Utilization of Cassava Wastewater for Low-Cost Production of Prodigiosin via Serratia marcescens TNU01 Fermentation and Its Novel Potent α-Glucosidase Inhibitory Effect

The purpose of this study was to reuse cassava wastewater (CW) for scaled-up production, via the fermentation of prodigiosin (PG), and to conduct an evaluation of its bioactivities. PG was produced at the yield of high 6150 mg/L in a 14 L-bioreactor system, when the designed novel medium (7 L), containing CW and supplemented with 0.25% casein, 0.05% MgSO4, and 0.1% K2HPO4, was fermented with Serratia marcescens TNU01 at 28 °C in 8 h. The PG produced and purified in this study was assayed for some medical effects and showed moderate antioxidant, high anti-NO (anti-nitric oxide), and potential α-glucosidase inhibitory activities. Notably, PG was first reported as a novel effective α-glucosidase inhibitor with a low IC50 value of 0.0183 µg/mL. The commercial anti-diabetic drug acarbose was tested for comparison and had a lesser effect with a high IC50 value of 328.4 µg/mL, respectively. In a docking study, the cation form of PG (cation-PG) was found to bind to the enzyme α-glucosidase by interacting with two prominent amino acids, ASP568 and PHE601, at the binding site on the target enzyme, creating six linkages and showing a better binding energy score (−14.6 kcal/mol) than acarbose (−10.5 kcal/mol). The results of this work suggest that cassava wastewater can serve as a low-cost raw material for the effective production of PG, a potential antidiabetic drug candidate.

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Lepidine B from Lepidium Sativum Seeds as Multi-Functional Anti-Alzheimer’s Disease Agent: In Vitro and In Silico Studies

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200302120305 ◽

2020 ◽

Vol 16 ◽

Cited By ~ 1

Author(s):

Talia Serseg ◽

Khedidja Benarous ◽

Meriem Lamrani ◽

Mohamed Yousfi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Docking Study ◽

Inhibitory Effect ◽

Positive Control ◽

Lepidium Sativum ◽

Drug Candidate ◽

Juniperus Oxycedrus ◽

In Silico Studies ◽

Juniperus Phoenicea

Objective: The present study is carried out to screen the anticholinesterase effect of the total alkaloids of L. sativum seeds and other plants, and studied the ability of Lepidine B to inhibit AChE, BuChE, BACE and MAGL. and the main interactions in inhibitor-enzyme complex. Method: Inhibitory effect extracts from Lepidium sativum, Juniperus phoenicea and Juniperus oxycedrus on acetylcholinesterase using Ellman method have been investigated using Donepezil as positive control. Molecular docking study carried out using Autodock vina. The structures of studied molecules Lepidine B, Galantamine and Donepezil were obtained from PubChem database and Protein databank. Results: Alkaloidal extract of Lepidium sativum and ethyl acetate extracts of Juniperus phoenicea and Juniperus oxycedrus exhibit a strong acetylcholinesterase inhibitory activity with IC50 values of 0.59 ± 0.04, 0.57 ± 0.00 and 0.49 ± 0.00 mg/mL, respectively using Donepezil <0.25 mg/mL as positive control. The major component of alkaloid of L. sativum, Lepidine B bind so tightly to AChE and BuChE as much as galantamine and donepezil. We suggest that Lepidine B is a non-competitive inhibitory by interacting with PAS of AChE and BuChE, therefore it is capable to prevent the HuAChE-induced Aβ aggregation. We have found significant interactions in the Lepidine B-BACE and Lepidine B-MAGL complexes. Conclusion: The docking study indicate that Lepidine B is a promising anti-AD drug and might become a drug candidate to prevent Alzheimer's disease due to its multiple roles as potent inhibitor for AChE, BuChE, BACE and MAGL, also inhibitor for Aβ fibrillogenesis. No previous results about the inhibitory effect Lepidine B on the AChE, BuChE, β secretase and monoacylglycerol lipase have been reported.

