Mechanisms of action of naturally occurring irreversible enzyme inhibitors

1975 ◽  
Vol 8 (8) ◽  
pp. 281-288 ◽  
Author(s):  
Robert R. Rando
Keyword(s):  
Enzyme Inhibitors ◽  
Mechanisms Of Action ◽  
Naturally Occurring

scholarly journals Interruption of tumor-associated platelet consumption with platelet enzyme inhibitors

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1252-1258 ◽  
Author(s):  
SJ Slichter ◽  
PL Weiden ◽  
MR O'Donnell ◽  
R Storb
Keyword(s):  
Synergistic Effect ◽  
Enzyme Inhibitors ◽  
Enzyme Inhibitor ◽  
Phosphodiesterase Inhibitor ◽  
Metastatic Tumor ◽  
Mechanisms Of Action ◽  
Cyclooxygenase Inhibitor ◽  
Normal Platelet ◽  
Naturally Occurring ◽  
Platelet Survival

Abstract Twenty dogs with naturally occurring metastatic tumors were treated with anticoagulants (Warfarin) or platelet enzyme inhibitor drugs (dipyridamole, dipyridamole plus aspirin, RA233, sulfinpyrazone, or a combination of RA233 and sulfinpyrazone) to determine if tumor-related reductions in platelet survival and concentration could be reversed. Anticoagulation was ineffective, while platelet enzyme inhibitors were able to produce improvements in platelet survival. Of the 18 dogs with metastatic tumor treated with platelet enzyme inhibitors, only 5 (28%) showed a reduction in platelet survival during the first week of observation on therapy compared to their baseline survivals. This is significantly different than the decreases in platelet survivals observed in 8 of 10 untreated dogs (80%) with metastatic tumor observed for the same interval. Furthermore, 8 of the 18 treated dogs (44%) had platelet survivals within 2 standard deviations of normal, compared to only 1 of 10 untreated dogs. Of the 8 dogs with normal platelet survivals, 6 were treated with a combination of a phosphodiesterase inhibitor (RA233 or dipyridamole) and a cyclooxygenase inhibitor (sulfinpyrazone or aspirin). The combination of RA233 and sulfinpyrazone was the best drug program tested and resulted in normal platelet survivals in 63% and improved platelet counts in 75% of the animals treated. Thus, platelet enzyme inhibitors with different mechanisms of action may have a synergistic effect in reversing the abnormal platelet hemostasis found in a variety of spontaneously occurring canine neoplasms.

scholarly journals Interruption of tumor-associated platelet consumption with platelet enzyme inhibitors

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1252-1258
Author(s):  
SJ Slichter ◽  
PL Weiden ◽  
MR O'Donnell ◽  
R Storb
Keyword(s):  
Synergistic Effect ◽  
Enzyme Inhibitors ◽  
Enzyme Inhibitor ◽  
Phosphodiesterase Inhibitor ◽  
Metastatic Tumor ◽  
Mechanisms Of Action ◽  
Cyclooxygenase Inhibitor ◽  
Normal Platelet ◽  
Naturally Occurring ◽  
Platelet Survival

Twenty dogs with naturally occurring metastatic tumors were treated with anticoagulants (Warfarin) or platelet enzyme inhibitor drugs (dipyridamole, dipyridamole plus aspirin, RA233, sulfinpyrazone, or a combination of RA233 and sulfinpyrazone) to determine if tumor-related reductions in platelet survival and concentration could be reversed. Anticoagulation was ineffective, while platelet enzyme inhibitors were able to produce improvements in platelet survival. Of the 18 dogs with metastatic tumor treated with platelet enzyme inhibitors, only 5 (28%) showed a reduction in platelet survival during the first week of observation on therapy compared to their baseline survivals. This is significantly different than the decreases in platelet survivals observed in 8 of 10 untreated dogs (80%) with metastatic tumor observed for the same interval. Furthermore, 8 of the 18 treated dogs (44%) had platelet survivals within 2 standard deviations of normal, compared to only 1 of 10 untreated dogs. Of the 8 dogs with normal platelet survivals, 6 were treated with a combination of a phosphodiesterase inhibitor (RA233 or dipyridamole) and a cyclooxygenase inhibitor (sulfinpyrazone or aspirin). The combination of RA233 and sulfinpyrazone was the best drug program tested and resulted in normal platelet survivals in 63% and improved platelet counts in 75% of the animals treated. Thus, platelet enzyme inhibitors with different mechanisms of action may have a synergistic effect in reversing the abnormal platelet hemostasis found in a variety of spontaneously occurring canine neoplasms.

