Browsing by Author "Kate, A. S."

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Bioactive properties and metabolite profile of an endolichenic fungus, Hypoxylon lividipigmentum
(Faculty of Science, University of Kelaniya, Sri Lanka., 2021) Weerasinghe, W. R. H.; Shevkar, C. D.; Silva, R. S. De; Attanayake, R. N.; Weerakoon, G.; Kate, A. S.; Kalia, K.; Paranagama, P. A.
Endolichenic fungi (ELF) serve as a novel source of secondary metabolites. Hypoxylon lividipigmentum is an ELF isolated from the lichen Opegrapha medusulina, collected from mangrove plant Xylocarpus granatum from Negombo lagoon, Sri Lanka. The fungus was identified to the species level using morphological and DNA barcoding techniques. Ethyl acetate extract of the fungus was subjected to in vitro assays to determine antioxidant, anti-inflammatory, tyrosinase inhibitory and antibacterial potency. Liquid Chromatography-Mass Spectrometry (LCMS) dereplication was conducted on the crude extract in order to detect the secondary metabolites present. The extract reported a IC50 value of 18.34±1.37 µg/ml on par with the positive control BHT, in DPPH radical scavenging assay. It also exhibited moderate anti-inflammatory activity with an IC50 value of 81.08±1.05 μg/ml. Tyrosinase inhibitory activity was fairly comparable with an IC50 value of 121.20±2.55 μg/ml. Agar well diffusion assay was conducted to determine antibacterial activity against aerobic bacterial species Escherichia coli, Bacillus subtilis, Staphylococcus aureus and the anaerobic bacterial species Streptococcus mutans. Suppression of growth was shown only against B. subtilis. Five major mass peaks were observed during the study of LCMS profile of the extract. After a thorough dereplication process, two masses could be presumed to be from novel scaffolds. Since none of the mass peaks could be dereplicated within the species or genus level, it could be speculated that the chemical profile of Hypoxylon lividipigmentum was previously poorly explored in literature thus making it an interesting organism to study further for novel metabolites.
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.
Bioprospecting of an Endolichenic Fungus Phanerochaete sordida Isolated from Mangrove-Associated Lichen Bactrospora myriadea
(Journal of Chemistry, 2022) Weerasinghe, R. H.; Shevkar, C. D.,; Maduranga, K.; Pandey, K. H.; Attanayake, R. N.; Kate, A. S.; Weerakoon, G.; Behera, S. K.; Kalia, K. S.; Paranagama, P. A.
Bioassay-guided fractionation of the ethyl acetate extract of Phanerochaete sordida, an endolichenic fungus (ELF) isolated from the host lichen Bactrospora myriadea, collected from Negombo lagoon, Sri Lanka, led to the isolation of a bioactive compound. Following the identification of the fungus using morphological and DNA barcoding techniques, the pure compound was isolated using column chromatography, preparative TLC, and semipreparative HPLC. The structure elucidation was carried out using IR, HR-ESI-MS and 1H, 13C & 2D NMR spectroscopic methods. The in vitro bioassays conducted revealed that compound 1 has a high antioxidant activity with ABTS•+ (IC5058:91 ± 1:35 μM), moderate anti-inflammatory activity (IC50254:79 ± 1:41 μM), comparable antibacterial activity against the oral-bacterial strain Streptococcus mutans (MIC 898.79 μM and MLC 1797.58μM), moderate tyrosinase inhibition (IC501713:69 ± 8:65 μM), and moderate cytotoxicity against oral cancer (IC5013:65 ± 0:02 μM), in comparison with respective positive controls. The in silico experiments conducted for tyrosinase inhibition and cytotoxicity using Schrödinger revealed results in line with the in vitro results, thus confirming the bioactivities. The molecule also satisfies the key features of drug likeliness according to pharmacokinetic studies.
Bioprospecting of an Endolichenic Fungus Phanerochaete sordida Isolated from Mangrove-Associated Lichen Bactrospora myriadea
(Journal of Chemistry,, 2022) Weerasinghe, R. H.; Shevkar, C. D.; Maduranga, K.; Pandey, K. H.; Attanayake, R. N.; Kate, A. S.; Weerakoon, G.; Behera, S. K.; Kalia, K. S.; Paranagama, P. A.
Bioassay-guided fractionation of the ethyl acetate extract of Phanerochaete sordida, an endolichenic fungus (ELF) isolated from the host lichen Bactrospora myriadea, collected from Negombo lagoon, Sri Lanka, led to the isolation of a bioactive compound. Following the identification of the fungus using morphological and DNA barcoding techniques, the pure compound was isolated using column chromatography, preparative TLC, and semipreparative HPLC. The structure elucidation was carried out using IR, HR-ESI-MS and 1H, 13C & 2D NMR spectroscopic methods. The in vitro bioassays conducted revealed that compound 1 has a high antioxidant activity with ABTS•+ (IC5058:91 ± 1:35 μM), moderate anti-inflammatory activity (IC50254:79 ± 1:41 μM), comparable antibacterial activity against the oral-bacterial strain Streptococcus mutans (MIC 898.79 μM and MLC 1797.58μM), moderate tyrosinase inhibition (IC501713:69 ± 8:65 μM), and moderate cytotoxicity against oral cancer (IC5013:65 ± 0:02 μM), in comparison with respective positive controls. The in silico experiments conducted for tyrosinase inhibition and cytotoxicity using Schrödinger revealed results in line with the in vitro results, thus confirming the bioactivities. The molecule also satisfies the key features of drug likeliness according to pharmacokinetic studies.
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.