New Generation Of Drugs Research Articles

The inhibitory effect of indisulam-coumarin combined therapy on glioblastoma multiforme

Cancer is a disease that occurs due to irregular growth and proliferation of body cells and can be caused by many factors. One of these factors is carbonic anhydrase 9 (CAIX). While its expression is high in malignant cells, it is a molecule whose presence is difficult to detect in healthy tissues. Glioblastoma multiforme (GBM) is one of the fast-spreading brain cancers, and unlike healthy tissues, overexpressed CAIX in its cell receptors. Indisulam, one of the new-generation drug candidates for the treatment of solid tumours, is a type of CAIX inhibitor that affects cell division progression in human tumour cells. Similarly, it is known that coumarin, as one of the new-generation drugs in cancer treatment, is used together with chemotherapy. In this study, combined treatment of indisulam and coumarin was investigated on glioblastoma multiforme cells to evaluate their cytotoxicity, cell migration and antiproliferative effects. The effects of combined treatment on cell migration and proliferation were investigated with the IC50 values determined after the cytotoxicity test. As a result of the wound healing assay, it was determined that the control cells were closed by 69.6%, while the combined treatment closed the wound by 32% and seriously prevented cell migration. The percentage of proliferative cell nuclear antigen (PCNA) positive cells decreased significantly after combined treatment, cell proliferation was 93% in the control group and 77% in the combined treatment group.

Research on the current status and future prospects in the development of antidepressant drugs

Depression is a significant global health burden, affecting millions of people worldwide. The development of antidepressant drugs has been crucial in providing relief for individuals suffering from depression. This paper reviews the current status of antidepressant drug development, focusing on various classes of antidepressants, their mechanisms of action, and the challenges faced during their development. Additionally, the paper discusses potential future directions in antidepressant drug research, including novel targets, personalized medicine approaches, and emerging technologies. Understanding the current state and future prospects of antidepressant drug development is vital to advancing treatment options for individuals with depression and improving their quality of life. The paper finds the main drawbacks of traditional antidepressant drugs and focuses on the outlook of the new generation of drugs, the research process, and potential benefits.

HER3: Toward the Prognostic Significance, Therapeutic Potential, Current Challenges, and Future Therapeutics in Different Types of Cancer.

Human epidermal growth factor receptor 3 (HER3) is the only family member of the EGRF/HER family of receptor tyrosine kinases that lacks an active kinase domain (KD), which makes it an obligate binding partner with other receptors for its oncogenic role. When HER3 is activated in a ligand-dependent (NRG1/HRG) or independent manner, it can bind to other receptors (the most potent binding partner is HER2) to regulate many biological functions (growth, survival, nutrient sensing, metabolic regulation, etc.) through the PI3K-AKT-mTOR pathway. HER3 has been found to promote tumorigenesis, tumor growth, and drug resistance in different cancer types, especially breast and non-small cell lung cancer. Given its ubiquitous expression across different solid tumors and role in oncogenesis and drug resistance, there has been a long effort to target HER3. As HER3 cannot be targeted through its KD with small-molecule kinase inhibitors via the conventional method, pharmaceutical companies have used various other approaches, including blocking either the ligand-binding domain or extracellular domain for dimerization with other receptors. The development of treatment options with anti-HER3 monoclonal antibodies, bispecific antibodies, and different combination therapies showed limited clinical efficiency for various reasons. Recent reports showed that the extracellular domain of HER3 is not required for its binding with other receptors, which raises doubt about the efforts and applicability of the development of the HER3-antibodies for treatment. Whereas HER3-directed antibody-drug conjugates showed potentiality for treatment, these drugs are still under clinical trial. The currently understood model for dimerization-induced signaling remains incomplete due to the absence of the crystal structure of HER3 signaling complexes, and many lines of evidence suggest that HER family signaling involves more than the interaction of two members. This review article will significantly expand our knowledge of HER3 signaling and shed light on developing a new generation of drugs that have fewer side effects than the current treatment regimen for these patients.

Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis.