Advancement of Natural Compounds as Anti- Rheumatoid Arthritis Agents: Focus on Their Mechanism of Actions

2021 ◽  
Vol 21 ◽  
Author(s):  
Huanghe Yu ◽  
Yixing Qiu ◽  
Shumaila Tasneem ◽  
Muhammad Daniyal ◽  
Bin Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Bone Destruction ◽  
Inflammatory Cells ◽  
Chronic Inflammatory Disease ◽  
Mechanisms Of Action ◽  
Pannus Formation ◽  
Synovial Hyperplasia ◽  
Naturally Occurring ◽  
Natural Plants

: Rheumatoid arthritis (RA) is a chronic inflammatory disease categorized by infiltration of inflammatory cells, synovial hyperplasia, pannus formation and bone destruction, leading to disability worldwide. Despite the presence of the commercial availability of anti-RA agent on the market, the application of these drugs is limited due to its side effects. Anti-rheumatic drugs are more effective and safer being investigated by many researchers, especially, natural products with anti-RA have been identified and the underlying molecular mechanisms of action of novel and known compounds have been reported. In this review, we intend to provide a comprehensive view and updated on naturally occurring compounds known and novel that has the effect of anti-RA, and then classify them according to their molecular mechanisms of action in regulating the anti-RA lane main. The safety of compounds from natural plants and western medicine has also been briefly compared. In addition, the clinical trials with anti-RA compounds isolated from natural plants in RA were also summarized in this manuscript.

scholarly journals Snake Venom: Any Clue for Antibiotics and CAM?

2005 ◽  
Vol 2 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Deivy Clementino de Lima ◽  
Paula Alvarez Abreu ◽  
Cícero Carlos de Freitas ◽  
Dilvani Oliveira Santos ◽  
Rodrigo Oliveira Borges ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Alternative Medicine ◽  
Complementary And Alternative Medicine ◽  
Snake Venom ◽  
Biological Effects ◽  
Mechanisms Of Action ◽  
Snake Venoms ◽  
Commercial Use ◽  
Naturally Occurring ◽  
Complementary And Alternative

Lately several naturally occurring peptides presenting antimicrobial activity have been described in the literature. However, snake venoms, which are an enormous source of peptides, have not been fully explored for searching such molecules. The aim of this work is to review the basis of antimicrobial mechanisms revealing snake venom as a feasible source for searching an antibiotic prototype. Therefore, it includes (i) a description of the constituents of the snake venoms involved in their main biological effects during the envenomation process; (ii) examples of snake venom molecules of commercial use; (iii) mechanisms of action of known antibiotics; and (iv) how the microorganisms can be resistant to antibiotics. This review also shows that snake venoms are not totally unexplored sources for antibiotics and complementary and alternative medicine (CAM).

Properties and mechanisms of action of naturally occurring antifungal peptides

2013 ◽  
Vol 70 (19) ◽  
pp. 3545-3570 ◽  
Author(s):  
Nicole L. van der Weerden ◽  
Mark R. Bleackley ◽  
Marilyn A. Anderson
Keyword(s):  
Mechanisms Of Action ◽  
Naturally Occurring ◽  
Antifungal Peptides

scholarly journals Imaging the Antistaphylococcal Activity of CATH-2: Mechanism of Attack and Regulation of Inflammatory Response

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Viktoria A. F. Schneider ◽  
Maarten Coorens ◽  
Johanna L. M. Tjeerdsma-van Bokhoven ◽  
George Posthuma ◽  
Albert van Dijk ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Immune Activation ◽  
Live Imaging ◽  
Mechanisms Of Action ◽  
Bacterial Membrane ◽  
Methicillin Resistant ◽  
Content Type ◽  
Naturally Occurring ◽  
Novel Approach ◽  
Near Future

ABSTRACT Due to the high use of antibiotics in both human and veterinary settings, many bacteria have become resistant to those antibiotics that we so heavily rely on. Methicillin-resistant S. aureus (MRSA) is one of these difficult-to-treat resistant pathogens for which novel antimicrobial therapies will be required in the near future. One novel approach could be the utilization of naturally occurring antimicrobial peptides, such as chicken CATH-2, which have been show to act against a wide variety of bacteria. However, before these peptides can be used clinically, more knowledge of their functions and mechanisms of action is required. In this study, we used live imaging and electron microscopy to visualize in detail how CATH-2 kills S. aureus, and we investigated how CATH-2 affects immune activation by S. aureus. Together, these results give a better understanding of how CATH-2 kills S. aureus and what the potential immunological consequences of this killing can be. Chicken cathelicidin-2 (CATH-2) is a broad-spectrum antimicrobial host defense peptide (HDP) that may serve as a paradigm for the development of new antimicrobial agents. While previous studies have elucidated the mechanism by which CATH-2 kills Escherichia coli, its mode of action against Gram-positive bacteria remains to be determined. In this study, we explored the underlying antibacterial mechanism of CATH-2 against a methicillin-resistant strain of Staphylococcus aureus and the effect of CATH-2-mediated S. aureus killing on immune activation. Visualization of the antimicrobial activity of CATH-2 against S. aureus with live-imaging confocal microscopy demonstrated that CATH-2 directly binds the bacteria, which is followed by membrane permeabilization and cell shrinkage. Transmission electron microscopy (TEM) studies further showed that CATH-2 initiated pronounced morphological changes of the membrane (mesosome formation) and ribosomal structures (clustering) in a dose-dependent manner. Immunolabeling of these sections demonstrated that CATH-2 binds and passes the bacterial membrane at subminimal bactericidal concentrations (sub-MBCs). Furthermore, competition assays and isothermal titration calorimetry (ITC) analysis provided evidence that CATH-2 directly interacts with lipoteichoic acid and cardiolipin. Finally, stimulation of macrophages with S. aureus and CATH-2 showed that CATH-2 not only kills S. aureus but also has the potential to limit S. aureus-induced inflammation at or above the MBC. Taken together, it is concluded that at sub-MBCs, CATH-2 perturbs the bacterial membrane and subsequently enters the cell and binds intracellular S. aureus components, while at or above the MBC, CATH-2 causes disruption of membrane integrity and inhibits S. aureus-induced macrophage activation. IMPORTANCE Due to the high use of antibiotics in both human and veterinary settings, many bacteria have become resistant to those antibiotics that we so heavily rely on. Methicillin-resistant S. aureus (MRSA) is one of these difficult-to-treat resistant pathogens for which novel antimicrobial therapies will be required in the near future. One novel approach could be the utilization of naturally occurring antimicrobial peptides, such as chicken CATH-2, which have been show to act against a wide variety of bacteria. However, before these peptides can be used clinically, more knowledge of their functions and mechanisms of action is required. In this study, we used live imaging and electron microscopy to visualize in detail how CATH-2 kills S. aureus, and we investigated how CATH-2 affects immune activation by S. aureus. Together, these results give a better understanding of how CATH-2 kills S. aureus and what the potential immunological consequences of this killing can be.

