scholarly journals Biological activity of the growth factor-induced cytokine N51: structure-function analysis using N51/Interleukin-8 chimeric molecules.

1994 ◽  
Vol 14 (5) ◽  
pp. 2849-2861 ◽  
Author(s):  
J N Heinrich ◽  
E C O'Rourke ◽  
L Chen ◽  
H Gray ◽  
K S Dorfman ◽  
...  
Keyword(s):  
Biological Activity ◽  
Function Analysis ◽  
Specific Binding ◽  
Biological Activities ◽  
Interleukin 8 ◽  
Early Gene ◽  
Human Neutrophils ◽  
Apparent Homogeneity ◽  
C Terminus ◽  
Hybrid Molecules

The immediate-early gene N51/KC encodes a protein which following expression in the baculovirus system and purification to apparent homogeneity is able to induce chemotaxis and intracellular Ca2+ flux, to compete for 125I-labeled interleukin-8 (IL-8) binding, and upon iodination, to bind specifically to human neutrophils. The activity of N51/KC can be distinguished from that of IL-8 by a number of criteria. First, at equivalent concentrations, the specific binding of [125I]N51/KC to human neutrophils is about 10 times less than that of [125I]IL-8. Second, the competition studies of [125I]IL-8 with IL-8 define a single class of high-affinity receptors, while the presence of both a high- and a low-affinity class of receptors is defined by N51/KC. Third, although the changes in intracellular Ca2+ of fura-2/AM-preloaded human neutrophils elicited by N51/KC and IL-8 are similar, pretreatment of the cells with N51/KC did not result in a loss of response to a subsequent treatment with IL-8; in contrast, treatment with IL-8 did result in the subsequent desensitization to N51/KC. To further characterize N51/KC, mutants and hybrids of N51/KC and IL-8 were produced and analyzed for the ability to compete for [125I]IL-8 binding and elicit intracellular Ca2+ changes in human neutrophils. Two important observations came from these studies. First, the N51/IL-8I hybrid in which the N51/KC sequence between cysteines 2 and 3 (or first disulfide bond) is replaced by the corresponding sequence in IL-8 shows IL-8-like properties, indicating that this region is important for specific receptor recognition. Second, the N51 delta III and IL-8 delta III C-terminus deletion mutants were biologically inactive, but the hybrid molecules N51/IL-8III and IL-8/N51III, in which the C termini were exchanged, had biological activities similar to that of the wild-type molecules, demonstrating that the presence of the C terminus is essential for the biological activity of these chemokines but does not confer receptor specificity.

Progress and development of C-3, C-6, and N-9 position substituted carbazole integrated molecular hybrid molecules as potential anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Pratibha Mehta Luthra ◽  
Nitin Kumar
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Structural Motif ◽  
Hybrid Compounds ◽  
Hybrid Molecules ◽  
Anticancer Mechanism ◽  
Pharmacologically Active

Abstract: The carbazole skeleton, a key structural motif occurring naturally or chemically synthesized, have shown various biological activities. Molecular hybridization based on the combination of two or more bioactive pharmacophores has been an important tool to convert the potent structural leads to form new hybrid compounds with improved biological activity. In recent years, modifications/substitutions of the carbazole motif at C3, C6, N9 position have been carried to develop novel carbazole based potential anticancer agents in the cancer therapy. In the last fifteen years, several compounds based on carbazole core integrated to pharmacologically active molecular hybrid having active pharmacophore such as 1,3,4-thiadiazole, thiazole, guanidine, sulfonamides, glyoxamides, imidazole, phenanthrene, rhodamine, chalcones, imidazopyridine, platinum 2H-chromen-2-one, hydrazones, piperazine, Isoxazole-thiadiazole, pyrazole etc. have been synthesized showing anticancer profile at sub-micromolar to nano-molar concentrations. We have thoroughly reviewed the design, progress and development of C-3, C-6, and N-9 position substituted carbazole derivatives integrated with various medicinally active pharmacophore as potential anticancer agents evaluated against various cancer cell lines. Additionally, the anticancer mechanism and in vivo activity of the reported compounds have been discussed. This study will support in designing of a new pharmacophore that can be linked to carbazole motif for development for new, potent and target specific anticancer drugs with improved pharmacokinetics and minimal side effects.

