Classification, Toxicity and Bioactivity of Natural Diterpenoid Alkaloids

Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes and produced primarily from plants in the Aconitum, Delphinium, Consolida genera. Corals, Xenia, Okinawan/Clavularia, Alcyonacea (soft corals) and marine sponges are rich sources of diterpenoids, despite the difficulty to access them and the lack of availability. Researchers have long been concerned with the potential beneficial or harmful effects of diterpenoid alkaloids due to their structural complexity, which accounts for their use as pharmaceuticals as well as their lousy reputation as toxic substances. Compounds belonging to this unique and fascinating family of natural products exhibit a broad spectrum of biological activities. Some of these compounds are on the list of clinical drugs, while others act as incredibly potent neurotoxins. Despite numerous attempts to prepare synthetic products, this review only introduces the natural diterpenoid alkaloids, describing 'compounds' structures and classifications and their toxicity and bioactivity. The purpose of the review is to highlight some existing relationships between the presence of substituents in the structure of such molecules and their recognized bioactivity

Synthesis and Characterization of Designed Guaifenesin Prodrugs

Guaifenesin is an extremely bitter taste substance which affects its usage in pediatric and geriatric formulations. In this thesis we aimed to mask the bitter taste of guaifenesin by converting it to a potential tasteless prodrugs using different linkers. The prodrugs were synthesized by esterification of carboxylic acid anhydrides and guaifenesin. Maleic anhydride, succinic anhydride, and glutaric anhydride, respectively, were used to synthesize guaifenesin ester prodrugs (guaifenesin maleate, guaifenesin succinate, guaifenesin glutarate), 1 H-NMR, LC-MS, and FT-IR have confirmed the identity and purity of the new prodrugs. In vitro kinetic studies for the above mentioned prodrugs were done in four different aqueous media: 1 N HCl and buffers pH 3.3, pH 5.5 and pH 7.4. Under the experimental conditions the target prodrug was hydrolyzed to release the parent drug, guaifenesin, as was confirmed by HPLC determination. The kobs and the corresponding t1/2 values for guaifenesin prodrugs in 1N HCl were calculated from the linear regression equation correlating the log concentration of the prodrug versus time. The rate constant (kobs) was found to be 7.2x10-4 for guaifenesin maleate prodrug, 2.54x10-4 guaifenesin succinate prodrug, and 2.36x10-4 guaifenesin glutarate prodrug. Half-lives values (t1/2) were 2.01 hours for guaifenesin maleate prodrug, 7.03 hours for guaifenesin succinate prodrugs, and 7.17 hours for guaifenesin glutarate prodrug. On the other hand, at pH 3.3, 5.5 and 7.4, guaifenesin maleate, guaifenesin succinate, and guaifenesin glutarate prodrugs were entirely stable and no release of the parent drug, guaifenesin, was observed

Anti-cancer Prodrugs-Three Decades of Design

The conventional old treatment method for cancer therapy is associated with severe side effects along with several limitations. Therefore, searching and developing new methods for cancer became crucial. This mini review was devoted on the design and synthesis of prodrugs for cancer treatment. The methods discussed include targeted prodrugs which are depending on the presence of unique cellular conditions at the desired target, especially the availability of certain enzymes and transporters at these target sites, antibody directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) which is considered one of the important strategies for the treatment of cancer and prodrugs based on enzyme models that have been advocated to understand enzyme catalysis. In this approach, a design of prodrugs is accomplished using computational calculations based on molecular orbital and molecular mechanics methods. Correlations between experimental and calculated rate values for some intramolecular processes provided a tool to predict thermodynamic and kinetic parameters for intramolecular processes that can be utilized as prodrugs linkers. This approach does not require any enzyme to catalyze the prodrug interconversion. The interconversion rate is solely dependent on the factors govern the limiting step of the intramolecular process

The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens

The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many scientists are conducting research on plants aiming to discover possible antimicrobial compounds. The secondary metabolites contained in plants are a source of chemical entities having pharmacological activities and intended to be used for the treatment of different diseases. These chemical entities have the potential to be used as an effective antioxidant, antimutagenic, anticarcinogenic and antimicrobial agents. Among these pharmacologically active entities are the alkaloids which are classified into a number of classes, including pyrrolizidines, pyrrolidines, quinolizidines, indoles, tropanes, piperidines, purines, imidazoles, and isoquinolines. Alkaloids that have antioxidant properties are capable of preventing a variety of degenerative diseases through capturing free radicals, or through binding to catalysts involved indifferent oxidation processes occurring within the human body. Furthermore, these entities are capable of inhibiting the activity of bacteria, fungi, protozoan and etc. The unique properties of these secondary metabolites are the main reason for their utilization by the pharmaceutical companies for the treatment of different diseases. Generally, these alkaloids are extracted from plants, animals and fungi. Penicillin is the most famous natural drug discovery deriving from fungus. Similarly, marines have been used as a source for thousands of bioactive marine natural products. In this review, we cover the medical use of natural alkaloids isolated from a variety of plants and utilized by humans as antibacterial, antiviral, antifungal and anticancer agents. An example for such alkaloids is berberine, an isoquinoline alkaloid, found in roots and stem-bark of Berberis asculin P. Renault plant and used to kill a variety of microorganisms

