Antibacterial Activity of Novel Prodrugs of Amoxicillin and Cephalexin

Two novel prodrugs of amoxicillin and cephalexin (amoxicillin ProD 1 and cephalexin ProD 1, respectively) were designed and synthesized to improve the stability and bitter sensation of their parent drugs. The in vitro susceptibility for both prodrugs was determined against Escherichia coli, staphylococcus epidermidis, staphylococcus aureus, Klebsiella pneumonia, streptococcus group A and streptococcus group B, and was compared to that of their active parent drugs.The antibacterial screening demonstrates that amoxicillin ProD 1 and cephalexin ProD 1 were found to be active and are considered among a small number of prodrugs that have therapeutic activity themselves before undergoing interconversion via enzymatic or chemical reaction to their corresponding active parent drugs. Both prodrugs exhibit their antibacterial activity against different types of bacterial strains due to the presence of β- lactam ring in their structures. In addition, it is expected that these novel prodrugs will be much more stable in aqueous media than their corresponding active parent drugs due to the fact that the chemically sensitive amine group contained in the active parent drug structures is replaced with an amide, more chemically stable group, in the corresponding prodrugs

Kamus Bahasa Indonesia-Kulawi

This review supplies the reader with a detailed overview on the utilization of intramolecular processes for a design and synthesis of prodrugs. It is well known that a respected number of drugs suffer from low bioavailability, toxicity, unpleasant taste and presystemic first-pass metabolism which result in drug inactivation. The classical prodrug approach in which the linkage attaching the parent drug to its non-toxic linker and cleaved by in vivo enzyme’s catalyzed reactions has proven its success in solving toxicity and bioavailability related issues. On the other hand, prodrugs based on chemical interconversion in which the prodrug releases the corresponding active parent drug via inter or intramolecular chemical process in the absence of an enzyme is considered as a better alternative approach since the prodrug cleavage is not dependent in the efficiency or quantity of the enzyme catalyzes the interconversion of the prodrug. Examples of successful prodrugs using the chemical approach via intramolecular processes such as cyclization reactions are illustrated as well. In addition, another part of this review is devoted to cover reported studies on enzyme models and their utilization for the design and synthesis of a variety of novel prodrugs. In this approach, computational calculations using DFT and MM methods were exploited and correlations between experimentally determined and computed values of the rate-limiting step in the studied intramolecular processes were utilized in the prodrugs design. Selected examples of the designed prodrugs include aza-nucleosides for the treatment of myelodysplastic syndromes, the anti-Parkinson’s agent dopamine, the anti-viral acyclovir, the anti-malarial atovaquone, and statins for lowering cholesterol levels in the blood, the antihypertensive atenolol, the antibacterial cefuroxime, the anti-bleeding tranexamic acid, the decongestant phenylephrine, and the pain killer paracetamol

Intramolecular Processes and Their Applications in Prodrugs Approaches- Experimental and Computational Studies

This review supplies the reader with a detailed overview on the utilization of intramolecular processes for a design and synthesis of prodrugs. It is well known that a respected number of drugs suffer from low bioavailability, toxicity, unpleasant taste and presystemic first-pass metabolism which result in drug inactivation. The classical prodrug approach in which the linkage attaching the parent drug to its non-toxic linker and cleaved by in vivo enzyme’s catalyzed reactions has proven its success in solving toxicity and bioavailability related issues. On the other hand, prodrugs based on chemical interconversion in which the prodrug releases the corresponding active parent drug via inter or intramolecular chemical process in the absence of an enzyme is considered as a better alternative approach since the prodrug cleavage is not dependent in the efficiency or quantity of the enzyme catalyzes the interconversion of the prodrug. Examples of successful prodrugs using the chemical approach via intramolecular processes such as cyclization reactions are illustrated as well. In addition, another part of this review is devoted to cover reported studies on enzyme models and their utilization for the design and synthesis of a variety of novel prodrugs. In this approach, computational calculations using DFT and MM methods were exploited and correlations between experimentally determined and computed values of the rate-limiting step in the studied intramolecular processes were utilized in the prodrugs design. Selected examples of the designed prodrugs include aza-nucleosides for the treatment of myelodysplastic syndromes, the anti-Parkinson’s agent dopamine, the anti-viral acyclovir, the anti-malarial atovaquone, and statins for lowering cholesterol levels in the blood, the antihypertensive atenolol, the antibacterial cefuroxime, the anti-bleeding tranexamic acid, the decongestant phenylephrine, and the pain killer paracetamol

Antibacterial Predrugs-from 1899 till 2015

The predrug (prodrug) term involves chemically modified inert compound which upon an administration releases the active parent drug to elicit its pharmacological response within the body. For many years, the predrug strategy has been extensively developed to solve many unwanted drug properties. This approach has several advantages over conventional drug administration and it has the potential to be quite effective method for the treatment of diseases in the future. In this mini-review we describe a number of antibacterial agents‘ predrugs, and the ways by which predrug strategy was exploited to overcome many pharmaceutical and pharmacokinetic problems that the parent active antibacterial drugs suffer from such as, low bioavailability by increasing or decreasing lipophilicity, site selectivity for higher absorption and less toxicity, short duration of action to increase patient compliance, rapid metabolism to increase oral bioavailability and masking bitter sensation which is crucial for geriatric and pediatric patient compliance

ANTIBACTERIAL PREDRUGS-FROM 1899 TILL 2015

The classical approach for delivery of drugs into the central nervous system (CNS) is associated with adverse effects and it has many limitations. Therefore, extensive efforts have been done in searching and developing novel methods for achieving such delivery. This minireview discusses the design and synthesis of selected targeting prodrugs for the treatment of conditions related to impairment in the CNS such as Parkinson‘s and Alzheimer‘s diseases. Such approaches include targeting prodrugs which are designed to interact with unique cellular conditions at the target site, especially the availability of certain enzymes and transporters at these sites. In addition, part of this mini-review is devoted to prodrugs design based on enzyme models that have been invoked to understand how enzymes catalyzebiotransformation. In this approach, the prodrugs design isdone using quantum molecular orbital and molecular mechanics methods. The equations obtained from correlations of experimental and calculated rate values for some intramolecular processes are used to predict parameters for other intramolecular processes that can be utilized as prodrugs linkers. In this approach, there is no need for enzymes to catalyze the conversion of the prodrug to its active parent drug and the conversion rate of the prodrug is dependent only on those factors playing dominant role in the rate-limiting step of the 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 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

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

Skin Pigmentation Types, Causes and Treatment—A Review

Human skin pigmentation and melanin synthesis are incredibly variable, and are impacted by genetics, UV exposure, and some drugs. Patients’ physical appearance, psychological health, and social functioning are all impacted by a sizable number of skin conditions that cause pigmentary abnormalities. Hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced, are the two major classifications of skin pigmentation. Albinism, melasma, vitiligo, Addison’s disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosinase, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, 4 marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases