scholarly journals Mining Invertebrate Natural Products for Future Therapeutic Treasure

2011 ◽  
Vol 6 (9) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Youmie Park
Keyword(s):  
Biological Activities ◽  
Structure Characterization ◽  
Biologically Active ◽  
Cone Snail ◽  
Drug Candidates ◽  
Research Areas ◽  
Natural Medicine ◽  
Biological Compounds ◽  
Insight Into

This review focuses on biologically active entities from invertebrate sources, especially snails. The reader will encounter several categories of compounds from snails including glycosaminoglycans, peptides, proteins (glycoproteins), and enzymes which possess diverse biological activities. Among glycosaminoglycans, acharan sulfate which was isolated from a giant African snail Acahtina fulica is reviewed extensively. Conotoxins which are also called conopeptides are unique peptide mixtures from marine cone snail. Conotoxins are secreted to capture its prey, and currently have the potential to be highly effective drug candidates. One of the conotoxins is now in the market as a pain killer. Proteins as well as glycoproteins in the snail are known to be involved in the host defense process from an attack of diverse pathogens. Carbohydrate-degrading enzymes characterized and purified in snails are introduced to give an insight into the applicability in glycobiology research such as synthesis and structure characterization of glycoconjugates. It seems that simple snails produce very complicated biological compounds which could be an invaluable source in future therapeutics as well as research areas in natural medicine.

scholarly journals Cloning and Partial Characterization of an Endo-α-(1→6)-d-Mannanase Gene from Bacillus circulans

2019 ◽  
Vol 20 (24) ◽  
pp. 6244 ◽  
Author(s):  
Shiva kumar Angala ◽  
Wei Li ◽  
Zuzana Palčeková ◽  
Lu Zou ◽  
Todd L. Lowary ◽  
...  
Keyword(s):  
Biological Activities ◽  
Glycosyl Hydrolase ◽  
Bacillus Circulans ◽  
Branching Patterns ◽  
Broad Array ◽  
Covalent Modifications ◽  
Insight Into ◽  
Accessible Form ◽  
Successful Production

Mycobacteria produce two major lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM), whose broad array of biological activities are tightly related to the fine details of their structure. However, the heterogeneity of these molecules in terms of internal and terminal covalent modifications and complex internal branching patterns represent significant obstacles to their structural characterization. Previously, an endo-α-(1→6)-D-mannanase from Bacillus circulans proved useful in cleaving the mannan backbone of LM and LAM, allowing the reducing end of these molecules to be identified as Manp-(1→6) [Manp-(1→2)]-Ino. Although first reported 45 years ago, no easily accessible form of this enzyme was available to the research community, a fact that may in part be explained by a lack of knowledge of its complete gene sequence. Here, we report on the successful cloning of the complete endo-α-(1→6)-D-mannanase gene from Bacillus circulans TN-31, herein referred to as emn. We further report on the successful production and purification of the glycosyl hydrolase domain of this enzyme and its use to gain further insight into its substrate specificity using synthetic mannoside acceptors as well as LM and phosphatidyl-myo-inositol mannoside precursors purified from mycobacteria.

scholarly journals Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4835
Author(s):  
Krzesimir Ciura ◽  
Joanna Fedorowicz ◽  
Petar Žuvela ◽  
Mario Lovrić ◽  
Hanna Kapica ◽  
...  
Keyword(s):  
Water System ◽  
Reversed Phase ◽  
Biologically Active ◽  
Flash Method ◽  
Artificial Membrane ◽  
Drug Candidates ◽  
Immobilized Artificial Membrane ◽  
Phase Liquid ◽  
Getaway Descriptors