Naturally occurring enzyme inhibitors and their pharmaceutical applications

2011 ◽  
Vol 83 (9) ◽  
pp. 1741-1749 ◽  
Author(s):  
Athar Ata ◽  
Samina Naz ◽  
Evan M. Elias
Keyword(s):  
Enzyme Inhibitors ◽  
Senile Dementia ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Ache Inhibitors ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Antiparasitic Drug

Enzyme inhibitors play a significant role in the drug discovery process. For instance, acetylcholinesterase (AChE) inhibitors have applications in curing Alzheimer’s disease (AD), senile dementia, ataxia, myasthenia gravis, and Parkinson’s disease. Glutathione S-transferase (GST) inhibitors have applications as adjuvants to overcome anticancer and antiparasitic drug resistance problems. Compounds inhibiting the activity of α-glucosidase are used to treat type 2 diabetes mellitus and obesity problems. This article describes the identification of natural products exhibiting AChE, GST, and α-glucosidase inhibitory activities from medicinally important plants. Additionally, structure–activity relationship (SAR) studies of these newly discovered enzyme inhibitors are also discussed.

scholarly journals GenusCaulophyllum: An Overview of Chemistry and Bioactivity

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Yong-Gang Xia ◽  
Guo-Yu Li ◽  
Jun Liang ◽  
Bing-You Yang ◽  
Shao-Wa Lü ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Membrane ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Pharmacological Properties ◽  
Cell Membrane Chromatography ◽  
Action Mechanisms ◽  
Naturally Occurring ◽  
Activity Screening ◽  
Point Of Reference

Recently, some promising advances have been achieved in understanding the chemistry, pharmacology, and action mechanisms of constituents from genusCaulophyllum. Despite this, there is to date no systematic review of those of genusCaulophyllum. This review covers naturally occurring alkaloids and saponins and those resulting from synthetic novel taspine derivatives. The paper further discussed several aspects of this genus, including pharmacological properties, mechanisms of action, pharmacokinetics, and cell membrane chromatography for activity screening. The aim of this paper is to provide a point of reference for pharmaceutical researchers to develop new drugs from constituents ofCaulophyllumplants.

scholarly journals A REVIEW OF BENZOPYRAN DERIVATIVES IN PHARMACOTHERAPY OF BREAST CANCER

2018 ◽  
Vol 11 (7) ◽  
pp. 43 ◽  
Author(s):  
Kumar Piyush ◽  
Singh Kuldeep ◽  
Rahman Md. Azizur ◽  
Hasan Syed Misbahul ◽  
Wal Pranay
Keyword(s):  
Breast Cancer ◽  
Natural Products ◽  
Biological Effects ◽  
Mechanisms Of Action ◽  
Ring System ◽  
Pharmacological Properties ◽  
Substitution Pattern ◽  
Naturally Occurring ◽  
Anti Hiv ◽  
Cancer Activity

One of the naturally occurring compounds containing oxygen moiety is benzopyran. Depending on its substitution pattern, different biological effects are shown. The benzopyran ring system is present in many natural products (such as genistein, hesperidin, and warfarin) as well as synthetic products. It displays pharmacological properties such as antitumor, anti-HIV, antimicrobials, anti-inflammatory, and anticoagulants. The sufficient literature support and the fact that benzopyran has potential as a pharmacophore particularly as anti-breast cancer, etc, current research seemed pertinent keeping in view the mechanism of anti-breast cancer activity. Therefore, the objective of this review is to focus on important benzopyran analogs with anti-breast cancer activity and highlight their mechanisms of action.

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