The Inhibitory Effect of Heparin and Related Glycosaminoglycans on Neutrophil Chemotaxis

1984 ◽  
Vol 52 (02) ◽  
pp. 134-137 ◽  
Author(s):  
Yaacov Matzner ◽  
Gerard Marx ◽  
Ruth Drexler ◽  
Amiram Eldor
Keyword(s):  
Specific Binding ◽  
Anticoagulant Activity ◽  
Neutrophil Migration ◽  
Inhibitory Effect ◽  
Chemotactic Factor ◽  
Human Neutrophils ◽  
Boyden Chamber ◽  
Neutrophil Chemotaxis ◽  
Inhibitory Effects ◽  
Chemotactic Factors

SummaryClinical observations have shown that heparin has antiinflammatory activities. The effect of heparin on neutrophil chemotaxis was evaluated in vitro in the Boyden Chamber. This method enabled differentiation between the direct effects of heparin on neutrophil migration and locomotion, and its effects on chemotactic factors. Heparin inhibited both the random migration and directed locomotion of human neutrophils toward zymosan-activated serum (ZAS) and F-met-leu-phe (FMLP). Inhibition was found to be dependent on the concentrations of the heparin and of the chemotactic factors. No specific binding of heparin to the neutrophils could be demonstrated, and heparin’s inhibitory effects were eliminated by simple washing of the cells. When added directly to the chamber containing chemotactic factor, heparin inhibited the chemotactic activity of ZAS but not that of FMLP, suggesting a direct inhibitory effect against C5a, the principal chemotactic factor in ZAS.Experiments performed with low-molecular-weight heparin, N-desulfated heparin, dextran sulfate, chondroitin sulfate and dextran indicated that the inhibitory effects of heparin on neutrophil chemotaxis are not related to its anticoagulant activity, but probably depend on the degree of sulfation of the heparin molecule.

Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential

2018 ◽  
Vol 25 (14) ◽  
pp. 1663-1681 ◽  
Author(s):  
Chun-Ting Lee ◽  
Heng-Chun Kuo ◽  
Yung-Hsiang Chen ◽  
Ming-Yen Tsai
Keyword(s):  
Biological Activity ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Biological Effects ◽  
Herbal Medicines ◽  
Research Field ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
The Family ◽  
Anti Tumor Activity

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.

Naphthoquinone Derivatives Isolated from Plants: Recent Advances in Biological Activity

2020 ◽  
Vol 20 (19) ◽  
pp. 2019-2035
Author(s):  
Esmaeil Sheikh Ahmadi ◽  
Amir Tajbakhsh ◽  
Milad Iranshahy ◽  
Javad Asili ◽  
Nadine Kretschmer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Biological Activity ◽  
Small Molecules ◽  
Anticancer Activity ◽  
Clinical Significance ◽  
Phase Ii ◽  
Biological Activities ◽  
Phase Ii Clinical Trials ◽  
Naturally Occurring ◽  
The Subject

Naturally occurring naphthoquinones (NQs) comprising highly reactive small molecules are the subject of increasing attention due to their promising biological activities such as antioxidant, antimicrobial, apoptosis-inducing activities, and especially anticancer activity. Lapachol, lapachone, and napabucasin belong to the NQs and are in phase II clinical trials for the treatment of many cancers. This review aims to provide a comprehensive and updated overview on the biological activities of several new NQs isolated from different species of plants reported from January 2013 to January 2020, their potential therapeutic applications and their clinical significance.

Synthesis and Biological Activity of Hydrazones and Derivatives: A Review

2020 ◽  
Vol 20 (5) ◽  
pp. 342-368 ◽  
Author(s):  
Juliana de Oliveira Carneiro Brum ◽  
Tanos Celmar Costa França ◽  
Steven R. LaPlante ◽  
José Daniel Figueroa Villar
Keyword(s):  
Biological Activity ◽  
Medicinal Chemistry ◽  
Biological Activities ◽  
New Drugs ◽  
New Drug ◽  
Cancer Inflammation

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer’s, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.