Currently, rapid evaluation of the physicochemical parameters of drug candidates, such as lipophilicity, is in high demand owing to it enabling the approximation of the processes of absorption, distribution, metabolism, and elimination. Although the lipophilicity of drug candidates is determined using the shake flash method (n-octanol/water system) or reversed phase liquid chromatography (RP-LC), more biosimilar alternatives to classical lipophilicity measurement are currently available. One of the alternatives is immobilized artificial membrane (IAM) chromatography. The present study is a continuation of our research focused on physiochemical characterization of biologically active derivatives of isoxazolo[3,4-b]pyridine-3(1H)-ones. The main goal of this study was to assess the affinity of isoxazolones to phospholipids using IAM chromatography and compare it with the lipophilicity parameters established by reversed phase chromatography. Quantitative structure–retention relationship (QSRR) modeling of IAM retention using differential evolution coupled with partial least squares (DE-PLS) regression was performed. The results indicate that in the studied group of structurally related isoxazolone derivatives, discrepancies occur between the retention under IAM and RP-LC conditions. Although some correlation between these two chromatographic methods can be found, lipophilicity does not fully explain the affinities of the investigated molecules to phospholipids. QSRR analysis also shows common factors that contribute to retention under IAM and RP-LC conditions. In this context, the significant influences of WHIM and GETAWAY descriptors in all the obtained models should be highlighted.

3,4-Dihydroisocoumarins, Interesting Natural Products: Isolation, Organic Syntheses and Biological Activities

2019 ◽  
Vol 16 (1) ◽  
pp. 112-129 ◽  
Author(s):  
Aurelio Ortiz ◽  
Miriam Castro ◽  
Estibaliz Sansinenea
Keyword(s):  
Natural Products ◽  
Biological Activities ◽  
Natural Compounds ◽  
Biologically Active ◽  
Bacterial Strains ◽  
Drug Candidates ◽  
Heterocyclic Molecules ◽  
Naturally Occurring ◽  
Wide Range ◽  
Different Sources

Background:3,4-dihydroisocoumarins are an important small group belonging to the class of naturally occurring lactones isolated from different bacterial strains, molds, lichens, and plants. The structures of these natural compounds show various types of substitution in their basic skeleton and this variability influences deeply their biological activities. These lactones are structural subunits of several natural products and serve as useful intermediates in the synthesis of different heterocyclic molecules, which exhibit a wide range of biological activities, such as anti-inflammatory, antiplasmodial, antifungal, antimicrobial, antiangiogenic and antitumoral activities, among others. Their syntheses have attracted attention of many researchers reporting many synthetic strategies to achieve 3,4-dihydroisocoumarins and other related structures. </P><P> Objective: In this context, the isolation of these natural compounds from different sources, their syntheses and biological activities are reviewed, adding the most recent advances and related developments.Conclusion:This review aims to encourage further work on the isolation and synthesis of this class of natural products. It would be beneficial for synthetic as well as the medicinal chemists to design selective, optimized dihydroisocoumarin derivatives as potential drug candidates, since dihydroisocoumarin scaffolds have significant utility in the development of therapeutically relevant and biologically active compounds.

Synthesis and In silico Studies of Quinazolinone Derivatives as PARP-1 Inhibitors

2020 ◽  
Vol 17 (12) ◽  
pp. 1552-1565
Author(s):  
Sonia Verma ◽  
Akashdeep Singh Pathania ◽  
Somesh Baranwal ◽  
Pradeep Kumar
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Docking Studies ◽  
Biologically Active ◽  
Reference Drug ◽  
Drug Candidates ◽  
In Silico Studies ◽  
Antileishmanial Activities ◽  
Quinazolinone Derivatives ◽  
Parp 1

Background: Cancer is a leading cause of deaths worldwide, accounting for 9.6 million deaths in 2018. According to the WHO, the most common causes of cancer deaths are lung, colorectal, stomach liver and breast cancer. Introduction: PARP-1 has a crucial role in cell proliferation, survival and death due to its role in the regulation of multiple biological processes. Quinazolinone and its derivatives represent a large class of biologically active compounds that exhibit a broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant and antileishmanial activities. Methods: In this study, we have synthesized quinazolinone derivatives by reaction of 2- aminobenzamide and substituted benzaldehydes. The synthesized compounds were also screened in silico for their PARP-1 binding affinities by molecular docking studies using Schrodinger 2016 software. In silico ADME studies were also performed for the synthesized compounds by using QikProp tool of Schrodinger software. Results: Results of in silico studies indicated that quinazolinone derivatives exhibited a good affinity towards the active site of PARP-1. Out of all synthesized compounds, SVA-11 exhibited a maximum dock score (-10.421). Results of ADME studies indicated the suitability of synthesized compounds as drug candidates. Conclusion: The synthesized compounds showed better docking scores than reference drug valiparib. Furthermore, they exhibited favorable ADME profile. Therefore, they may serve as lead compounds in the discovery of PARP-1 inhibitors.

Immunochemical and biological characterization of calcitonin originating from transplanted medullary thyroid carcinoma in rats

1982 ◽  
Vol 99 (3) ◽  
pp. 397-403 ◽  
Author(s):  
Lisbeth Myhre ◽  
Arne Ekeland ◽  
Kaare M. Gautvik
Keyword(s):  
Biological Activities ◽  
Gel Filtration ◽  
Molecular Size ◽  
Serum Levels ◽  
Biologically Active ◽  
Subcutaneous Injections ◽  
Medullary Thyroid ◽  
Biological Potency ◽  
Medullary Thyroid Carcinomas

Abstract. The immunoreactive and biological activities of calcitonin (CT) produced by transplanted rat medullary thyroid carcinomas (MCT) have been studied. Immunoreactive CT (iCT) in serum and in MCT tissues of rats carrying tumours of generations 5–8 was characterized by gel filtration on Sephadex G-100 followed by radioimmunological measurements using region specific antiserum. The hypocalcaemic effect of sera and tumour extracts was tested in a rat bioassay. Rats with transplanted MCT of the 5th and 6th generations had mainly (70–84%) circulating iCT species of molecular size comparable to intact hormone. However, in rats with tumours of the 7th and 8th generations corresponding circulating iCT forms comprised less than 52% of total immunoreactivity while 32–38% eluted earlier. In conparison, iCT corresponding to intact hormone represented 30–50% of total immunoreactivity in the tumour extracts and no differences were observed between the generations. Subcutaneous injections of sera from MCT rats and of tumour extracts reduced the serum levels of ionized calcium in test rats. The sera containing mainly intact iCT showed the strongest biological potency. We conclude that rat MCT transplanted under the kidney capsule is able to secrete biologically active CT. However, the heterogeneity of circulating iCT increases in rats with transplanted tumours of older generations, approaching the heterogeneity of stored hormone in the gland.

scholarly journals Insight Into Molecular Determinants of T3 vs T4 Recognition From Mutations in Thyroid Hormone Receptor α and β

2019 ◽  
Vol 104 (8) ◽  
pp. 3491-3500 ◽  
Author(s):  
Karn Wejaphikul ◽  
Stefan Groeneweg ◽  
Yvonne Hilhorst-Hofstee ◽  
V Krishna Chatterjee ◽  
Robin P Peeters ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Thyroid Hormone Receptor ◽  
Radioligand Binding ◽  
Fundamental Principle ◽  
Biologically Active ◽  
Molecular Determinants ◽  
Structural Mechanisms ◽  
Thyroid Hormone Receptor Α ◽  
Insight Into

Abstract Context The two major forms of circulating thyroid hormones (THs) are T3 and T4. T3 is regarded as the biologically active hormone because it binds to TH receptors (TRs) with greater affinity than T4. However, it is currently unclear what structural mechanisms underlie this difference in affinity. Objective Prompted by the identification of a novel M256T mutation in a resistance to TH (RTH)α patient, we investigated Met256 in TRα1 and the corresponding residue (Met310) in TRβ1, residues previously predicted by crystallographic studies in discrimination of T3 vs T4. Methods Clinical characterization of the RTHα patient and molecular studies (in silico protein modeling, radioligand binding, transactivation, and receptor–cofactor studies) were performed. Results Structural modeling of the TRα1-M256T mutant showed that distortion of the hydrophobic niche to accommodate the outer ring of ligand was more pronounced for T3 than T4, suggesting that this substitution has little impact on the affinity for T4. In agreement with the model, TRα1-M256T selectively reduced the affinity for T3. Also, unlike other naturally occurring TRα mutations, TRα1-M256T had a differential impact on T3- vs T4-dependent transcriptional activation. TRα1-M256A and TRβ1-M310T mutants exhibited similar discordance for T3 vs T4. Conclusions Met256-TRα1/Met310-TRβ1 strongly potentiates the affinity of TRs for T3, thereby largely determining that T3 is the bioactive hormone rather than T4. These observations provide insight into the molecular basis for underlying the different affinity of TRs for T3 vs T4, delineating a fundamental principle of TH signaling.