The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens

The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many scientists are conducting research on plants aiming to discover possible antimicrobial compounds. The secondary metabolites contained in plants are a source of chemical entities having pharmacological activities and intended to be used for the treatment of di erent diseases. These chemical entities have the potential to be used as an e ective antioxidant, antimutagenic, anticarcinogenic and antimicrobial agents. Among these pharmacologically active entities are the alkaloids which are classified into a number of classes, including pyrrolizidines, pyrrolidines, quinolizidines, indoles, tropanes, piperidines, purines, imidazoles, and isoquinolines. Alkaloids that have antioxidant properties are capable of preventing a variety of degenerative diseases through capturing free radicals, or through binding to catalysts involved indi erent oxidation processes occurring within the human body. Furthermore, these entities are capable of inhibiting the activity of bacteria, fungi, protozoan and etc. The unique properties of these secondary metabolites are the main reason for their utilization by the pharmaceutical companies for the treatment of di erent diseases. Generally, these alkaloids are extracted from plants, animals and fungi. Penicillin is the most famous natural drug discovery deriving from fungus. Similarly, marines have been used as a source for thousands of bioactive marine natural products. In this review, we cover the medical use of natural alkaloids isolated from a variety of plants and utilized by humans as antibacterial, antiviral, antifungal and anticancer agents. An example for such alkaloids is berberine, an isoquinoline alkaloid, found in roots and stem-bark of Berberis asculin P. Renault plant and used to kill a variety of microorganisms.Funding: This research received no external funding. Acknowledgments: Authors are thankful to Basilicata University for supporting the present study

Diclofenac Codrugs and Prodrugs-Three Decades of Design

Prodrugs or predrugs are inactive molecules which become active after in vivo conversion to release the active parent drug. The prodrug’s cleavage can be catalyzed by metabolic enzymes or can occur by chemical means without the involvement of enzymes. Prodrugs are designed to improve undesirable physicochemical and pharmacokinetic properties of their parent drugs. Non-steroidal anti-inflammatory (NSAIDs) drugs are among the most commonly used drugs for treatment of pain, inflammation and fever. Despite their frequent use, these agents suffer from gastrointestinal side effects that limit their use for those patients with gastrointestinal conditions. This mini review discusses the design, synthesis and pharmacological effects of prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs) Diclofenac sodium or potassium. It argues that the prodrug approach has the potential to eliminate Diclofenac associated gastrointestinal complications, increases its bioavailability and masks its bitter taste

Antifungal and Antibacterial Activities of Isolated Marine Compounds

To combat the ineffectiveness of currently available pharmaceutical medications, caused by the emergence of increasingly resistant bacterial and fungal strains, novel antibacterial and antifungal medications are urgently needed. Novel natural compounds with antimicrobial activities can be obtained by exploring underexplored habitats such as the world’s oceans. The oceans represent the largest ecosystem on earth, with a high diversity of organisms. Oceans have received some attention in the past few years, and promising compounds with antimicrobial activities were isolated from marine organisms such as bacteria, fungi, algae, sea cucumbers, sea sponges, etc. This review covers 56 antifungal and 40 antibacterial compounds from marine organisms. These compounds are categorized according to their chemical structure groups, including polyketides, alkaloids, ribosomal peptides, and terpenes, and their organismal origin. The review provides the minimum inhibitory concentration MIC values and the bacterial/fungal strains against which these chemical compounds show activity. This study shows strong potential for witnessing the development of new novel antimicrobial drugs from these natural compounds isolated and evaluated for their antimicrobial activities

Understanding the Risks of Diffusion of Cyanobacteria Toxins in Rivers, Lakes, and Potable Water

Blue-green algae, or cyanobacteria, may be prevalent in our rivers and tap water. These minuscule bacteria can grow swiftly and form blooms in warm, nutrient-rich water. Toxins produced by cyanobacteria can pollute rivers and streams and harm the liver and nervous system in humans. This review highlights the properties of 25 toxin types produced by 12 different cyanobacteria genera. The review also covered strategies for reducing and controlling cyanobacteria issues. These include using physical or chemical treatments, cutting back on fertilizer input, algal lawn scrubbers, and antagonistic microorganisms for biocontrol. Micro-, nano- and ultrafiltration techniques could be used for the removal of internal and extracellular cyanotoxins, in addition to powdered or granular activated carbon, ozonation, sedimentation, ultraviolet radiation, potassium permanganate, free chlorine, and pre-treatment oxidation techniques. The efficiency of treatment techniques for removing intracellular and extracellular cyanotoxins is also demonstrated. These approaches aim to lessen the risks of cyanobacterial blooms and associated toxins. Effective management of cyanobacteria in water systems depends on early detection and quick action. Cyanobacteria cells and their toxins can be detected using microscopy, molecular methods, chromatography, and spectroscopy. Understanding the causes of blooms and the many ways for their detection and elimination will help the management of this crucial environmental issue

ANTICANCER PRODRUGS - THREE DECADES OF DESIGN

The conventional old treatment method for cancer therapy is associated with severe side effects along with several limitations. Therefore, searching and developing new methods for cancer became crucial. This mini review was devoted on the design and synthesis of prodrugs for cancer treatment. The methods discussed include targeted prodrugs which are depending on the presence of unique cellular conditions at the desired target, especially the availability of certain enzymes and transporters at these target sites, antibody directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) which is considered one of the important strategies for the treatment of cancer and prodrugs based on enzyme models that have been advocated to understand enzyme catalysis. In this approach, a design of prodrugs is accomplished using computational calculations based on molecular orbital and molecular mechanics methods. Correlations between experimental and calculated rate values for some intramolecular processes provided a tool to predict thermodynamic and kinetic parameters for intramolecular processes that can be utilized as prodrugs linkers. This approach does not require any enzyme to catalyze the prodrug interconversion. The interconversion rate is solely dependent on the factors govern the limiting step of the intramolecular process