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Synthesis and Assessment of Novel Anti-chlamydial Benzylidene Acylhydrazides Derivatives

Letters in Drug Design & Discovery ◽

10.2174/1570180814666170526170227 ◽

2018 ◽

Vol 15 (1) ◽

pp. 31-36 ◽

Cited By ~ 5

Author(s):

Xiaofeng Bao ◽

Ying Xue ◽

Chao Xia ◽

Yin Lu ◽

Ningjing Yang ◽

...

Keyword(s):

Inhibitory Effect ◽

Dependent Manner ◽

Iron Starvation ◽

Hydrochloride Salt ◽

Obligate Intracellular ◽

Biphasic Life Cycle ◽

Ic50 Value ◽

Ic50 Values ◽

Dose Dependent ◽

Better Than

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

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Molecular Docking Study for Analyzing the Inhibitory Effect of Anti-inflammatory Plant Compound Against Tumour Necrosis Factor (TNF-α)

Current Drug Therapy ◽

10.2174/1574885513666180503145352 ◽

2019 ◽

Vol 14 (1) ◽

pp. 85-90

Author(s):

Sagarika Biswas

Keyword(s):

Molecular Docking ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Docking Study ◽

Developed Countries ◽

Inhibitory Effect ◽

Molecular Docking Study ◽

Drug Designing ◽

Anti Inflammatory ◽

Necrosis Factor

Background: Rheumatoid Arthritis (RA) is an autoimmune disorder of symmetric synovial joints which is characterized by the chronic inflammation with 0.5-1% prevalence in developed countries. Presence of persistent inflammation is attributed to the major contribution of key inflammatory cytokine and tumour necrosis factor- alpha (TNF- α). Recent drug designing studies are developing TNF-α blockers to provide relief from the symptoms of the disease such as pain and inflammation. Available blockers are showing certain limitations such as it may enhance the rate of tuberculosis (TB) occurrence, lymphoma risk, cost issues and certain infections are major concern. Discussed limitations implicated a need of development of some alternative drugs which exhibit fewer side effects with low cost. Therefore, we have identified anti-inflammatory compounds in an underutilized fruit of Baccaurea sapida (B.sapida) in our previous studies. Among them quercetin have been identified as the most potent lead compound for drug designing studies of RA. Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- α and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA. Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-α and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 µM inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-α in RA compared to control. Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-α mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.

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Regulation of Swarming Motility and flhDCSm Expression by RssAB Signaling in Serratia marcescens

Journal of Bacteriology ◽

10.1128/jb.01670-07 ◽

2008 ◽

Vol 190 (7) ◽

pp. 2496-2504 ◽

Cited By ~ 25

Author(s):

Po-Chi Soo ◽

Yu-Tze Horng ◽

Jun-Rong Wei ◽

Jwu-Ching Shu ◽

Chia-Chen Lu ◽

...

Keyword(s):

Serratia Marcescens ◽

Binding Site ◽

Promoter Region ◽

Transcriptional Start Site ◽

Direct Interaction ◽

Underlying Mechanism ◽

Inhibitory Effect ◽

Start Codon ◽

Mobility Shift

ABSTRACT Serratia marcescens cells swarm at 30°C but not at 37°C, and the underlying mechanism is not characterized. Our previous studies had shown that a temperature upshift from 30 to 37°C reduced the expression levels of flhDCSm and hagSm in S. marcescens CH-1. Mutation in rssA or rssB, cognate genes that comprise a two-component system, also resulted in precocious swarming phenotypes at 37°C. To further characterize the underlying mechanism, in the present study, we report that expression of flhDCSm and synthesis of flagella are significantly increased in the rssA mutant strain at 37°C. Primer extension analysis for determination of the transcriptional start site(s) of flhDCSm revealed two transcriptional start sites, P1 and P2, in S. marcescens CH-1. Characterization of the phosphorylated RssB (RssB∼P) binding site by an electrophoretic mobility shift assay showed direct interaction of RssB∼P, but not unphosphorylated RssB [RssB(D51E)], with the P2 promoter region. A DNase I footprinting assay using a capillary electrophoresis approach further determined that the RssB∼P binding site is located between base pair positions −341 and −364 from the translation start codon ATG in the flhDCSm promoter region. The binding site overlaps with the P2 “−35” promoter region. A modified chromatin immunoprecipitation assay was subsequently performed to confirm that RssB∼P binds to the flhDCSm promoter region in vivo. In conclusion, our results indicated that activated RssA-RssB signaling directly inhibits flhDCSm promoter activity at 37°C. This inhibitory effect was comparatively alleviated at 30°C. This finding might explain, at least in part, the phenomenon of inhibition of S. marcescens swarming at 37°C.

