Publications by authors named "Rohitesh Kumar"

14 Publications

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Comparison of Chemical Composition and Biological Activities of Eight Species.

Pharmaceuticals (Basel) 2020 Dec 26;14(1). Epub 2020 Dec 26.

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic.

P. Beauv. is a group of vascular plants in the family Selaginellaceae Willk., found worldwide and numbering more than 700 species, with some used as foods and medicines. The aim of this paper was to compare methanolic (MeOH) and dichloromethane (DCM) extracts of eight species on the basis of their composition and biological activities. Six of these species are underinvestigated. Using ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis, we identified a total of 193 compounds among the tested species, with flavonoids predominating. MeOH extracts recovered more constituents that were detected, including selaginellins, the occurrence of which is only typical for this plant genus. Of all the tested species, contained the highest number of identified selaginellins. The majority of the compounds were identified in , the fewest compounds in . All the tested species demonstrated antioxidant activity using oxygen radical absorption capacity (ORAC) assay, which showed that MeOH extracts had higher antioxidant capacity, with the half maximal effective concentration (EC) ranging from 12 ± 1 ( ) to 124 ± 2 ( ) mg/L. The antioxidant capacity was presumed to be correlated with the content of flavonoids, (neo)lignans, and selaginellins. Inhibition of acetylcholinesterase (AChE) was mostly discerned in DCM extracts and was only exhibited in , , , and extracts with the half maximal inhibitory concentration (IC) in the range of 19 ± 3 to 62 ± 1 mg/L. Substantial cytotoxicity against cancer cell lines was demonstrated by the MeOH extract of , where the ratio of the IC HEK (human embryonic kidney) to IC HepG2 (hepatocellular carcinoma) was 7.9 ± 0.2. MeOH extracts inhibited the production of nitrate oxide and cytokines in a dose-dependent manner. Notably, halved the production of NO, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 at the following concentrations: 105 ± 9, 11 ± 1, and 10 ± 1 mg/L, respectively. Our data confirmed that extracts from species exhibited cytotoxicity against cancer cell lines and AChE inhibition. The activity observed in was the most promising and is worth further exploration.
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http://dx.doi.org/10.3390/ph14010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823444PMC
December 2020

Temperature-Responsive Pyraclostrobin-Loaded Octadecane Submicrocapsules with Lowered Toxicity.

Nanomaterials (Basel) 2020 Nov 28;10(12). Epub 2020 Nov 28.

Department of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic.

Pyraclostrobin (Pyr) is one of the most effective fungicides. However, it can degrade via photolysis in water, it is toxic to aquatic life and if inhaled, it has a low solubility in water, that leads to difficulties when applying to plants by spraying. Additionally, the necessity of repeated (weekly) sprays of fungicides when the pathogen growth risk is the highest, such as at the temperature range of 24 to 36 °C and increased humidity of about 95%, leads to loss of efficiency of the fungicide and overdose of chemicals. In the present study, pyraclostrobin was microencapsulated to solve the abovementioned issues. As a core of capsules octadecane (OD) with a melting point of 28 °C was used, thus, the release of pyraclostrobin was controlled via temperature change. Pyraclostrobin-loaded submicrocapsules (PyrSMCs) were characterized using SEM, DLS, TGA/DSC, HPLC, FTIR methods; stimuli-responsivity was tested employing in vitro tests with pathogenic culture (Fungal strain of - CPPF-453) grown in Petri dishes. Toxicity of PyrSMCs to was studied as well. Size of capsules was 200-600 nm along with the presence of bigger capsules with a diameter of 1-4 µm. PyrSMCs showed excellent antifungal effects above the melting point of octadecane. PyrSMCs demonstrated 29 times less toxicity than pyraclostrobin of technical grade. Overall, results show the potential of such capsules to be applied in the agricultural industry for precise agriculture strategies.
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http://dx.doi.org/10.3390/nano10122374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760801PMC
November 2020

Antimicrobial Activity of Extracts of Two Native Fruits of Chile: Arrayan () and Peumo ().

Antibiotics (Basel) 2020 Jul 25;9(8). Epub 2020 Jul 25.

