C1-Inhibitor: Structure, Functional Diversity and Therapeutic Development

2021 ◽  
Vol 28 ◽  
Author(s):  
Elena Karnaukhova
Keyword(s):  
Biochemical Characterization ◽  
Biological Activities ◽  
Serine Proteinase ◽  
Endotoxin Shock ◽  
C1 Inhibitor ◽  
Recent Advances ◽  
Therapeutic Development ◽  
Inhibitory Activities ◽  
Endogenous Proteins ◽  
C1inh Deficiency

: Human C1-Inhibitor (C1INH), also known as C1-esterase inhibitor, is an important multifunctional plasma glycoprotein that is uniquely involved in a regulatory network of complement, contact, coagulation, and fibrinolytic systems. C1INH belongs to a superfamily of serine proteinase inhibitor (serpins) and exhibits its inhibitory activities towards several target proteases of plasmatic cascades, operating as a major anti-inflammatory protein in the circulation. In addition to its inhibitory activities, C1INH is also involved in non-inhibitory interactions with some endogenous proteins, polyanions, cells and infectious agents. While C1INH is essential for multiple physiological processes, it is better known for its deficiency with regards to Hereditary Angioedema (HAE), a rare autosomal dominant disease clinically manifested by recurrent acute attacks of increased vascular permeability and edema. Since the link was first established between functional C1INH deficiency in plasma and HAE in the 1960s, tremendous progress has been made in the biochemical characterization of C1INH and its therapeutic development for replacement therapies in patients with C1INH-dependent HAE. Various C1INH biological activities, recent advances in the HAE-targeted therapies, and availability of C1INH commercial products have prompted intensive investigation of the C1INH potential for treatment of clinical conditions other than HAE. This article provides an updated overview of the structure and biological activities of C1INH, its role in HAE pathogenesis, and recent advances in the research and therapeutic development of C1INH; it also considers some trends for using C1INH therapeutic preparations for applications other than angioedema, from sepsis and endotoxin shock to severe thrombotic complications in COVID-19 patients.

scholarly journals Recent Advances in Sorbicillinoids from Fungi and Their Bioactivities (Covering 2016–2021)

2022 ◽  
Vol 8 (1) ◽  
pp. 62
Author(s):  
Xuwen Hou ◽  
Xuping Zhang ◽  
Mengyao Xue ◽  
Zhitong Zhao ◽  
Huizhen Zhang ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structural Features ◽  
Phytopathogenic Fungi ◽  
Side Chain ◽  
Recent Advances ◽  
Inhibitory Activities ◽  
Anti Inflammatory

Sorbicillinoids are a family of hexaketide metabolites with a characteristic sorbyl side chain residue. Sixty-nine sorbicillinoids from fungi, newly identified from 2016 to 2021, are summarized in this review, including their structures and bioactivities. They are classified into monomeric, dimeric, trimeric, and hybrid sorbicillinoids according to their basic structural features, with the main groups comprising both monomeric and dimeric sorbicillinoids. Some of the identified sorbicillinoids have special structures such as ustilobisorbicillinol A, and sorbicillasins A and B. The majority of sorbicillinoids have been reported from fungi genera such as Acremonium, Penicillium, Trichoderma, and Ustilaginoidea, with some sorbicillinoids exhibiting cytotoxic, antimicrobial, anti-inflammatory, phytotoxic, and α-glucosidase inhibitory activities. In recent years, marine-derived, extremophilic, plant endophytic, and phytopathogenic fungi have emerged as important resources for diverse sorbicillinoids with unique skeletons. The recently revealed biological activities of sorbicillinoids discovered before 2016 are also described in this review.

Reactivity of Barbituric, Thiobarbituric Acids and Their Related Analogues: Synthesis of Substituted and Heterocycles-based Pyrimidines

2020 ◽  
Vol 24 (14) ◽  
pp. 1610-1642 ◽  
Author(s):  
Ahmed El-Mekabaty ◽  
Hassan A. Etman ◽  
Ahmed Mosbah ◽  
Ahmed A. Fadda
Keyword(s):  
Xanthine Oxidase ◽  
Multicomponent Reactions ◽  
Biological Activities ◽  
Present Review ◽  
Urease Inhibitors ◽  
Effective Catalyst ◽  
Inhibitory Activities ◽  
Catalyst Reusability ◽  
High Yields ◽  
Nano Catalysts