Antithrombotic therapy is a delicate balance between the benefits of preventing a thrombotic event and the risks of inducing a major bleed. Traditional approaches have included antiplatelet and anticoagulant medications, require careful dosing and monitoring, and all carry some risk of bleeding. In recent years, several new targets have been identified, both in the platelet and coagulation systems, which may mitigate this bleeding risk. In this review, we briefly describe the current state of antithrombotic therapy, and then present a detailed discussion of the new generation of drugs that are being developed to target more safely existing or newly identified pathways, alongside the strategies to reverse direct oral anticoagulants, showcasing the breadth of approaches. Combined, these exciting advances in antithrombotic therapy bring us closer than we have ever been to the "holy grail" of the field, a treatment that separates the hemostatic and thrombotic systems, preventing clots without any concurrent bleeding risk.

Phosphodiesterase 2 and Its Isoform a as Therapeutic Targets in the Central Nervous System Disorders.

Cyclic adenosine monophosphates (cAMP) and cyclic guanosine monophosphate (cGMP) are two essential second messengers, which are hydrolyzed by phosphodiesterase's (PDEs), such as PDE-2. Pharmacological inhibition of PDE-2 (PDE2A) in the central nervous system improves cAMP and cGMP signaling, which controls downstream proteins related to neuropsychiatric, neurodegenerative, and neurodevelopmental disorders. Considering that there are no specific treatments for these disorders, PDE-2 inhibitors' development has gained more attention in the recent decade. There is high demand for developing new-generation drugs targeting PDE2 for treating diseases in the central nervous and peripheral systems. This review summarizes the relationship between PDE-2 with neuropsychiatric, neurodegenerative, and neurodevelopmental disorders as well as its possible treatment, mainly involving inhibitors of PDE2.

Anti-amyloid antibody treatments for Alzheimer's disease.

Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid-β. This is a joint statement of the European Association of Neurology and the European Psychiatric Association. After numerous unsuccessful endeavors to create a disease-modifying therapy for Alzheimer's disease, substantial and consistent evidence supporting the clinical effectiveness of monoclonal antibodies aimed at amyloid-β is finally emerging. The latest trials not only achieved their primary objective of slowing the progression of the disease over several months but also demonstrated positive secondary clinical outcomes and a decrease in amyloid-β levels as observed through positron emission tomography scans. Taken as a whole, these findings mark a significant breakthrough by substantiating that reducing amyloid-β yields tangible clinical benefits, beyond mere changes in biomarkers. Concurrently, the regular utilization of the new generation of drugs will determine whether statistical efficacy translates into clinically meaningful improvements. This may well signify the dawning of a new era in the development of drugs for Alzheimer's disease.

Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-β Therapy.

Alzheimer disease (AD) is the most common form of dementia worldwide. Treatment of AD has mainly been focused on symptomatic treatment until recently with the advent and approval of monoclonal antibody (MAB) immunotherapy. U.S. Food and Drug Administration-approved drugs such as aducanumab, as well as upcoming newer-generation drugs, have provided an exciting new therapy focused on reducing the amyloid plaque burden in AD. Although this new frontier has shown benefits for patients, it is not without complications, which are mainly neurologic. Increased use of MABs led to the discovery of amyloid-related imaging abnormalities (ARIA). ARIA has been further classified into two categories, ARIA-E and ARIA-H, representing edema and/or effusion and hemorrhage, respectively. ARIA is thought to be caused by increased vascular permeability following an inflammatory response, leading to the extravasation of blood products and proteinaceous fluid. Patients with ARIA may present with headaches, but they are usually asymptomatic and ARIA is only diagnosable at MRI; it is essential for the radiologist to recognize and monitor ARIA. Increased incidence and investigation into this concern have led to the creation of grading scales and monitoring guidelines to diagnose and guide treatment using MABs. Cerebral amyloid angiopathy has an identical pathogenesis to that of ARIA and is its closest differential diagnosis, with imaging findings being the same for both entities and only a history of MAB administration allowing differentiation. The authors discuss the use of MABs for treating AD, expand on ARIA and its consequences, and describe how to identify and grade ARIA to guide treatment properly. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center See the invited commentary by Yu in this issue.

The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies.

