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1.
Article in English | MEDLINE | ID: mdl-38778618

ABSTRACT

BACKGROUND: Eliminating and managing L. monocytogenes, L. welshimeri, and L. ivanovii biofilms is a significant problem for food safety, as listeriosis is among the worst foodborne illnesses. METHOD: The Listex P100 bacteriophage's bactericidal and inhibitory properties have been investigated in relation to varying strains of vegetative cells and biofilms of L. monocytogenes, L. welshimeri, and L. ivanovii. RESULTS: The phage concentrations of 109 and 1010 PFU/ml showed strong antibacterial activity against L. monocytogenes, L. welshimeri, and L. ivanovii at both 10°C and 30°C (P<0.05). In 96- well microplate experiments, bacteriophage treatment inhibited biofilm development and reduced biofilm by up to 57.6% (P ≤ 0.05). When compared to controls, Listex P100 bacteriophage significantly reduced the populations of L. monocytogenes, L. welshimeri, and L. ivanovii biofilms on the surfaces of galvanised, stainless steel, and plastic surfaces where holes were produced and the structure of Listeria spp. was disturbed. CONCLUSION: This study clearly demonstrated that L. monocytogenes, L. welshimeri, and L. ivanovii biofilms on galvanised, stainless steel, and plastic surfaces might be removed by using Listex P100 bacteriophage.

2.
Curr Protein Pept Sci ; 24(7): 551-566, 2023.
Article in English | MEDLINE | ID: mdl-37496250

ABSTRACT

As more antibiotics become ineffective due to drug-resistant bacteria, alternative therapies for infections must be prioritized. While pathogenic bacteria are a major threat, they also supply a massive reservoir of potential drugs for treating a wide range of illnesses. The concerning emergence of antimicrobial resistance and the rapidly dwindling therapeutic pipeline need the quick discovery and development of new antibiotics. Despite their great promise for natural product medicine development, pathogenic microorganisms have remained mostly unexplored and understudied. We review the antibacterial activity of specialized metabolites derived from pathogenic bacteria, emphasizing those presently in pre-clinical studies or with promise for medication development. Several atypical biosynthetic pathways are outlined, together with the crucial functions. We also discuss the mechanism of action and antibacterial activities of the antibiotics under consideration. Pathogenic bacteria as a rich source of antibiotics, along with recent advances in genomics and natural product research methods, may usher in a new golden age of antibiotic discovery.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Peptides , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria , Genomics , Drug Development
3.
Curr Drug Targets ; 24(7): 613-625, 2023.
Article in English | MEDLINE | ID: mdl-37211854

ABSTRACT

INTRODUCTION: Salmonellosis, which is typically distinguished by an immediate onset of fever, abdominal pain, diarrhea, nausea, and vomiting, is a bacterial infection caused by Salmonella. The rising incidence of antibiotic resistance in Salmonella Typhimurium is a major worldwide problem, and a better knowledge of the distribution of antibiotic resistance patterns in Salmonella Typhimurium is critical for selecting the best antibiotic for infection treatment. In this work, the efficiency of bacteriophage therapy of vegetative cells and biofilms of S. Typhimurium was investigated. METHODS: Based on their host ranges, five Bacteriophages were chosen for therapy against 22 Salmonella isolates collected from various sources. PSCs1, PSDs1, PSCs2, PSSr1, and PSMc1 phages were found to exhibit potent anti-S. Typhimurium properties. In a 96-well microplate, the efficacy of bacteriophage therapy (105-1011 PFU/mL) against S. Typhimurium biofilm formers was first tested. A bacteriophage treatment (109 PFU/mL) was subsequently applied in the laboratory for 24 hours to minimize Salmonella adhering to the surfaces of gallstones and teeth. In 96-well microplate experiments, bacteriophage treatment inhibited biofilm development and reduced biofilm by up to 63.6% (P ≤ 0.05). RESULT: When compared to controls, bacteriophages (PSCs1, PSDs1, PSCs2, PSSr1, PSMc1) demonstrated a rapid drop in the populations of S. Typhimurium biofilms generated on the surfaces of gallstones and teeth where the structure of the Salmonella bacteria in the biofilm was broken and holes were created. CONCLUSION: Clearly, this study indicated that phages might be employed to eliminate S. Typhimurium biofilms on gallstone and tooth surfaces.