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Combined Ensemble Docking and Machine Learning in Identification of Therapeutic Agents with Potential Inhibitory Effect on Human CES1

Molecules ◽

10.3390/molecules24152747 ◽

2019 ◽

Vol 24 (15) ◽

pp. 2747 ◽

Cited By ~ 1

Author(s):

Eliane Briand ◽

Ragnar Thomsen ◽

Kristian Linnet ◽

Henrik Berg Rasmussen ◽

Søren Brunak ◽

...

Keyword(s):

Machine Learning ◽

Drug Interactions ◽

Scoring Function ◽

Docking Study ◽

Inhibitory Effect ◽

Therapeutic Agents ◽

Learning Approaches ◽

Ensemble Docking ◽

Ic50 Values

The human carboxylesterase 1 (CES1), responsible for the biotransformation of many diverse therapeutic agents, may contribute to the occurrence of adverse drug reactions and therapeutic failure through drug interactions. The present study is designed to address the issue of potential drug interactions resulting from the inhibition of CES1. Based on an ensemble of 10 crystal structures complexed with different ligands and a set of 294 known CES1 ligands, we used docking (Autodock Vina) and machine learning methodologies (LDA, QDA and multilayer perceptron), considering the different energy terms from the scoring function to assess the best combination to enable the identification of CES1 inhibitors. The protocol was then applied on a library of 1114 FDA-approved drugs and eight drugs were selected for in vitro CES1 inhibition. An inhibition effect was observed for diltiazem (IC50 = 13.9 µM). Three others drugs (benztropine, iloprost and treprostinil), exhibited a weak CES1 inhibitory effects with IC50 values of 298.2 µM, 366.8 µM and 391.6 µM respectively. In conclusion, the binding site of CES1 is relatively flexible and can adapt its conformation to different types of ligands. Combining ensemble docking and machine learning approaches improves the prediction of CES1 inhibitors compared to a docking study using only one crystal structure.

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Heterocyclic Aromatic Amines in Meat: Formation, Isolation, Risk Assessment and Inhibitory Effect of Plant Extracts

Foods ◽

10.3390/foods10071466 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1466

Author(s):

Hafiz Rehan Nadeem ◽

Saeed Akhtar ◽

Tariq Ismail ◽

Piero Sestili ◽

Jose Manuel Lorenzo ◽

...

Keyword(s):

Risk Assessment ◽

Plant Extracts ◽

Aromatic Amines ◽

Extraction Procedure ◽

Inhibitory Effect ◽

Heating Time ◽

Raw Material ◽

Heterocyclic Aromatic Amines ◽

Isolation And Identification ◽

Cooked Meats

Heterocyclic aromatic amines (HAAs) are potent carcinogenic compounds induced by the Maillard reaction in well-done cooked meats. Free amino acids, protein, creatinine, reducing sugars and nucleosides are major precursors involved in the production of polar and non-polar HAAs. The variety and yield of HAAs are linked with various factors such as meat type, heating time and temperature, cooking method and equipment, fresh meat storage time, raw material and additives, precursor’s presence, water activity, and pH level. For the isolation and identification of HAAs, advanced chromatography and spectroscopy techniques have been employed. These potent mutagens are the etiology of several types of human cancers at the ng/g level and are 100- to 2000-fold stronger than that of aflatoxins and benzopyrene, respectively. This review summarizes previous studies on the formation and types of potent mutagenic and/or carcinogenic HAAs in cooked meats. Furthermore, occurrence, risk assessment, and factors affecting HAA formation are discussed in detail. Additionally, sample extraction procedure and quantification techniques to determine these compounds are analyzed and described. Finally, an overview is presented on the promising strategy to mitigate the risk of HAAs by natural compounds and the effect of plant extracts containing antioxidants to reduce or inhibit the formation of these carcinogenic substances in cooked meats.