Regional Center for Studies in Healthy Food (CREAS), CONICYT-Regional GORE Valparaíso Project R17A10001, Avenida Universidad, Valparaíso 2340000, Chile.

Arrayan and peumo fruits are commonly used in the traditional medicine of Chile. In this study, the concentration of the extracts halving the bacterial viability and biofilms formation and disruption of the drug-sensitive and drug-resistant strains of and was determined. The chemical composition of extracts was analyzed by high-resolution liquid chromatography coupled with mass spectrometry (U-HPLC/MS). The arrayan extract (Inhibitory concentration IC 0.35 ± 0.01 mg/mL) was more effective than peumo extract (IC 0.53 ± 0.02 mg/mL) in the inhibition of planktonic cells. Similarly, the arrayan extract was more effective in inhibiting the adhesion ( IC 0.23 ± 0.02 mg/mL, IC 0.29 ± 0.02 mg/mL) than peumo extracts ( IC 0.47 ± 0.03 mg/mL, IC 0.35 ± 0.01 mg/mL). Both extracts inhibited quorum sensing in a concentration-dependent manner, and the most significant was the autoinducer-2 type communication inhibition by arrayan extract. Both extracts also disrupted preformed biofilm of (arrayan IC 0.56 ± 0.04 mg/mL, peumo IC 0.59 ± 0.04 mg/mL). However, neither arrayan nor peumo extracts disrupted mature biofilm. U-HPLC/MS showed that both fruit extracts mainly possessed quercetin compounds; the peumo fruit extract also contained phenolic acids and phenylpropanoids. Our results suggested that both extracts could be used as natural antimicrobials for some skin and nosocomial infections.
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http://dx.doi.org/10.3390/antibiotics9080444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459669PMC
July 2020

Synthesis of a Unique Psammaplysin F Library and Functional Evaluation in Prostate Cancer Cells by Multiparametric Quantitative Single Cell Imaging.

J Nat Prod 2020 08 21;83(8):2357-2366. Epub 2020 Jul 21.

Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, Australia.

The spirooxepinisoxazoline alkaloid psammaplysin F () was selected as a scaffold for the generation of a unique screening library for both drug discovery and chemical biology research. Large-scale extraction and isolation chemistry was performed on a marine sponge ( sp.) collected from the Great Barrier Reef in order to acquire >200 mg of the desired bromotyrosine-derived alkaloidal scaffold. Parallel solution-phase semisynthesis was employed to generate a series of psammaplysin-based urea (-) and amide analogues (-) in low to moderate yields. The chemical structures of all analogues were characterized using NMR and MS data. The absolute configuration of psammaplysin F and all semisynthetic analogues was determined as 6, 7 by comparison of ECD data with literature values. All compounds (-) were evaluated for their effect on cell cycle distribution and changes to cancer metabolism in LNCaP prostate cancer cells using a multiparametric quantitative single-cell imaging approach. These investigations identified that in LNCaP cells psammaplysin F and some urea analogues caused loss of mitochondrial membrane potential, fragmentation of the mitochondrial tubular network, chromosome misalignment, and cell cycle arrest in mitosis.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00121DOI Listing
August 2020

Microthecaline A, a Quinoline Serrulatane Alkaloid from the Roots of the Australian Desert Plant Eremophila microtheca.

J Nat Prod 2018 04 13;81(4):1079-1083. Epub 2018 Mar 13.

Griffith Institute for Drug Discovery, Griffith University , Brisbane , QLD 4111 , Australia.

Chemical investigation of the roots of the Australian desert plant Eremophila microtheca yielded microthecaline A (1), a novel quinoline-serrulatane natural product. The structure of 1 was determined by spectroscopic analysis, and the absolute configuration was assigned by ECD. Compound 1 exhibited moderate antimalarial activity against Plasmodium falciparum (3D7 strain), with an IC of 7.7 μM. Microthecaline A represents the first quinoline-serrulatane alkaloid to be isolated from Nature.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00992DOI Listing
April 2018

Synthesis of antimalarial amide analogues based on the plant serrulatane diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid.

Bioorg Med Chem Lett 2017 09 15;27(17):4091-4095. Epub 2017 Jul 15.

Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia. Electronic address:

A plant-derived natural product scaffold, 3,7,8-trihydroxyserrulat-14-en-19-oic acid (1) was isolated in high yield from the aerial parts of the endemic Australian desert plant Eremophila microtheca. This scaffold (1) was subsequently used in the generation of a series of new amide analogues via a one-pot mixed anhydride amidation using pivaloyl chloride. The structures of all analogues were characterized using MS, NMR, and UV data. The major serrulatane natural products (1-3), isolated from the plant extract, and all amide analogues (6-15) together with several pivaloylated derivatives of 3,7,8-trihydroxyserrulat-14-en-19-oic acid (16-18) were evaluated for their antimalarial activity against 3D7 (chloroquine sensitive) and Dd2 (chloroquine resistant) Plasmodium falciparum strains, and preliminary cytotoxicity data were also acquired using the human embryonic kidney cell line HEK293. The natural product scaffold (1) did not display any antimalarial activity at 10µM. Replacing the carboxylic acid of 1 with various amides resulted in moderate activity against the P. falciparum 3D7 strain with IC values ranging from 1.25 to 5.65µM.
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http://dx.doi.org/10.1016/j.bmcl.2017.07.039DOI Listing
September 2017

Semi-synthesis and NMR spectral assignments of flavonoid and chalcone derivatives.

Magn Reson Chem 2016 Nov 25;54(11):880-886. Epub 2016 Jul 25.

Eskitis Institute for Drug Discovery, Griffith University, Brisbane, 4111, QLD, Australia.

Previous investigations of the aerial parts of the Australian plant Eremophila microtheca and Syzygium tierneyanum resulted in the isolation of the antimicrobial flavonoid jaceosidin (4) and 2',6'-dihydroxy-4'-methoxy-3',5'-dimethyl chalcone (7), respectively. In this current study, compounds 4 and 7 were derivatized by acetylation, pivaloylation, and methylation reactions. The final products, 5,7,4'-triacetoxy jaceosidin (10), 5,7,4'-tripivaloyloxy jaceosidin (11), 5,7,4'-trimethoxy jaceosidin (12), 2',6'-diacetoxy-4'-methoxy-3',5'-dimethyl chalcone (13), 2'-hydroxy-4'-methoxy-6'-pivaloyloxy-3',5'-dimethyl chalcone (14), and 2'-hydroxy-4',6'-dimethoxy-3',5'-dimethyl chalcone (15) were all fully characterized by NMR and MS. Derivatives 10 and 13 have been previously reported but were only partially characterized. This is the first reported synthesis of 11 and 14. The natural products and their derivatives were evaluated for their antibacterial and antifungal properties, and the natural product, jaceosidin (4) and the acetylated derivative, 5,7,4'-triacetoxy jaceosidin (10), showed modest antibacterial activity (32-128 µg/ml) against Staphylococcus aureus strains. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/mrc.4482DOI Listing
November 2016

Antibacterial and antifungal screening of natural products sourced from Australian fungi and characterisation of pestalactams D-F.

Phytochemistry 2016 Apr 29;124:79-85. Epub 2015 Dec 29.

Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia. Electronic address:

Eighteen natural products sourced from Australian micro- or macro-fungi were screened for antibacterial and antifungal activity. This focused library was comprised of caprolactams, polyamines, quinones, and polyketides, with additional large-scale isolation studies undertaken in order to resupply previously identified compounds. Chemical investigations of the re-fermented culture from the endophytic fungus Pestalotiopsis sp. yielded three caprolactam analogues, pestalactams D-F, along with larger quantities of the known metabolite pestalactam A, which was methylated using diazomethane to yield 4-O-methylpestalactam A. The chemical structures of the previously undescribed fungal metabolites were determined by analysis of 1D/2D NMR and MS data. The structure of 4-O-methylpestalactam A was confirmed following single crystal X-ray diffraction analysis. The antibacterial and antifungal activity of all compounds was assessed, which identified three compounds, (1S,3R)-austrocortirubin, (1S,3S)-austrocortirubin, and 1-deoxyaustrocortirubin with mild activity (100 μM) against Gram-positive isolates and one compound, 2-hydroxy-6-methyl-8-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, with activity against Cryptococcus neoformans and Cryptococcus gattii at 50 μM.
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http://dx.doi.org/10.1016/j.phytochem.2015.12.014DOI Listing
April 2016

The use of isolated natural products as scaffolds for the generation of chemically diverse screening libraries for drug discovery.