scholarly journals Green Synthetic Approach: An Efficient Eco-Friendly Tool for Synthesis of Biologically Active Oxadiazole Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1163
Author(s):  
Bimal Krishna Banik ◽  
Biswa Mohan Sahoo ◽  
Bera Venkata Varaha Ravi Kumar ◽  
Krishna Chandra Panda ◽  
Jasma Jena ◽  
...  
Keyword(s):  
Microwave Irradiation ◽  
Biological Activities ◽  
Product Yield ◽  
Biologically Active ◽  
Synthetic Approach ◽  
Green Protocol ◽  
Drug Candidates ◽  
New Drug ◽  
Drug Molecules ◽  
Oxadiazole Derivatives

Green synthetic protocol refers to the development of processes for the sustainable production of chemicals and materials. For the synthesis of various biologically active compounds, energy-efficient and environmentally benign processes are applied, such as microwave irradiation technology, ultrasound-mediated synthesis, photo-catalysis (ultraviolet, visible and infrared irradiation), molecular sieving, grinding and milling techniques, etc. Thesemethods are considered sustainable technology and become valuable green protocol to synthesize new drug molecules as theyprovidenumerous benefits over conventional synthetic methods.Based on this concept, oxadiazole derivatives are synthesized under microwave irradiation technique to reduce the formation of byproduct so that the product yield can be increased quantitatively in less reaction time. Hence, the synthesis of drug molecules under microwave irradiation follows a green chemistry approach that employs a set of principles to minimize or remove the utilization and production of hazardous toxic materials during the design, manufacture and application of chemical substances.This approach plays a major role in controlling environmental pollution by utilizing safer solvents, catalysts, suitable reaction conditions and thereby increases the atom economy and energy efficiency. Oxadiazole is a five-membered heterocyclic compound that possesses one oxygen and two nitrogen atoms in the ring system.Oxadiazole moiety is drawing considerable interest for the development of new drug candidates with potential therapeutic activities including antibacterial, antifungal, antiviral, anticonvulsant, anticancer, antimalarial, antitubercular, anti-asthmatic, antidepressant, antidiabetic, antioxidant, antiparkinsonian, analgesic and antiinflammatory, etc. This review focuses on different synthetic approaches of oxadiazole derivatives under microwave heating method and study of their various biological activities.

scholarly journals Synthesis and structure characterization of biologically active triphenyltin complexes with thioamides

2015 ◽  
Vol 71 (a1) ◽  
pp. s432-s433
Author(s):  
Agata Owczarzak ◽  
Anita Owczrzak ◽  
Maciej Kubicki ◽  
Marek Murias ◽  
Małgorzat Kucińska
Keyword(s):  
Structure Characterization ◽  
Biologically Active

scholarly journals Annexin proteins PP4 and PP4-X. Comparative characterization of biological activities of placental and recombinant proteins

1990 ◽  
Vol 272 (1) ◽  
pp. 223-229 ◽  
Author(s):  
J Römisch ◽  
M Grote ◽  
K U Weithmann ◽  
N Heimburger ◽  
E Amann
Keyword(s):  
Escherichia Coli ◽  
Phospholipase A2 ◽  
Recombinant Proteins ◽  
Physicochemical Parameters ◽  
Biological Activities ◽  
Inhibition Test ◽  
Biologically Active ◽  
High Yield ◽  
A Minor

The human placental proteins PP4 and PP4-X, belonging to the annexin protein family, were expressed in Escherichia coli at high yield. The proteins were purified to homogeneity. The physicochemical parameters of the recombinant proteins were determined and compared with those of their natural placental counterparts. Except for a minor change in the pI, the proteins appeared to be indistinguishable by several criteria. Both recombinant PP4 and recombinant PP4-X were biologically active in a thromboplastin inhibition test and in a phospholipase A2 inhibition test.

Sign in / Sign up

Export Citation Format

Share Document