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Removal of Cadmium(II) from Water using Modified Citrus limettioides Peels: Thermodynamic and Isotherm Studies

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22278 ◽

2019 ◽

Vol 32 (1) ◽

pp. 73-78

Author(s):

P. Janaki ◽

R. Sudha ◽

T.S. Sribharathi ◽

P. Anitha ◽

K. Poornima ◽

...

Keyword(s):

Adsorption Process ◽

Low Cost ◽

Raw Material ◽

Isotherm Models ◽

Batch Adsorption ◽

Adsorption Method ◽

Chemically Modified ◽

Adsorption Performance ◽

Monolayer Adsorption ◽

Isotherm Equations

The adsorption performance of sulphuric acid treated low cost adsorbent synthesized by using Citrus limettioides peel as an effective raw material for the removal of cadmium(II) from water. The batch adsorption method was carried out to optimize some parameters like contact time, pH and adsorbent dose. The nonlinear isotherm equations were used to calculate the different isotherm constant of five isotherm models namely Freundlich, Langmuir, Dubinin-Radushkevich, Redlich-Peterson and Sips. The Langmuir monolayer adsorption capacity of chemically modified Citrus limettioides peel was found to be 287.60 mg g-1. The negative values of ΔGº and ΔHº showed that the adsorption process is spontaneous and exothermic.

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Feasibility of cereal straw for industrial utilization in Minnesota

American Journal of Alternative Agriculture ◽

10.1017/s0889189300008407 ◽

2000 ◽

Vol 15 (1) ◽

pp. 2-8 ◽

Cited By ~ 2

Author(s):

N.C. Wagner ◽

S. Ramaswamy ◽

U. Tschirner

Keyword(s):

Animal Feed ◽

Raw Materials ◽

Low Cost ◽

Economic Feasibility ◽

Raw Material ◽

Cereal Straw ◽

Industrial Utilization ◽

Industrial Use ◽

On Farm ◽

And Storage

AbstractA pre-economic feasibility study was undertaken to determine the potential of cereal straw for industrial utilization in Minnesota. Specifically, utilizing straw for pulp and paper manufacture was of interest. The availability of cereal straw fiber supplies at various locations across the state of Minnesota, along with pre-processing issues such as transportation, harvesting, handling, and storage, are discussed and priced. The greatest economic advantage of straw for industrial use appears to be the low cost of the raw material compared to traditional raw materials. This also provides an excellent opportunity for additional income for farmers. The methodology and information provided here should be helpful in evaluating the feasibility of utilizing straw for other industrial purposes in other parts of the world. However, in some Third World countries, long-standing on-farm, traditional uses of cereal straws for fuel, fiber, and animal feed may limit their availability for industrial utilization.

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Diadenosine polyphosphate hydrolase from presynaptic plasma membranes of Torpedo electric organ

Biochemical Journal ◽

10.1042/bj3230677 ◽

1997 ◽

Vol 323 (3) ◽

pp. 677-684 ◽

Cited By ~ 21

Author(s):

Jesús MATEO ◽

Pedro ROTLLAN ◽

Eulalia MARTI ◽

Inmaculada GOMEZ DE ARANDA ◽

Carles SOLSONA ◽

...