Nat Prod Rep 2016 Mar 7;33(3):372-81. Epub 2016 Jan 7.

Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.

A diverse range of strategies leading to natural product derived or inspired screening libraries aims to increase the number of new chemical entities emerging per year. However, the use of isolated natural products as scaffolds for the semi-synthesis of larger biological screening libraries remains rare. This particular method avoids the time-consuming and resource intensive de novo synthetic strategy for scaffold production, and has become more feasible through improvements to synthetic and isolation methodologies. This Highlight examines the increasing popularity of small- to large-sized screening libraries generated directly from isolated natural products. Several of the examples detailed herein show how this strategy can lead to improvements in not only potency but also other important (and often forgotten) drug discovery parameters such as toxicity, selectivity, lipophilicity and bioavailability. However, there are still improvements to be made to this method, particularly in the choice of the natural product scaffold and the derivatising reagents used. Avoidance of known nuisance compounds or structural alert motifs (e.g. PAINS) that interfere with bioactivity screens, and impact downstream drug development will play a significant role in the future success of this methodology. Incorporation of rational design strategies that take into account the physicochemical parameters (e.g. log P, MW, HBA, HBD) of the final semi-synthetic library analogues will also facilitate the discovery and development of leads and drugs. A multi-pronged approach to drug discovery that incorporates the use of isolated natural product scaffolds for library generation will surely be beneficial.
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http://dx.doi.org/10.1039/c5np00121hDOI Listing
March 2016

Design and Synthesis of a Screening Library Using the Natural Product Scaffold 3-Chloro-4-hydroxyphenylacetic Acid.

J Nat Prod 2015 Apr 24;78(4):914-8. Epub 2015 Mar 24.

†Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.

The fungal metabolite 3-chloro-4-hydroxyphenylacetic acid (1) was utilized in the generation of a unique drug-like screening library using parallel solution-phase synthesis. A 20-membered amide library (3-22) was generated by first converting 1 to methyl (3-chloro-4-hydroxyphenyl)acetate (2), then reacting this scaffold with a diverse series of primary amines via a solvent-free aminolysis procedure. The structures of the synthetic analogues (3-22) were elucidated by spectroscopic data analysis. The structures of compounds 8, 12, and 22 were confirmed by single X-ray crystallographic analysis. All compounds were evaluated for cytotoxicity against a human prostate cancer cell line (LNCaP) and for antiparasitic activity toward Trypanosoma brucei brucei and Plasmodium falciparum and showed no significant activity at 10 μM. The library was also tested for effects on the lipid content of LNCaP and PC-3 prostate cancer cells, and it was demonstrated that the fluorobenzyl analogues (12-14) significantly reduced cellular phospholipid and neutral lipid levels.
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http://dx.doi.org/10.1021/np500856uDOI Listing
April 2015

Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp.

Asian Pac J Trop Biomed 2013 Apr;3(4):291-6

Centre for Drug Discovery and Conservation, Institute of Applied Sciences, The University of the South Pacific, Laucala Campus, Suva, Fiji Islands.

Objective: To Isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus Penicillium sp. FF001 and to elucidate its structure.

Methods: The fungal strain FF001 with an interesting bioactivity profile was isolated from a marine Fijian sponge Melophlus sp. Based on conidiophores aggregation, conidia development and mycelia morphological characteristics, the isolate FF001 was classically identified as a Penicillium sp. The bioactive compound was identified using various spectral analysis of UV, high resolution electrospray ionization mass spectra, 1H and 13C NMR spectral data. Further minimum inhibitory concentrations (MICs) assay and brine shrimp cytotoxicity assay were also carried out to evaluate the biological properties of the purified compound.

Results: Bioassay guided fractionation of the EtOAc extract of a static culture of this Penicillium sp. by different chromatographic methods led the isolation of an antibacterial, anticryptococcal and cytotoxic active compound, which was identified as citrinin (1). Further, citrinin (1) is reported for its potent antibacterial activity against methicillin-resistant Staphylococcus aureus (S. aureus), rifampicin-resistant S. aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium showed MICs of 3.90, 0.97, 1.95 and 7.81 µg/mL, respectively. Further citrinin (1) displayed significant activity against the pathogenic yeast Cryptococcus neoformans (MIC 3.90 µg/mL), and exhibited cytotoxicity against brine shrimp larvae LD50 of 96 µg/mL.

