus aureus and the anaerobic bacterial strain Streptococcus mutans was observed in the extracts of Xylaria feegenesis and Curvularia lunata. After a thorough study of the LC–MS profiles, it was found that the chemical profiles of Neofusicoccum occulatum, H. lividipigmentum and Myramaececium rubricosum were previously poorly explored in the literature.
Chemical characterization of endolichenic fungi, Talaromyces pinophilus residing in the lichen, Arthonia sp. collected from mangroves of Sri Lanka
(Institute of Chemistry Ceylon Adamantane House, Rajagiriya, Sri Lanka., 2020) Shevkar, C.; Armarkar, A.; Maduranga, K.; Weerasinghe, R.; Pandey, K.; Kalia, K.; Paranagama, P. A.; Kate, A.
Lichens are one of the interesting symbiotic organisms comprising of algae, fungi and other microbiota. The complex miniature ecosystem of lichen provides a competitive environment to endolichenic fungi, which makes it suitable for the production of structurally diverse molecules. Mangroves of Sri Lanka are well-known for the presence of various type of lichens and hence, in this study, 32 specimens of lichen were collected from mangroves of Puttalam Lagoon of Sri Lanka. LCMS based dereplication study was carried out for the isolated 70 cultures of endolichenic fungi from lichens. Talaromin B and Ergochrome BB were present in the ethyl acetate extract of Talaromyces pinophilus along with probable novel compounds having m/z [M+H]+ 663.2321, 778.4128, 401.3029 with “no hit” in Dictionary of Natural Products (DNP). The mentioned extract showed promising anti-cancer activity having IC50 of 50.32 μg/mL tested against MCF-7 cell line (Human breast cancer cell line) by Alamar blue assay. The extract was then scaled up for further isolation of masses showing no hits in DNP. Here, 2 known and 2 new compounds were isolated with 95-98% purity from the scaled up fermentation batch including [NIPER20099_83_7/30_1] Peniazaphilin B and a macrocyclicpolyester [NIPER20099_83_7/30_2] (15G25α). Structural elucidation of two novel molecules is in process. All four molecules were tested in vitro against MCF-7 cell line and only one molecule [NIPER20099_83_7/30_3] having molecular weight 560.2045 showed promising activity with the IC50 value of 22.15μM. The study suggest Talaromyces pinophilus might serve as a source of novel cytotoxic hit. Investigating secondary metabolites of the endolichenic fungi might help us to unravel the complex ecosystems of lichen and help us understand its further therapeutic benefits.
Cytotoxic Bioxanthracene and Macrocyclic Polyester from Endolichenic Fungus Talaromyces pinophilus: In-Vitro and In-Silico Analysis
(Indian J Microbiol, 2022) Shevkar, C.; Armarkar, A.; Weerasinghe, R.; Maduranga, K.; Behera, S.K.; Kalia, Kiran; Paranagama, P.; Kate, A. S.; Pandey, K.
Lichens are used in folklore medicines across the globe for wound healing and to treat skin disorders and respiratory diseases. They are an intricate symbiosis between fungi and algae with the domination of fungal counterparts. Recent research studies pointed out that yeast is a third major partner in lichens. Endolichenic fungi (ELF) are also a part of this complex miniature ecosystem. The highly competitive environment of lichens compels ELF to produce toxic metabolites which are comparatively less explored for their chemical diversity and use. Here, we investigated 31 ELF isolated from 32 lichens found on mangrove plants at Puttalam Lagoon of Sri Lanka to find cytotoxic molecules by applying LC-UV-HRMS analysis and in vitro bioassays. The studies resulted in the identification of three potent cytotoxic molecules from endolichenic fungi Talaromyces pinophilus isolated from host lichen Porina tetracerae. The ethyl acetate extract of this fungus showed moderate cytotoxicity against the breast cancer cell line. Chemical characterization of ethyl acetate extract of T. pinophilus produced peniazaphilin B, 152G256a-1, and ES-242-3. The structures of these molecules were confirmed by NMR and MS data. We are reporting ES-242-3 for the first time from the genus Talaromyces and peniazaphilin B and 152G256a-1 from T. pinophilus. The isolated compounds were evaluated for their anticancer potential against breast, oral and cervical cancer cell lines. Compound 152G256a-1 showed potent cytotoxicity against oral cancer (CAL-27 cell line) with an IC50 value of 2.96 ± 0.17 lM while ES-242-3 showed the best activity against breast cancer (MCF-7 cell line) and cervical cancer (HeLa cell line) with IC50 value 14.08 ± 0.2 lM and 4.46 ± 0.05 lM respectively. An insilico analysis was carried out to predict the mechanism of in-vitro activity, drug likeliness, and pharmacokinetic profile of the isolated compounds. The study confirms the potential of ELF T. pinophilus to produce diverse bioactive scaffolds and encourages the researchers to further explore the fungus and its metabolites with newer technologies to produce potent anticancer leads.
Exploration of Potent Cytotoxic Molecules from Fungi in Recent Past to Discover Plausible Anticancer Scaffolds
(Chemistry & Biodiversity, 2022) Shevkar, C.; Pradhan, P.; Armarkar, A.; Pandey, K.; Kalia, K.; Paranagama, P.; Kate, A. S.
Fungi are known to produce diverse scaffolds possessing unique biological activities, however, to date, no molecule discovered from a fungal source has reached the market as an anti-cancer drug. Every year number of cytotoxic molecules of fungal origin are getting published and critical analysis of those compounds is necessary to identify the potent ones. A review mentioning the best cytotoxic fungal metabolites and their status in the drug development was published in 2014. In this report, we have included 176 cytotoxic molecules isolated from fungi after 2014 and categorized them according to their potencies such as IC50 values below 1 μM, 1–5 μM, and 5–10 μM. The emphasis was given to those 42 molecules which have shown IC50 less than 1 μM and discussed to a great extent. This review shall provide potent scaffolds of fungal origin which can be given priority in the development as a drug candidate for cancer therapeutics.
Identification of Novel Bioactive Compounds, Neurosporalol 1 and 2 from an Endolichenic Fungus, Neurospora ugadawe Inhabited in the Lichen Host, Graphis tsunodae Zahlbr. from Mangrove Ecosystem in Puttalam Lagoon, Sri Lanka
(ASSIIAN JOURNAL OF CHEMIISSTRY, 2021) Maduranga, H.; Weerasinghe, W.; Attanayake, R.; Santhirasegaram, S.; Shevkar, C.; Kate, A.; Weerakoon, G.; Samanthi, K.; Kalia, K.; Paranagama, P. A.
Endolichenic fungi (ELF) have been recognized as a promising source of bioactive secondary metabolites. Sri Lanka, a biodiversity hotspot, harbours a remarkable diversity in mangrove ecosystems. In the present study, endolichenic fungi obtained from mangrove lichens of Puttalam lagoon were studied for their secondary metabolites. An endolichenic fungus, Neurospora ugadawe, isolated from the lichen host Graphis tsunodae Zahlbr. was identified up to the species level. Secondary metabolites of N. ugadawe were extracted into ethyl acetate and crude extract showed promising antioxidant and anti-inflammatory activities. Bioassay guided separation on silica gel column chromatography and preparative TLC were performed to isolate the bioactive pure compounds. Two novel bioactive pure compounds were identified as Neurosporalol 1 and Neurosporalol 2. Neurosporalol 1 showed the highest antioxidant activity compared with the positive control BHT. Further, this compound showed very low anti-inflammatory activity compared to that of the positive control aspirin. Neurosporalol 2 showed comparable antioxidant and moderate anti-inflammatory activities.
Identification of Novel Bioactive Compounds, Neurosporalol 1 and 2 from anEndolichenic Fungus, Neurospora ugadawe Inhabited in the Lichen Host,Graphis tsunodae Zahlbr. from Mangrove Ecosystem in Puttalam Lagoon, Sri Lanka
(Asian Journal of Chemistry, 2021) Maduranga, H.; Weerasinghe, W.; Attanayake, R.; Santhirasegaram, S.; Shevkar, C.; Kate, A.S.; Weerakoon, G.; Samanthi, K.; Kalia, K.; Paranagama, P. A.
Endolichenic fungi (ELF) have been recognized as a promising source of bioactive secondary metabolites. Sri Lanka, a biodiversity hotspot, harbours a remarkable diversity in mangrove ecosystems. In the present study, endolichenic fungi obtained from mangrove lichens of Puttalam lagoon were studied for their secondary metabolites. An endolichenic fungus, Neurospora ugadawe, isolated from the lichen host Graphis tsunodae Zahlbr. was identified up to the species level. Secondary metabolites of N. ugadawe were extracted into ethyl acetate and crude extract showed promising antioxidant and anti-inflammatory activities. Bioassay guided separation on silica gel column chromatography and preparative TLC were performed to isolate the bioactive pure compounds. Two novel bioactive pure compounds were identified as Neurosporalol 1 and Neurosporalol 2. Neurosporalol 1 showed the highest antioxidant activity compared with the positive control BHT. Further, this compound showed very low anti-inflammatory activity compared to that of the positive control aspirin. Neurosporalol 2 showed comparable antioxidant and moderate anti-inflammatory activities.