Keyword(s):

Plasma Membranes ◽

Pyridoxal Phosphate ◽

Electric Organ ◽

Competitive Inhibitor ◽

Inhibitory Effect ◽

Ic50 Value ◽

Neural Origin ◽

Disulphonic Acid ◽

Torpedo Electric Organ ◽

Enzyme Activators

The diadenosine polyphosphate hydrolase present in presynaptic plasma membranes from the Torpedo electric organ has been characterized using fluorogenic substrates of the form di-(1,N6-ethenoadenosine) 5´,5‴-P1,Pn-polyphosphate. The enzyme hydrolyses diadenosine polyphosphates (Apn A, where n = 3–5), producing AMP and the corresponding adenosine (n-1) 5´-phosphate, Ap(n-1). The Km values of the enzyme were 0.543± 0.015, 0.478±0.043 and 0.520±0.026 μM, and the Vmax values were 633±4, 592±18 and 576±45 pmol/min per mg of protein, for the etheno derivatives of Ap3A (adenosine 5´,5‴-P1,P3-triphosphate), Ap4A (adenosine 5´,5‴-P1,P4 -tetraphosphate) and Ap5A (adenosine 5´,5‴-P1,P5-pentaphosphate) respectively. Ca2+, Mg2+ and Mn2+ are enzyme activators, with EC50 values of 0.86±0.11, 1.35±0.24 and 0.58±0.10 mM respectively. The fluoride ion is an inhibitor with an IC50 value of 1.38±0.19 mM. The ATP analogues adenosine 5´-tetraphosphate and adenosine 5´-[γ-thio]triphosphate are potent competitive inhibitors and adenosine 5´-[α,β-methylene]diphosphate is a less potent competitive inhibitor, the Ki values being 0.29±0.03, 0.43±0.05 and 7.18±0.8 μM respectively. The P2-receptor antagonist pyridoxal phosphate 6-azophenyl-2´,4´-disulphonic acid behaves as a non-competitive inhibitor with a Ki value of 29.7±3.1 μM, and also exhibits a significant inhibitory effect on Torpedo apyrase activity. The effect of pH on the Km and Vmax values, together with inhibition by diethyl pyrocarbonate, strongly suggests the presence of functional histidine residues in Torpedo diadenosine polyphosphate hydrolase. The enzyme from Torpedo shows similarities with that of neural origin from neurochromaffin cells, and significant differences compared with that from endothelial vascular cells.

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Advances in absorbents and techniques used in wet and dry FGD: a critical review

Reviews in Chemical Engineering ◽

10.1515/revce-2020-0029 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Lokesh Kumar ◽

Susanta Kumar Jana

Keyword(s):

Power Plants ◽

Low Cost ◽

Fine Particulate Matter ◽

Packed Column ◽

Toxic Substance ◽

Cost Effective ◽

Solid Wastes ◽

Raw Material ◽

Process Industries ◽

Slurry Bubble Columns

Abstract Sulfur dioxide is considered as an extremely harmful and toxic substance among the air pollutants emitted from the lignite- and other high-sulfur-coal based power plants, old tires processing units, smelters, and many other process industries. Various types of absorbents and desulfurization technologies have been developed and adopted by the industries to reduce the emission rate of SO2 gas. The present paper focuses on the ongoing advances in the development of varieties of regenerative and non-regenerative absorbents viz., Ca-based, Mg-based, Fe-based, Na-based, N2-based, and others along with various FGD technology, viz., wet, dry or semi-dry processes. Additionally, different types of contactors viz., packed column, jet column, spray tower, and slurry bubble columns along with their significant operational and design features have also been discussed. In the existing or newly installed limestone-based FGD plants, an increasing trend of the utilization of newly developed technologies such as limestone forced oxidation (LSFO) and magnesium-enhanced lime (MEL) are being used at an increasing rate. However, the development of low-cost sorbents, particularly suitable solid wastes, for the abatement of SO2 emission needs to be explored sincerely. Many such wastes cause air pollution by way of entrainment of fine particulate matter (PM), groundwater contamination by its leaching, or brings damage to crops due to its spreading onto the cultivation land. One such pollutant is marble waste and in this work, this has been suggested as a suitable substitute to limestone and cost-effective sorbent for the desulfurization of flue gases. The product of this process being sellable in the market or may be used as a raw material in several industries, it can also prove to be an important route of recycling and reuse of one of the air and water-polluting solid wastes.

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