Almost 17% of Western patients affected by non-small cell lung cancer (NSCLC) have an activating epidermal growth factor receptor (EGFR) gene mutation. Del19 and L858R are the most-common ones; they are positive predictive factors for EGFR tyrosine kinase inhibitors (TKIs). Currently, osimertinib, a third-generation TKI, is the standard first-line therapy for advanced NSCLC patients with common EGFR mutations. This drug is also administered as a second-line treatment for those patients with the T790M EGFR mutation and previously treated with first- (erlotinib, gefitinib) or second- (afatinib) generation TKIs. However, despite the high clinical efficacy, the prognosis remains severe due to intrinsic or acquired resistance to EGRF-TKIs. Various mechanisms of resistance have been reported including the activation of other signalling pathways, the development of secondary mutations, the alteration of the downstream pathways, and phenotypic transformation. However, further data are needed to achieve the goal of overcoming resistance to EGFR-TKIs, hence the necessity of discovering novel genetic targets and developing new-generation drugs. This review aimed to deepen the knowledge of intrinsic and acquired molecular mechanisms of resistance to EGFR-TKIs and the development of new therapeutic strategies to overcome TKIs' resistance.

Supplementing traditional drug formulation with the “needed” gases opens the way for the development of a new generation of drugs

The mechanism of action of drugs is traditionally considered the specific action of the main active ingredients. Therefore, to study the mechanism of action of drugs, specialists use selected chemical compounds in chemically pure form. However, at the beginning of the 21st century, studies have reported that the action of drugs in dosage forms (tablets, solutions, etc.) is different from the action of chemically pure ingredients. The fact is that tablets, solutions, and other dosage forms contain not only the main ingredients but also auxiliary, shape-forming ingredients, and gases that supplement the specific action of the main ingredients with their nonspecific action. The gases penetrate the dosage forms from the air; however, selected gases can be introduced into the drugs under excessive pressure. Evidence presents that purposefully altering the gas content of drug tablets and solutions can regulate their mass, volume, specific gravity, porosity, physicochemical activity, and local pharmacokinetics and pharmacodynamics, especially when drugs are administered locally. Examples are shown on how the use of this regularity has allowed the development of a new generation of drugs in Russia, namely, drugs with a specific gas composition. Studies have reported that changing the gas composition of old (registered) drugs may turn them into new drugs. Some drugs invented in Russia included gases in their formulation, which play the role of auxiliary, shape-forming, and even main ingredients. Thus, the gas composition of drugs was proposed as an additional indicator of their quality and an important factor in their physicochemical activity. An expanded list of new generation drugs was hoped for in the near future.

A combination preparation based on antibiotic, cluster silver and bacteriophage for treatment of infectious diseases caused by <i>Staphylococcus aureus</i> and <i>S. aureus</i> MRSA

The problems of bacterial infections in medicine and veterinary medicine require careful study and rapid solution. Due to continuous and, in some cases, irrational use of antibiotics, the efficiency of their effect on host has been noticeably decreasing; moreover, resistance to antibacterial drugs is steadily growing, antibiotic-resistant strains emerge, which are not amenable to conventional medical treatment. The unprecedented rise of pathogenic bacteria resistance to antibiotics requires generation of new drugs to combat them. One of the ways to increase the effectiveness of antibiotic therapy is to use combination drugs. Combination dosage forms provide an increased therapeutic effect and should not be toxic to the body. To overcome the microbial resistance reducing host burden of antibiotics, we proposed a combination preparation based on antibiotic, cluster silver and specific bacteriophage for treatment of infectious diseases caused by S. aureus, including MRSA strains. Each component has already proven in the treatment of pathogen-caused infectious diseases. But while using this combination agent, it became possible to reduce the amount of antibiotic and get rid of antibiotic-resistant and phage-resistant forms of bacteria. The study showed the effectiveness of the combination preparation on S. aureus MRSA bacteria, while reducing the amount of antibiotics in proposed composition by 24 times compared to use of antibiotic alone. The efficacy of the preparation containing was as follows: 10 mg/ml gentamicin, 7 mg/ml cluster silver and 106 BOV/ml bacteriophage, on S. aureus MRSA bacteria in suspension is comparable to the effectiveness of gentamicin with a concentration of 40 mg/ml. For S. aureus 209 and S. aureus ssp. bacteria with reduced resistance to antibiotics, the use of two-component compositions (antibiotic + cluster silver; antibiotic + bacteriophage) also allowed to reduce the antibiotic concentration by 23 times. It should be noted that with a constant amount of antibiotic, increasing the amount of cluster silver by 45 times, there is a rise in bactericidal properties of the resulting preparations. Repeated introduction of drug dose allows to achieve a marked decrease in level of pathogenic microorganisms in the suspension studied. This drug has no limitations depending on the state and degree of microbial resistance.