Barbituric, thiobarbituric acids and their related analogs are reactive synthons for the synthesis of drugs and biologically, and pharmaceutically active pyrimidines. The present review aimed to summarize the recent advances in the synthesis of different alkylsubstituted, fused cycles, spiro-, and binary heterocycles incorporated pyrimidine skeleton based on barbituric derivatives. In this sequence, the eco-friendly techniques under catalytic conditions were used for the diverse types of multicomponent reactions under different conditions for the synthesis of various types of heterocycles. Nano-catalysts are efficient for the synthesis of these compounds in high yields and effective catalyst reusability. The compounds are potent antibacterial, cytotoxic, xanthine oxidase inhibitory activities, and attend as urease inhibitors. The projected mechanisms for the synthesis of pyranopyrimidines, benzochromenopyrimidines, chromeno-pyranopyrimidines, spiroxyindoles, oxospiro-tricyclic furopyrimidines, pyrimidine-based monoand bicyclic pyridines were discussed. The potent and diverse biological activities for instance, antioxidant, antibacterial, cytotoxic, and xanthine oxidase inhibitory activities, as well as urease inhibitors, are specified.

Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present

2020 ◽  
Vol 20 (10) ◽  
pp. 908-920 ◽  
Author(s):  
Su-Min Wu ◽  
Xiao-Yang Qiu ◽  
Shu-Juan Liu ◽  
Juan Sun
Keyword(s):  
Monoamine Oxidase ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
The Past ◽  
Structure Activity ◽  
Receptor Interactions ◽  
Heterocyclic Derivatives ◽  
Inhibitory Activities ◽  
Leading Compounds ◽  
Heterocyclic Moiety

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson’s disease and Alzheimer’s disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

Synthetic Strategies, Chemical Reactivities and Biological Activities of 3-Thioxo-1,2,4-Triazin-5-Ones and Their Derivatives

2019 ◽  
Vol 16 (4) ◽  
pp. 308-322
Author(s):  
Mohammad S.T. Makki ◽  
Reda M. Abdel-Rahman ◽  
Abdulrahman S. Alharbi
Keyword(s):  
Biological Activities ◽  
Biological Evaluation ◽  
Literature Survey ◽  
Recent Advances ◽  
Nucleophilic Reagents ◽  
Anti Hiv ◽  
Biological Field

In recent years, a very interest in the synthesis of functionalized 3-thioxo-1,2,4-triazin-5- ones and their derivatives as vital probes has been increased, due to the important, applications of the medicinal, pharmacological, and biological field as a drug, semi drug, and bioactive systems. The present work review outlines extensive recent advances literature survey on the synthesis of sulfurbearing 1,2,4-triazin-5-one derivatives has been reconsidered. Also, the behavior of these family towards electrophilic and nucleophilic reagents in different media and conditions reported. The biological evaluation of the most synthesized systems included anticancer, anti-HIV, antimicrobial as well as their enzymatic effects (cellobiase produced by fungi) have been reported. The reactivity of these systems depends on the polarity of solvent, temperature, molarity as well as a type of tautomeric present.

Synthesis, Biological Evaluation and Molecular Docking Study of Cyclic Diarylheptanoids as Potential Anticancer Therapeutics

2020 ◽  
Vol 20 (4) ◽  
pp. 464-475 ◽  
Author(s):  
Yang Lu ◽  
Wencui Yin ◽  
Mohammad S. Alam ◽  
Adnan A. Kadi ◽  
Yurngdong Jahng ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
In Silico ◽  
Topoisomerase I ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Topoisomerase Iiα ◽  
Inhibitory Activities ◽  
Formed Hydrogen