An Overview on Steroids and Microwave Energy in Multi-Component Reactions towards the Synthesis of Novel Hybrid Molecules

2020 ◽  
Vol 17 (8) ◽  
pp. 594-609
Author(s):  
Preetismita Borah ◽  
Vhatkar Dattatraya Shivling ◽  
Bimal Krishna Banik ◽  
Biswa Mohan Sahoo
Keyword(s):  
Energy Consumption ◽  
Multicomponent Reactions ◽  
Biological Activities ◽  
Vital Role ◽  
Microwave Energy ◽  
Biosynthetic Pathways ◽  
Chemical Transformations ◽  
Carbon Carbon Bond ◽  
Hybrid Molecules ◽  
Time Required

In recent years, hybrid systems are gaining considerable attention owing to their various biological applications in drug development. Generally, hybrid molecules are constructed from different molecular entities to generate a new functional molecule with improved biological activities. There already exist a large number of naturally occurring hybrid molecules based on both non-steroid and steroid frameworks synthesized by nature through mixed biosynthetic pathways such as, a) integration of the different biosynthetic pathways or b) Carbon- Carbon bond formation between different components derived through different biosynthetic pathways. Multicomponent reactions are a great way to generate efficient libraries of hybrid compounds with high diversity. Throughout the scientific history, the most common factors developing technologies are less energy consumption and avoiding the use of hazardous reagents. In this case, microwave energy plays a vital role in chemical transformations since it involves two very essential criteria of synthesis, minimizing energy consumption required for heating and time required for the reaction. This review summarizes the use of microwave energy in the synthesis of steroidal and non-steroidal hybrid molecules and the use of multicomponent reactions.

Hybrids of Coumarin Derivatives as Potent and Multifunctional Bioactive Agents: A Review

2020 ◽  
Vol 16 (3) ◽  
pp. 272-306
Author(s):  
Ioannis Fotopoulos ◽  
Dimitra Hadjipavlou-Litina
Keyword(s):  
Pharmacological Activity ◽  
Biological Activities ◽  
Structural Characteristics ◽  
Pharmacokinetic Profile ◽  
Biologically Active ◽  
Hybridization Technique ◽  
Coumarin Derivatives ◽  
Hybrid Molecules ◽  
Pharmacokinetic Properties ◽  
Bioactive Agents

Background: Coumarins exhibit a plethora of biological activities, e.g. antiinflammatory and anti-tumor. Molecular hybridization technique has been implemented in the design of novel coumarin hybrids with several bioactive groups in order to obtain molecules with better pharmacological activity and improved pharmacokinetic profile. Objective: Therefore, we tried to gather as many as possible biologically active coumarin hybrids referred in the literature till now, to delineate the structural characteristics in relation to the activities and to have a survey that might help the medicinal chemists to design new coumarin hybrids with drug-likeness and varied bioactivities. Results: The biological activities of the hybrids in most of the cases were found to be different from the biological activities presented by the parent coumarins. The results showed that the hybrid molecules are more potent compared to the standard drugs used in the evaluation experiments. Conclusion: Conjugation of coumarin with varied pharmacophore groups/druglike molecules responsible for different biological activities led to many novel hybrid molecules, with a multitarget behavior and improved pharmacokinetic properties.

Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

2020 ◽  
Vol 16 ◽  
Author(s):  
Shola Elijah Adeniji
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Biological Activities ◽  
Docking Simulation ◽  
Dna Gyrase ◽  
Computational Design ◽  
Multi Drug Resistance ◽  
Drug Candidate ◽  
Standard Drug

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

scholarly journals Interaction mechanism of aloe-emodin with trypsin: molecular structure–affinity relationship and effect on biological activities

RSC Advances ◽  
2020 ◽  
Vol 10 (35) ◽  
pp. 20862-20871
Author(s):  
Guoyan Ren ◽  
He Sun ◽  
Gen Li ◽  
Jinling Fan ◽  
Lin Du ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Biological Activity ◽  
Biological Activities ◽  
Interaction Mechanism ◽  
Mechanism Of Interaction ◽  
Development And Utilization ◽  
Aloe Emodin

The mechanism of interaction between AE and trypsin was studied firstly. The biological activity of both decreased after the interaction. These results provide a basis for the development and utilization of AE.

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