Development of New Generation Drugs by Enriching Them with Gases

Until today, the mechanism of action of drugs is traditionally considered without taking into account the physical-chemical properties of dosage forms. However, at the beginning of the 21st century, there were reports that all drugs contain unaccounted gases that enter drugs from the air and affect the quality of drugs. It is shown that the composition and amount of gases in the dosage forms of all drugs changes their mechanical, physical, chemical and physical-chemical properties and the mechanism of action of drugs, especially when applied topically It is reported that changing the content of gases in drug solutions and tablets allows to regulate their mass, volume, specific gravity, porosity, physico-chemical activity and local action on the routes of drug administration. The identification of this pattern allowed to start the production of completely new drugs with a certain gas composition and with a new local pharmacokinetics and a new local pharmacodynamics. The formulations of new drugs in which gas is an auxiliary, formative or main ingredient are given. It is proposed to control the gas composition of medicines as an indicator of their quality and an important factor of their physical-chemical activity. It is proved that the gas in the drug can be not only neutral, but also auxiliary, oppositional, and sometimes the main ingredient. Thus, the control and accounting of the gas contained in drugs will allow the creation of a new generation of drugs in the near future.

Targeting Transcription Factors ATF5, CEBPB and CEBPD with Cell-Penetrating Peptides to Treat Brain and Other Cancers.

Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we recount the evidence identifying the basic leucine zipper transcription factors ATF5, CEBPB, and CEBPD as targets for brain and other malignancies. We describe strategies that exploit the structures of the three factors to create inhibitory dominant-negative (DN) mutant forms that selectively suppress growth and survival of cancer cells. We then discuss and compare four peptides (CP-DN-ATF5, Dpep, Bpep and ST101) in which DN sequences are joined with cell-penetrating domains to create drugs that pass through tissue barriers and into cells. The peptide drugs show both efficacy and safety in suppressing growth and in the survival of brain and other cancers in vivo, and ST101 is currently in clinical trials for solid tumors, including GBM. We further consider known mechanisms by which the peptides act and how these have been exploited in rationally designed combination therapies. We additionally discuss lacunae in our knowledge about the peptides that merit further research. Finally, we suggest both short- and long-term directions for creating new generations of drugs targeting ATF5, CEBPB, CEBPD, and other transcription factors for treating brain and other malignancies.

Resveratrol and Cervical Cancer: A New Therapeutic Option.

Globally, cervical cancer is the second most common cancer and the third main cause of death related to cancer in women. The cervical cancer mortality rate is higher in underdeveloped and developing vs. developed countries. Chronic infection with human papilloma virus (HPV) can trigger cervical cancer by an interplay of a variety of pathways and molecules (i.e., inflammatory mediators, oxidative stress and apoptosis), leading to carcinogenesis and cancer progression. Cervical carcinoma is treatable in the early stages, while it progresses to metastasis at advanced stages; however, generally, it is poorly manageable with current treatment options. For future advances in the treatment of metastatic or recurrent cervical cancer carcinoma, the identification of new therapeutic platforms is necessary. A new generation of drugs, herbs and spices may provide novel opportunities for cancer therapy. Among the herb-based components, resveratrol has several beneficial effects given its anticancer activities (e.g., anti-angiogenesis, anti-proliferation, anti-metastatic and pro-apoptotic). Hence, this therapeutic agent may prove to have promising potential if clinically corroborated to possess anticancer efficacy. Here, we summarize the chemopreventive and treatment actions of resveratrol for cervical cancer as well as its mechanism of action.

Emergence of microbial resistance against nanoparticles: Mechanisms and strategies.

Antimicrobial nanoparticles have gained the status of a new generation of drugs that can kill bacterial pathogens by multiple means; however, nanoparticle resistance acquired by some bacterial pathogens has evoked a cause of concern. Several reports suggested that bacteria can develop nanoparticles, specifically metal nanoparticle resistance, by mechanisms: nanoparticle transformation-induced oxidative stress, membrane alterations, reversible adaptive resistance, irreversible modifications to cell division, and a change in bacterial motility and resistance. Surface properties, concentration and aggregation of nanoparticles, biofilm forming and metal exclusion capacity, and R plasmid and flagellin synthesis by bacteria are crucial factors in the development of nanoparticle resistance in bacteria. Studies reported the resistance reversal by modifying the surface corona of nanoparticles or inhibiting flagellin production by bacterial pathogens. Furthermore, strict regulation regarding the use and disposal of nano-waste across the globe, the firm knowledge of microbe-nanoparticle interaction, and the regulated disposal of nanoparticles in soil and water is required to prevent microbes from developing nanoparticle resistance.