Background: Cancer is one of the leading causes of mortality globally. To cope with cancer, it is necessary to develop anticancer drugs. Bioactive natural products, i.e. diarylheptanoids, have gained significant attention of researchers owing to their intriguing structures and potent biological activities. In this article, considering the development of anticancer drugs with enhanced selectivity towards cancerous cells, a series of Cyclic Diarylheptanoids (CDHs) are designed, synthesized and evaluated their biological activity. Objective: To establish an easy route for the synthesis of diarylheptanoids, and evaluate their antiproliferative, and topoisomerase-I & -IIα inhibitory activities, for developing potential anticancer drugs among CDHs. Methods: Diarylheptanoids were synthesized from reported linear diarylheptanoids using the classical Ullmann reaction. Antibacterial activity was evaluated by the filter paper disc diffusion method. Cell viability was assessed by measuring mitochondrial dehydrogenase activity with a Cell Counting Kit (CCK-8). Topoisomerases I and II (topo-I and -IIα) inhibitory activity was measured by the assessment of relaxation of supercoiled pBR322 plasmid DNA. IFD protocol of Schrodinger Maestro v11.1 was used to characterize the binding pattern of studied compounds with the ATPase domain of the human topo-IIα. Results: The synthesized CDHs were evaluated for their biological activities (antibacterial, antiproliferative, and topoisomerase-I & -IIα inhibitory activities, respectively). Leading to obtain a series of anticancer agents with the least inhibitory activities against different microbes, improving their selectivity for cancer cells. In brief, most of the synthesized CDHs had excellent antiproliferative activity against T47D (human breast cancer cell line). Pterocarine possessed the strongest activity (2i; IC50 = 0.63µM) against T47D. The cyclic diarylheptanoid 2b induced 30% inhibition of topoisomerase-IIα activity at 100μM compared with the reference of etoposide, which induced 72% inhibition. Among the tested compounds, galeon (2h) displayed very low activity against four bacterial strains. Compounds 2b, 2h, and 2i formed hydrogen bonds with Thr215, Asn91, Asn120, Ala167, Lys168 and Ile141 residues, which are important for binding of ligand compound to the ATPase binding site of topoisomerase IIα by acting as ATP competitive molecule validated by docking study. In silico Absorption, Distribution, Metabolism and Excretion (ADME) analysis revealed the predicted ADME parameters of the studied compounds which showed recommended values. Conclusion: A series of CDHs were synthesized and evaluated for their antibacterial, antiproliferative, and topo-I & -IIα inhibitory activities. SARs study, molecular docking study and in silico ADME analysis were conducted. Five compounds exhibited excellent and selective antiproliferative activity against the human breast cancer cell line (T47D). Among them, a compound 2h showed topo-IIα activity by 30% at 100µM, which represented a moderate intensity of inhibition compared with etoposide. Three of them formed hydrogen bonds with Thr215, Asn91, Asn120, and Ala167 residues, which are considered as crucial residues for binding to the ATPase domain of topoisomerase IIα. According to in silico drug-likeness property analysis, three compounds are expected to show superiority over etoposide in case of absorption, distribution, metabolism and excretion.

scholarly journals C1 Inhibitor Prevents Endotoxin Shock Via a Direct Interaction with Lipopolysaccharide

2003 ◽  
Vol 171 (5) ◽  
pp. 2594-2601 ◽  
Author(s):  
Dongxu Liu ◽  
Shenghe Cai ◽  
Xiaogang Gu ◽  
Jennifer Scafidi ◽  
Xiao Wu ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Endotoxin Shock ◽  
C1 Inhibitor

scholarly journals Biosynthesis, Characterization, and Biological Activities of Procyanidin Capped Silver Nanoparticles

2020 ◽  
Vol 11 (3) ◽  
pp. 66
Author(s):  
Umar M. Badeggi ◽  
Jelili A. Badmus ◽  
Subelia S. Botha ◽  
Enas Ismail ◽  
Jeanine L. Marnewick ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Food Packaging ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Bacterial Species ◽  
Bactericidal Effect ◽  
Total Extract ◽  
Selected Area Electron Diffraction ◽  
Ic50 Values ◽  
Inhibitory Activities

In this study, procyanidin dimers and Leucosidea sericea total extract (LSTE) were employed in the synthesis of silver nanoparticles (AgNPs) and characterized by ultraviolet-visible (UV-Visible) spectroscopy, high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), X-ray diffraction (XRD), and dynamic light scattering (DLS) techniques. AgNPs of about 2–7 nm were obtained. DLS and stability evaluations confirmed that the AgNPs/procyanidins conjugates were stable. The formed nanoparticles exhibited good inhibitory activities against the two enzymes studied. The IC50 values against the amylase enzyme were 14.92 ± 1.0, 13.24 ± 0.2, and 19.13 ± 0.8 µg/mL for AgNPs coordinated with LSTE, F1, and F2, respectively. The corresponding values for the glucosidase enzyme were 21.48 ± 0.9, 18.76 ± 1.0, and 8.75 ± 0.7 µg/mL. The antioxidant activities were comparable to those of the intact fractions. The AgNPs also demonstrated bacterial inhibitory activities against six bacterial species. While the minimum inhibitory concentrations (MIC) of F1-AgNPs against Pseudomonas aeruginosa and Staphylococcus aureus were 31.25 and 15.63 µg/mL respectively, those of LSTE-AgNPs and F2-AgNPs against these organisms were both 62.50 µg/mL. The F1-AgNPs demonstrated a better bactericidal effect and may be useful in food packaging. This research also showed the involvement of the procyanidins as reducing and capping agents in the formation of stable AgNPs with potential biological applications.

The presence of food-derived collagen peptides in human body-structure and biological activity

2017 ◽  
Vol 8 (12) ◽  
pp. 4325-4330 ◽  
Author(s):  
Kenji Sato
Keyword(s):  
Biological Activity ◽  
Human Body ◽  
Biological Activities ◽  
Body Structure ◽  
Collagen Peptides ◽  
Recent Advances

While it was difficult to detect food-derived peptide in blood (A), recent advances enables identify them (B) and examine their biological activities.

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