Niranjan Parajuli | Tribhuvan University (original) (raw)

Papers by Niranjan Parajuli

Research in Microbiology, Jun 1, 2005

We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucet... more We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucetius ATCC 27952. AfsR-p shares 60% sequence identity with AfsR from Streptomyces coelicolor A3 (2). afsR-p was expressed under the control of the ermE * promoter in its hosts S. peucetius, Streptomyces lividans TK 24, Streptomyces clavuligerus and Streptomyces griseus. We observed overproduction of doxorubicin (4-fold) in S. peucetius, γ-actinorhodin (2.6-fold) in S. lividans, clavulanic acid (1.5-fold) in S. clavuligerus and streptomycin (slight) in S. griseus. Overproduction was due to expression of the gene in these strains as compared to the wild-type strains harboring the vector only. Comparative study of the expression of afsR-p revealed that regulatory networking in Streptomyces is not uniform. We speculate that phosphorylated AfsR-p becomes bound to the promoter region of afsS. The latter activates other regulatory genes, including pathway regulatory genes, and induces the production of secondary metabolites including antibiotics. We identified specific conserved amino acids and exploited them for the isolation of the partial sequence of the afsR homologue from S. clavuligerus and Streptomyces achromogens (rubradirin producer). Such findings provide additional evidence for the presence of a serine/threonine and tyrosine kinase-dependent global regulatory network in Streptomyces.

Biomass Conversion and Biorefinery, May 13, 2023

In the 3 rd sentence of the Abstract, the line reads: The biomass recovery was found highest unde... more In the 3 rd sentence of the Abstract, the line reads: The biomass recovery was found highest under the liquid hot water (autoclave; 9.477 ± 0.017%) pretreatment conditions. Here, this result is a typo error. It should be '94.77± 0.017%' instead of 9.477 ± 0.017%. The original article has been corrected. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Analytical Biochemistry, Dec 1, 2011

BMC Research Notes, Nov 8, 2019

Objectives: The study was carried out to optimize the phenotypic method to characterize the sickl... more Objectives: The study was carried out to optimize the phenotypic method to characterize the sickle cell trait (SCT), sickle cell anemia (SCA), and β-thalassemia (β-TT) suspected sample from tharu community of South Western province-5, Nepal. SCT and SCA were further evaluated by genotypic method employing amplification refractory mutation system (ARMS PCR). Moreover, Glucose 6 phosphate dehydrogenase (G6PD) was estimated in those hemoglobinopathy to observe its prevalence. The accurate and reliable method can play an important role in reduction of morbidity and mortality rate. Results: The 100 suspected cases were subjected to phenotypic method adopting cellulose acetate electrophoresis and genotypic method using ARMS PCR which portraits (5%) SCA positive test showing HBS/HBS, (38%) SCT positive trait HBA/HBS and (36%) cases normal HBA/HBA. β-TT (21%) cases were confirmed by electropherogram. G6PD deficiency was observed in (40%) of SCA, (18.4%) of SCT, (4.8%) of β-TT and (2.8%) in normal cases. Increased G6PD were developed only in SCT (5.3%) and β-TT (4.8%). The study highlighted sickle cell disorder (SCD) and β-TT as the most common hemoglobinopathy coexisting with G6PD deficiency. Though hemoglobinopathy sometime could be protective in malaria but G6PD deficiency can cause massive hemolysis which may exacerbate the condition.

Phytotherapy Research, Oct 9, 2020

The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acut... more The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective.

Metabolic enzymes are often targeted for drug development programs of metabolic diseases such as ... more Metabolic enzymes are often targeted for drug development programs of metabolic diseases such as diabetes and its complications. Many secondary metabolites isolated from natural products have shown therapeutic action against these enzymes. However, some commercially available synthetic drugs have shown unfriendly impacts with various side effects. Thus, this research has focused on a comprehensive study of secondary metabolites showing better inhibitory activities towards metabolic enzymes such as α-amylase, α-glucosidase, aldose reductase, and lipase. Further receptor-based virtual screening was performed against the various secondary metabolites database designed in-silico. Using Gold combined with subsequent post-docking analyses, the score was obtained as methyl xestospongic ester (Gold score 65.83), 2,″4″-O-diacetylquercitrin (Gold score 65.15), kaempferol-3-O-neohesperidoside (Gold score 53.37) and isosalvianolic acid C methyl ester (Gold score 53.44) for lipase, aldol reductase, α-amylase, and α-glucosidase, respectively. Besides, vitexin and isovitexin for α-amylase; N-trans-Caffeoyl-tyramin for α-glucosidase; purpurolide F and schaftoside for lipase; acteoside and orientin for aldose reductase could be potential drugs for respective enzymes based on in-silico analyses, supported by experimental IC50 values reported. They could bind to the competitive sites of the various targets of metabolic enzymes, and finally, toxicity analysis using ProTox-II was also performed.