Anti-amyloid antibody therapies in Alzheimer's disease.

After years of failed attempts to develop a disease-modifying therapy for Alzheimer's disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-β protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-β lowering on PET also underpin the positive results of the trial. In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer's disease failed. We compare the safety profiles of the different antibodies and highlight cautionary measures for their routine clinical use. Last, we discuss the role of blood-based biomarkers in transforming the clinical care pathway to facilitate the uptake of antibody treatments, proposing an integrated case-finding and treatment model crossing the different healthcare sectors. Taken together, a real breakthrough may have been achieved by proving that amyloid-β reduction results in clinical benefits, rather than just biomarker changes. At the same time, routine use of the new generation of drugs will show if statistical efficacy translates into clinically meaningful change. This may just be the beginning of a new era of Alzheimer's disease drug development.

On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease

Protein aggregation, mitochondrial dysfunction, iron dyshomeostasis, increased oxidative damage and inflammation are pathognomonic features of Parkinson's disease (PD) and other neurodegenerative disorders characterized by abnormal iron accumulation. Moreover, the existence of positive feed-back loops between these pathological components, which accelerate, and sometimes make irreversible, the neurodegenerative process, is apparent. At present, the available treatments for PD aim to relieve the symptoms, thus improving quality of life, but no treatments to stop the progression of the disease are available. Recently, the use of multifunctional compounds with the capacity to attack several of the key components of neurodegenerative processes has been proposed as a strategy to slow down the progression of neurodegenerative processes. For the treatment of PD specifically, the necessary properties of new-generation drugs should include mitochondrial destination, the center of iron-reactive oxygen species interaction, iron chelation capacity to decrease iron-mediated oxidative damage, the capacity to quench free radicals to decrease the risk of ferroptotic neuronal death, the capacity to disrupt α-synuclein aggregates and the capacity to decrease inflammatory conditions. Desirable additional characteristics are dopaminergic neurons to lessen unwanted secondary effects during long-term treatment, and the inhibition of the MAO-B and COMPT activities to increase intraneuronal dopamine content. On the basis of the published evidence, in this work, we review the molecular basis underlying the pathological events associated with PD and the clinical trials that have used single-target drugs to stop the progress of the disease. We also review the current information on multifunctional compounds that may be used for the treatment of PD and discuss the chemical characteristics that underlie their functionality. As a projection, some of these compounds or modifications could be used to treat diseases that share common pathology features with PD, such as Friedreich's ataxia, Multiple sclerosis, Huntington disease and Alzheimer's disease.

Role of Notch2 pathway in mature B cell malignancies.

In recent decades, the Notch pathway has been characterized as a key regulatory signaling of cell-fate decisions evolutionarily conserved in many organisms and different tissues during lifespan. At the same time, many studies suggest a link between alterations of this signaling and tumor genesis or progression. In lymphopoiesis, the Notch pathway plays a fundamental role in the correct differentiation of T and B cells, but its deregulated activity leads to leukemic onset and evolution. Notch and its ligands Delta/Jagged exhibit a pivotal role in the crosstalk between leukemic cells and their environment. This review is focused in particular on Notch2 receptor activity. Members of Notch2 pathway have been reported to be mutated in Chronic Lymphocytic Leukemia (CLL), Splenic Marginal Zone Lymphoma (SMZL) and Nodal Marginal Zone Lymphoma (NMZL). CLL is a B cell malignancy in which leukemic clones establish supportive crosstalk with non-malignant cells of the tumor microenvironment to grow, survive, and resist even the new generation of drugs. SMZL and NMZL are indolent B cell neoplasms distinguished by a distinct pattern of dissemination. In SMZL leukemic cells affect mainly the spleen, bone marrow, and peripheral blood, while NMZL has a leading nodal distribution. Since Notch2 is involved in the commitment of leukemic cells to the marginal zone as a major regulator of B cell physiological differentiation, it is predominantly affected by the molecular lesions found in both SMZL and NMZL. In light of these findings, a better understanding of the Notch receptor family pathogenic role, in particular Notch2, is desirable because it is still incomplete, not only in the physiological development of B lymphocytes but also in leukemia progression and resistance. Several therapeutic strategies capable of interfering with Notch signaling, such as monoclonal antibodies, enzyme or complex inhibitors, are being analyzed. To avoid the unwanted multiple "on target" toxicity encountered during the systemic inhibition of Notch signaling, the study of an appropriate pharmaceutical formulation is a pressing need. This is why, to date, there are still no Notch-targeted therapies approved. An accurate analysis of the Notch pathway could be useful to drive the discovery of new therapeutic targets and the development of more effective therapies.