Conclusions: Citrinin (1) is reported from sponge associated Penicillium sp. from this study and for its strong antibacterial activity against multi-drug resistant human pathogens including cytotoxicity against brine shrimp larvae, which indicated that sponge associated Penicillium spp. are promising sources of natural bioactive metabolites.
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http://dx.doi.org/10.1016/S2221-1691(13)60065-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634926PMC
April 2013

Investigations of the marine flora and fauna of the Fiji Islands.

Nat Prod Rep 2012 Dec 14;29(12):1424-62. Epub 2012 Sep 14.

Centre for Drug Discovery and Conservation, Institute of Applied Sciences, The University of the South Pacific, Suva, Fiji.

Over the past 30 years, approximately 140 papers have been published on marine natural products chemistry and related research from the Fiji Islands. These came about from studies starting in the early 1980s by the research groups of Crews at the University of California Santa Cruz, Ireland at the University of Utah, Gerwick from the Scripps Institution of Oceanography, the University of California at San Diego and the more recent groups of Hay at the Georgia Institute of Technology (GIT) and Jaspars from the University of Aberdeen. This review covers both known and novel marine-derived natural products and their biological activities. The marine organisms reviewed include invertebrates, plants and microorganisms, highlighting the vast structural diversity of compounds isolated from these organisms. Increasingly during this period, natural products chemists at the University of the South Pacific have been partners in this research, leading in 2006 to the development of a Centre for Drug Discovery and Conservation (CDDC).
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http://dx.doi.org/10.1039/c2np20055dDOI Listing
December 2012

Three bioactive sesquiterpene quinones from the Fijian marine sponge of the genus Hippospongia.

Nat Prod Res 2013 10;27(16):1488-91. Epub 2012 Sep 10.

a Centre for Drug Discovery and Conservation, Institute of Applied Sciences, The University of the South Pacific , Suva , Fiji Islands.

A sesquiterpenoid quinone, epi-ilimaquinone (1), and two sesquiterpene amino quinones, smenospongine (2) and glycinylilimaquinone (3), were isolated from the Fijian marine sponge Hippospongia sp. The structures of these compounds were determined by spectroscopic analysis. Compounds 1 and 3 were reported for the first time in this study from the sponge of the genus Hippospongia. Compound 1 displayed potent cytotoxic activity and showed antibacterial activity against methicillin-resistant Staphylococcus aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium and displayed antifungal activity against amphotericin-resistant Candida albicans while compounds 2 and 3 showed moderate cytotoxic activity. However, compound 1 did not show appreciable antifungal activity against wild type C. albicans, Cryptococcus neoformans, Aspergillus niger, Penicillium sp., Rhizopus sporangia or Sordaria sp.
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http://dx.doi.org/10.1080/14786419.2012.722086DOI Listing
March 2014

Aurantoside K, a new antifungal tetramic acid glycoside from a Fijian marine sponge of the genus Melophlus.

Mar Drugs 2012 Jan 18;10(1):200-8. Epub 2012 Jan 18.

Centre for Drug Discovery and Conservation, Institute of Applied Sciences, The University of the South Pacific, Suva, Fiji Islands.

A new tetramic acid glycoside, aurantoside K, was isolated from a marine sponge belonging to the genus Melophlus. The structure of the compound was elucidated on the basis of spectroscopic analysis (¹H NMR, ¹H-¹H COSY, HSQC, and HMBC, as well as high-resolution ESILCMS). Aurantoside K did not show any significant activity in antimalarial, antibacterial, or HCT-116 cytotoxicity assays, but exhibited a wide spectrum of antifungal activity against wild type Candida albicans, amphotericin-resistant C. albicans, Cryptococcus neoformans, Aspergillus niger, Penicillium sp., Rhizopus sporangia and Sordaria sp.
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http://dx.doi.org/10.3390/md10010200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280539PMC
January 2012
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