Journal of Chemistry, Jul 9, 2022

Medicinal plants have been used from the beginning of human civilization against various health c... more Medicinal plants have been used from the beginning of human civilization against various health complications. Dengue virus (DENV) has emerged as one of the most widespread viruses in tropical and subtropical countries. Yet no clinically approved antiviral drug is available to combat DENV infection. Consequently, the search for novel antidengue agents from medicinal plants has assumed more insistence than in previous days. is study has focused on 31 potential antidengue molecules from secondary metabolites to examine their inhibitory activity against DENV nonstructural proteins through molecular docking and pharmacokinetics studies. In this research, the wet lab experiments were tested on a computational platform. Agathis avone and pectolinarin are the top-scored inhibitors of DENV NS2B/NS3 protease and NS5 polymerase, respectively. Epigallocatechin gallate, Pinostrobin, Panduratin A, and Pectolinarin could be potential lead compounds against NS2B/NS3 protease, while acacetin-7-O-rutinoside against NS5 polymerase. Moreover, agathis avone (LD 50 1430 mg/kg) and pectolinarin (LD 50 5000 mg/kg) exhibited less toxicity than nel navir (LD 50 600 mg/kg) and balapiravir (LD 50 824 mg/kg), and the reference drugs. Further research on clinical trials is required to analyze the therapeutic e cacy of these metabolites to develop new potential drug candidates against di erent serotypes of DENV.

Molecules, Nov 4, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Journal of Nanomaterials, Feb 5, 2021

Over the past couple of decades, nanomaterials have advanced the research in materials; biomedica... more Over the past couple of decades, nanomaterials have advanced the research in materials; biomedical, biological, and chemical sciences; etc., owing to their peculiar properties at the nanoregime compared to their bulk composition. Applications of nanoparticles in the fields like medicine and agriculture have been boosted due to the development of different methodologies developed to synthesize specific shapes and sizes. Silver nanoparticles have tunable physical and chemical properties, so it has been studied widely to improve its applicability. The antimicrobial properties of Ag NPs are finding their application in enhancing the activity of drugs (like Amphotericin B, Nystatin, Fluconazole) and composite scaffolds for controlled release of drugs and targeted delivery of drugs due to their low toxicity and biocompatibility. Similarly, their surface plasmon resonance property makes Ag NPs a top-notch material for developing (bio)sensors, for instance, in surface-enhanced Raman spectroscopy, for detecting biomarkers, diseases, pollutants, and higher catalytic activity in photochemical reactions. Besides these, highly conducting Ag NPs are used in wearable and flexible sensors to generate electrocardiographs. Physicochemical or biological approaches are used to prepare Ag NPs; however, each method has its pros and cons. The prohibitive cost and use of hazardous chemicals hinder the application of physicochemical synthesis. Likewise, biological synthesis is not always reproducible for extensive use but can be a suitable candidate for therapeutic activities like cancer therapy. Excess use of Ag NPs is cytotoxic, and their unregulated discharge in the environment may have effects on both aquatic and terrestrial biota. The research in Ag NPs has always been driven by the need to develop a technology with potential benefits and minimal risk to environmental and human health. In this review, we have attempted to provide an insight into the application of Ag NPs in various sectors along with the recent synthetic and characterization techniques used for Ag NPs.

The COVID-19 pandemic has affected higher education institutions (HEIs) worldwide and reshaped th... more The COVID-19 pandemic has affected higher education institutions (HEIs) worldwide and reshaped the existing educational system. Due to travel constraints and physical separation, there has been a global shift toward distance learning, and Nepal is no exception. This research intends to assess the practicality of online education by evaluating learners' experiences amidst COVID-19. A cross-sectional study was directed among HEIs students in Nepal using selfstructured questionnaires. Our study revealed that 64.6% of the respondents were unsatisfied with online classes. More than half of the respondents (53.4%) use cell phones for online studies. Online education was reported to be unappealing to 28.8% of respondents. Variables such as age group (p = 0.05), enjoying class (p < 0.001), hours spent for an online class in a day (p = 0.05), and period for educational work using an electronic device (p = 0.1) were found significant with satisfaction level using both bivariate test and inferential test of univariate binary logistics regression. The challenges and opportunities encountered among students and faculties are highlighted along with the recommendations for fortifying communication in online-based teaching/learning.

Advanced Science, Engineering and Medicine, Mar 1, 2017

Nanotechnology is one of the best tools of this decisive period where antibiotics lose their cred... more Nanotechnology is one of the best tools of this decisive period where antibiotics lose their credibility against several bacterial and fungal species. This technology is used for a long time, it is not a new technology and the use of this nanotechnology is increasing day by day, and more and more advance techniques are introduced for the synthesis of these nanoparticles till today. Every new method showed control over the previous one, where some methods used high temperature and some showed high usage of pressure and other toxic chemicals. Nowadays, nanotechnology is mostly used in terms of green synthesis. The green synthesis process for the preparation of nanoparticle is time saving and economical and eco-friendly. Besides this, no harmful chemicals are used in this process like used in other techniques; only phytohormones are being used in the preparation. The nanoparticles synthesized using silver nitrate and the leaves of Catharanthus roseus showed high rate of efficacy against selected strains of bacteria. These silver nitrate-containing NPs showed different zones of inhibitions against selected microorganisms. C. roseus is a plant that is mostly used in traditional medicines. These NPs showed high zones of inhibition against Shigella dysenteriae, Klebsiella pneumoniae, Bacillus anthraces, Staphylococcus aureus, and Pseudomonas aeruginosa.

Biotechnology and Bioprocess Engineering, Apr 1, 2006

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RSC Advances, 2021

Unnatural amino acids have gained significant attention in protein engineering and drug discovery... more Unnatural amino acids have gained significant attention in protein engineering and drug discovery as they allow the evolution of proteins with enhanced stability and activity. The incorporation of unnatural amino acids into proteins offers a rational approach to engineer enzymes for designing efficient biocatalysts that exhibit versatile physicochemical properties and biological functions. This review highlights the biological and synthetic routes of unnatural amino acids to yield a modified protein with altered functionality and their incorporation methods. Unnatural amino acids offer a wide array of applications such as antibody-drug conjugates, probes for change in protein conformation and structure-activity relationships, peptide-based imaging, antimicrobial activities, etc. Besides their emerging applications in fundamental and applied science, systemic research is necessary to explore unnatural amino acids with novel side chains that can address the limitations of natural amino acids.

BMC complementary medicine and therapies, 2021

Background: Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwid... more Background: Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generate atherosclerosis and cholesterol crystals. β-Hydroxy β-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced cholesterol levels, most of them have failed to meet potential drug candidates' requirements. Here, we have carried out an in-silico analysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR in a wet lab setup. Methods: Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were selected based on the IC 50 values reported in in vitro assays. Further, receptor-based virtual screening was carried out against secondary metabolites using GOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-silico ADMET analysis was carried out to explore their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. Results: The molecular docking of amentoflavone (GOLD score 70.54, ΔG calc. = − 10.4 Kcal/mol) and ganomycin I (GOLD score 59.61, ΔG calc. = − 6.8 Kcal/mol) displayed that the drug has effectively bound at the competitive site of XO and HMGR, respectively. Besides, 6-paradol and selgin could be potential drug candidates inhibiting XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl (6′ → 1″)-O-α-D-glucopyranoside could be potential drug candidates to maintain serum cholesterol. In-silico ADMET analysis has shown that these sixteen metabolites were optimal within the categorical range compared to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through ProTox-II revealed that 6-gingerol, ganoleucoin K, and ganoleucoin Z are toxic for human use. Conclusion: This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.

Proceedings of the National Academy of Sciences of the United States of America, Jun 17, 2008

Journal of Chemistry, Jul 13, 2023

Aldose reductase has received extensive research as a key enzyme in the development of long-term ... more Aldose reductase has received extensive research as a key enzyme in the development of long-term problems linked to diabetes mellitus. Overexpression of this enzyme or with exceeded glucose concentration in the blood increases sorbitol on the retina leading to retinopathy, which is the adverse efect of type II diabetes. Approximately 100 million people are sufering from diabetic retinopathy globally. Tis research is focused on studying the total phenolic content (TPC), total favonoid content (TFC), antioxidant potential, and aldose reductase inhibiting properties of selected medicinal plants such as Anacyclus pyrethrum, Bergenia ciliata, Rhododendron arboreum, and Swertia chirayita. In addition, ADMET analysis and molecular docking of seven previously identifed compounds from the chosen medicinal plants were carried out against human aldose reductase (PDB ID: 4JIR). Te ethanol extract of S. chirayita exhibited the highest TPC (4.63 ± 0.16 mg GAE/g) and TFC (0.90 ± 0.06 mg QE/g). Analysis of 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based antioxidant assay showed that IC 50 of the ethanolic extract of B. cilata and R. arboreum showed a signifcant antioxidant activity with IC 50 value of 0.05 mg/mL. Te percentage inhibition of AR by extract of B. ciliata (94.74 ± 0.01%) was higher than other plant extracts. A molecular docking study showed that morin isolated from B. ciliata showed a good binding interaction with AR. Tis study showed that the extracts of A. pyrethrum, B. ciliata, and R. arboreum could be potential sources of inhibitors against AR to treat retinopathy.

