6 research outputs found
Antibacterial Prodrugs to Overcome Bacterial Resistance
Bacterial resistance to present antibiotics is emerging at a high pace that makes the
development of new treatments a must. At the same time, the development of novel antibiotics
for resistant bacteria is a slow-paced process. Amid the massive need for new drug treatments to
combat resistance, time and e ort preserving approaches, like the prodrug approach, are most needed.
Prodrugs are pharmacologically inactive entities of active drugs that undergo biotransformation before
eliciting their pharmacological e ects. A prodrug strategy can be used to revive drugs discarded due
to a lack of appropriate pharmacokinetic and drug-like properties, or high host toxicity. A special
advantage of the use of the prodrug approach in the era of bacterial resistance is targeting resistant
bacteria by developing prodrugs that require bacterium-specific enzymes to release the active drug.
In this article, we review the up-to-date implementation of prodrugs to develop medications that are
active against drug-resistant bacteria.Acknowledgments: The authors would like to thank Al-Quds University-Scientific Research O ce for covering
the publication fees for this review article
Enzyme Models—From Catalysis to Prodrugs
Enzymes are highly specific biological catalysts that accelerate the rate of chemical reac-tions within the cell. Our knowledge of how enzymes work remains incomplete. Computationalmethodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play animportant role in elucidating the detailed mechanisms of enzymatic reactions where experimentalresearch measurements are not possible. Theories invoked by a variety of scientists indicate thatenzymes work as structural scaffolds that serve to bring together and orient the reactants so that thereaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzymecatalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokineticsof drugs; classical prodrug approaches focus on alternating the physicochemical properties, whilechemical modern approaches are based on the knowledge gained from the chemistry of enzymemodels and correlations between experimental and calculated rate values of intramolecular processes(enzyme models). A large number of prodrugs have been designed and developed to improve theeffectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), an-tiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamicacid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol),antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin.This article describes the works done on enzyme models and the computational methods used tounderstand enzyme catalysis and to help in the development of efficient prodrugs
Comprehensive Review on Alzheimer’s Disease: Causes and Treatment
Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in the brain
and it is the main cause of dementia, which is characterized by a decline in thinking and
independence in personal daily activities. AD is considered a multifactorial disease: two main
hypotheses were proposed as a cause for AD, cholinergic and amyloid hypotheses. Additionally,
several risk factors such as increasing age, genetic factors, head injuries, vascular diseases,
infections, and environmental factors play a role in the disease. Currently, there are only two classes
of approved drugs to treat AD, including inhibitors to cholinesterase enzyme and antagonists to Nmethyl
D-aspartate (NMDA), which are effective only in treating the symptoms of AD, but do not
cure or prevent the disease. Nowadays, the research is focusing on understanding AD pathology by
targeting several mechanisms, such as abnormal tau protein metabolism, β-amyloid, inflammatory
response, and cholinergic and free radical damage, aiming to develop successful treatments that are
capable of stopping or modifying the course of AD. This review discusses currently available drugs
and future theories for the development of new therapies for AD, such as disease-modifying
therapeutics (DMT), chaperones, and natural compounds
Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses
For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational
and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis
plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent
of cannabis is ∆9-tetrahydrocannabinol (∆9-THC). The pharmacological effects of cannabinoids are a
result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in
many parts of the human body. Cannabis is used as a therapeutic agent for treating pain and emesis.
Some cannabinoids are clinically applied for treating chronic pain, particularly cancer and multiple
sclerosis-associated pain, for appetite stimulation and anti-emesis in HIV/AIDS and cancer patients,
and for spasticity treatment in multiple sclerosis and epilepsy patients. Medical cannabis varies from
recreational cannabis in the chemical content of THC and cannabidiol (CBD), modes of administration,
and safety. Despite the therapeutic effects of cannabis, exposure to high concentrations of THC,
the main compound that is responsible for most of the intoxicating effects experienced by users,
could lead to psychological events and adverse effects that affect almost all body systems, such as
neurological (dizziness, drowsiness, seizures, coma, and others), ophthalmological (mydriasis and
conjunctival hyperemia), cardiovascular (tachycardia and arterial hypertension), and gastrointestinal
(nausea, vomiting, and thirst), mainly associated with recreational use. Cannabis toxicity in children is
more concerning and can cause serious adverse effects such as acute neurological symptoms (stupor),
lethargy, seizures, and even coma. More countries are legalizing the commercial production and
sale of cannabis for medicinal use, and some for recreational use as well. Liberalization of cannabis
laws has led to increased incidence of toxicity, hyperemesis syndrome, lung disease cardiovascular
disease, reduced fertility, tolerance, and dependence with chronic prolonged use. This review focuses
on the potential therapeutic effects of cannabis and cannabinoids, as well as the acute and chronic
toxic effects of cannabis use on various body systems
Comprehensive Review on Alzheimer’s Disease: Causes and Treatment
Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in the brain and it is the main cause of dementia, which is characterized by a decline in thinking and independence in personal daily activities. AD is considered a multifactorial disease: two main hypotheses were proposed as a cause for AD, cholinergic and amyloid hypotheses. Additionally, several risk factors such as increasing age, genetic factors, head injuries, vascular diseases, infections, and environmental factors play a role in the disease. Currently, there are only two classes of approved drugs to treat AD, including inhibitors to cholinesterase enzyme and antagonists to N-methyl d-aspartate (NMDA), which are effective only in treating the symptoms of AD, but do not cure or prevent the disease. Nowadays, the research is focusing on understanding AD pathology by targeting several mechanisms, such as abnormal tau protein metabolism, β-amyloid, inflammatory response, and cholinergic and free radical damage, aiming to develop successful treatments that are capable of stopping or modifying the course of AD. This review discusses currently available drugs and future theories for the development of new therapies for AD, such as disease-modifying therapeutics (DMT), chaperones, and natural compounds
Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It
Antimicrobial resistance represents an enormous global health crisis and one of the most serious threats humans face today. Some bacterial strains have acquired resistance to nearly all antibiotics. Therefore, new antibacterial agents are crucially needed to overcome resistant bacteria. In 2017, the World Health Organization (WHO) has published a list of antibiotic-resistant priority pathogens, pathogens which present a great threat to humans and to which new antibiotics are urgently needed the list is categorized according to the urgency of need for new antibiotics as critical, high, and medium priority, in order to guide and promote research and development of new antibiotics. The majority of the WHO list is Gram-negative bacterial pathogens. Due to their distinctive structure, Gram-negative bacteria are more resistant than Gram-positive bacteria, and cause significant morbidity and mortality worldwide. Several strategies have been reported to fight and control resistant Gram-negative bacteria, like the development of antimicrobial auxiliary agents, structural modification of existing antibiotics, and research into and the study of chemical structures with new mechanisms of action and novel targets that resistant bacteria are sensitive to. Research efforts have been made to meet the urgent need for new treatments; some have succeeded to yield activity against resistant Gram-negative bacteria by deactivating the mechanism of resistance, like the action of the β-lactamase Inhibitor antibiotic adjuvants. Another promising trend was by referring to nature to develop naturally derived agents with antibacterial activity on novel targets, agents such as bacteriophages, DCAP(2-((3-(3,6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl)amino)-2(hydroxymethyl)propane1,3-diol, Odilorhabdins (ODLs), peptidic benzimidazoles, quorum sensing (QS) inhibitors, and metal-based antibacterial agents