Manganese enhances macrophage defense against Mycobacterium tuberculosis via the STING-TNF signaling pathway.

The host cell antiviral response pathway depends heavily on manganese (Mn), but its role in defense against Mycobacterium tuberculosis (M. tuberculosis) infection is rarely reported. In this study, we found that, in H37Ra-infected macrophages, Mn2+ increases the phosphorylation of stimulator of interferon genes (STING) and P65, as well as triggers the phosphorylation cascade of tumor necrosis factor (TNF) signaling pathway proteins, signal-regulated kinase (ERK), P38, and c-Jun N-terminal kinase (JNK). The activation of the TNF signaling pathway stimulated the expression of downstream inflammatory factors TNF-α, C-X-C Motif Chemokine Ligand 10(CXCL10), CC Motif Chemokine Ligand 20(CCL20), Colony Stimulating Factor 1(CSF1), Colony Stimulating Factor 2(CSF2), and Jagged Canonical Notch Ligand 1(JAG1), thereby triggering a strong inflammatory response in the cells. The excessive accumulation of TNF-α in macrophages induces necroptosis and inhibits the survival of M. tuberculosis in macrophages. When we treated macrophages with the STING inhibitor H-151, the phosphorylation of P38 was reduced, and the secretion of downstream inflammatory factors TNF-α and CXCL10, CCL20, CSF1, and CSF2 were also inhibited. Overall, this study reveals that Mn2+ plays a crucial role in host cell defense against M. tuberculosis infection, contributes to a deeper understanding of pathogen-host interactions, and offers theoretical support for the use of Mn2+ as a drug cofactor for the treatment of tuberculosis and the development of a new generation of drugs and vaccine adjuvants.

A Perspective on Newly Emerging Proteolysis-Targeting Strategies in Antimicrobial Drug Discovery.

Targeted protein degradation is a new aspect in the field of drug discovery. Traditionally, developing an antibiotic includes tedious and expensive processes, such as drug screening, lead optimization, and formulation. Proteolysis-targeting chimeras (PROTACs) are new-generation drugs that use the proteolytic mechanism to selectively degrade and eliminate proteins involved in human diseases. The application of PROTACs is explored immensely in the field of cancer, and various PROTACs are in clinical trials. Thus, researchers have a profound interest in pursuing PROTAC technology as a new weapon to fight pathogenic viruses and bacteria. This review highlights the importance of antimicrobial PROTACs and other similar "PROTAC-like" techniques to degrade pathogenic target proteins (i.e., viral/bacterial proteins). These techniques can perform specific protein degradation of the pathogenic protein to avoid resistance caused by mutations or abnormal expression of the pathogenic protein. PROTAC-based antimicrobial therapeutics have the advantage of high specificity and the ability to degrade "undruggable" proteins, such as nonenzymatic and structural proteins.

Citrus pectin based complexes for the tetracycline delivery

This research studied the formation of sodium polygalacturonate complexes with the antimicrobial drug "Tetracycline". The formation was confirmed by IR, UV and NMR spectroscopy. It was shown that the complexes were formed by electrostatic attraction and hydrogen bonding. The complexes demonstrated a high degree of drug binding to the polysaccharide matrix with the maximum content of tetracycline (6.68 wt %). The study of the antimicrobial activity of obtained compounds against S. aureus, B. cereus, E. coli showed no decrease in the antimicrobial effect compared to source tetracycline. Thus, the future research towards the new design compounds based on studied complexes could make contribution to a new generation of drugs based on pectin biopolymers.