Bibechana, Sep 12, 2022

Bergenia pacumbis, a perennial herb of the Saxifragaceae family, usually referred to as 'Pashanbh... more Bergenia pacumbis, a perennial herb of the Saxifragaceae family, usually referred to as 'Pashanbheda' is geographically distributed within the temperate Himalaya including Nepal. The purpose of this study was to evaluate the phytochemical analysis as well as in vitro antioxidant and antibacterial activities of methanolic rhizome extract of B. pacumbis. The rhizome of B. pacumbis was extracted in methanol using the Soxhlet apparatus and then the extract was concentrated. The rhizome extract was tested for phytochemicals using the standard protocol. The in vitro antioxidant activity of the extract was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl free radical scavenging assay. The 50 % inhibitory concentration (IC50) values of ascorbic acid and B. pacumbis were found to be 11.91 ± 0.03 μg/mL and 11.99 ± 0.05 μg/mL respectively that indicate B. pacumbis is a good source of antioxidant agents. The extract was further tested for antibacterial activity through the agar well diffusion method and found to be effective against Staphylococcus aureus (16 mm) and Klebsiella pneumoniae (12 mm). The present study validates the traditional use of B. pacumbis.

Sustainable Chemistry and Pharmacy, Jun 1, 2022

Journal of Nanomaterials, Aug 22, 2022

Lately, the upsurge in the liberation of synthetic dyes into the environment, primarily by the te... more Lately, the upsurge in the liberation of synthetic dyes into the environment, primarily by the textile industries, is a threat to the natural habitat and existing ecosystem. Various methods such as adsorption and degradation with nanoparticles are currently being used to degrade those hazardous materials, but still, the yearning for novel methods continues. In this study, hydrothermal reactions were performed at 160°C to synthesize manganese dioxide nanostructures (MnNSs) under different incubation periods that facilitated the comparison of the size, morphology, and crystallinity of MnNSs. The study revealed the change in crystallinity over the incubation period; MnNSs prepared at 24 hrs were highly crystalline among others. Additionally, the size and morphology of MnNSs changed from the sea-urchin or flower-like structure, predominantly sheet/ layer form, to nanorods as the reaction proceeded for 24 hrs. Characterization of MnNSs was followed by heterogeneous Fenton's reaction, using α-manganese dioxide nanostructures, for the degradation of methylene blue (MB). To further understand the catalytic activity of MnNSs, the synthesized nanostructures were subjected to degrade MB at varied time intervals, both with and without hydrogen peroxide (H 2 O 2). Catalytically, MnNSs evinced good potential for degrading MB dye in the presence of H 2 O 2 ; MnNSs prepared at 24 hrs degraded MB up to 73% within 110 minutes.

Pharmacognosy Research, Oct 18, 2021

Background: The increasing frequency of diabetes patients and the reported side effects of commer... more Background: The increasing frequency of diabetes patients and the reported side effects of commercially available anti-hyperglycemic drugs have gathered the attention of researchers towards the search for new therapeutic approaches. Inhibition of activities of carbohydrate hydrolyzing enzymes is one of the approaches to reduce postprandial hyperglycemia by delaying digestion and absorption of carbohydrates. Objectives: The objective of the study was to investigate phytochemicals, antioxidants, digestive enzymes inhibitory effect, and molecular docking of potent extract. Materials and Methods: In this study, we carry out the substratebased α-glucosidase and α-amylase inhibitory activity of Asparagus racemosus, Bergenia ciliata, Calotropis gigantea, Mimosa pudica, Phyllanthus emblica, and Solanum nigrum along with the determination of total phenolic and flavonoids contents. Likewise, the antioxidant activity was evaluated by measuring the scavenging of DPPH radical. Additionally, antibacterial activity was also studied by Agar well diffusion method. Molecular docking of bioactive compounds from B. ciliata was performed via AutoDock vina. Results: B. ciliata, M. pudica, and P. emblica exhibit significant inhibitory activity against the α-glucosidase and α-amylase with IC 50 (µg/ml) of (2.24 ± 0.01, 46.19 ± 1.06), (35.73 ± 0.65, 99.93 ± 0.9) and (8.12 ± 0.29, no significant activity) respectively indicating a good source for isolating a potential drug candidate for diabetes. These plant extracts also showed significant antioxidant activity with the IC 50 ranges from 13.2 to 26.5 µg/mL along with the significant antibacterial activity towards Staphylococcus aureus and Klebsiella pneumonia. Conclusion: Bergenia extract appeared to be a potent α-glucosidase and α-amylase inhibitor. Further research should be carried out to characterize inhibitor compounds.