Subject(s)
Bacteriophages , Gallstones , Humans , Gallstones/microbiology , Biofilms , Salmonella typhimurium , Anti-Bacterial Agents/pharmacology
4.
Comb Chem High Throughput Screen ; 26(11): 1945-1959, 2023.
Article in English | MEDLINE | ID: mdl-36366840

ABSTRACT

SARS-CoV-2 is a disease that endangers both human life and the economy. There was an 11- month period of relative evolutionary standstill following the appearance of SARS-CoV-2 in late 2019. However, the emergence of clusters of mutations known as' variants of concern 'with variable viral properties such as transmissibility and antigenicity defined the evolution of SARS-CoV-2. Several efforts have been made in recent months to understand the atomic level properties of SARS-CoV-2. A review of the literature on SARS-CoV-2 mutations is offered in this paper. The critical activities performed by different domains of the SARS-CoV-2 genome throughout the virus's entry into the host and overall viral life cycle are discussed in detail. These structural traits may potentially pave the way for the development of a vaccine and medication to combat the SARS-CoV-2 sickness.


Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2/genetics , Vaccine Development , Mutation , Phenotype
5.
Curr Protein Pept Sci ; 23(5): 356-368, 2022.
Article in English | MEDLINE | ID: mdl-35786184

ABSTRACT

BACKGROUND: Infection caused by multidrug-resistant K. pneumoniae is regarded as a severe public health concern worldwide, with most countries reporting an increase in fatality rates over time. Efflux pumps are significant determinants of acquired and/or intrinsic resistance in K. pneumoniae. OBJECTIVES: Our aim is to explore efflux-mediated resistance mechanisms in K. pneumoniae by using quantitative real-time PCR in order to evaluate the expression of efflux pump genes (acrA, acrB, oqxA, and oqxB) and pump regulators (marA, soxS, and rarA). METHODS: Efflux pump inhibitor CCCP reduced MIC values of ciprofloxacin by 2 to 64-fold in 43/46 (93%) of MDR-K. pneumoniae isolates. RESULTS: Compared to the control strain (untreated one), our results demonstrated that acrA, acrB, oqxA, oqxB, marA, soxS, and rarA were overexpressed in 29 (63%), 24 (52%), 29 (63%), 24 (52%), 17 (37%), 16 (35%), and 16 (35%) of K. pneumoniae isolates, respectively. Additionally, a positive correlation was established between the expressions of acrAB and marA (r = 0.50, r = 0.45, respectively) and oqxAB and rarA (r = 0.462912, r = 0.519354, respectively). CONCLUSION: Ciprofloxacin resistance was caused by overexpression of the efflux pump genes acrAB and oqxAB, as well as the transcriptional regulators marA, soxS, and rarA in clinical isolates of K. pneumonia.


Subject(s)
Drug Resistance, Bacterial , Klebsiella pneumoniae , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Ciprofloxacin/pharmacology , Drug Resistance, Bacterial/genetics , Humans , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests
6.
Mini Rev Med Chem ; 22(22): 2813-2819, 2022.
Article in English | MEDLINE | ID: mdl-35319363

ABSTRACT

Due to their difficulty in pathogenesis, nervous system disease (NSD) therapies have long been challenging problems for researchers. With the rise in the ageing population, the quest for successful NSD therapies has become a hot topic. Polysaccharides demonstrated numerous biological effects in anti-oxidation, anti-inflammation, and immune regulation. In recent years, several studies have been conducted in light of the connection between the properties of polysaccharides and the pathogenesis of neurological conditions. In this review, we aim to discuss the most recent reports on the beneficial properties and mechanisms of polysaccharides for nervous system-related diseases.


Subject(s)
Nervous System Diseases , Humans , Nervous System Diseases/drug therapy , Nervous System Diseases/pathology , Aging , Polysaccharides/pharmacology , Polysaccharides/therapeutic use
7.
Curr Mol Pharmacol ; 15(6): 803-814, 2022.
Article in English | MEDLINE | ID: mdl-35023463

ABSTRACT

COVID-19, which is speedily distributed across the world and presents a significant challenge to public health, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Following MERS coronavirus (MERS-CoV) and SARS, this is the third severe coronavirus outbreak in less than 20 years. To date, there are no exact agents and vaccines available for the treatment of COVID-19 that are clinically successful. Antimicrobial medications are effective in controlling infectious diseases. However, the extensive use of antibiotics makes microbes more resistant to drugs and demands novel bioactive agents' development. Polysaccharides are currently commonly used in the biomedical and pharmaceutical industries for their remarkable applications. Polysaccharides appear to have a wide range of anti-virus (anti-coronavirus) and antimicrobial applications. Polysaccharides are able to induce bacterial cell membrane disruption as they demonstrate potency in binding onto the surfaces of microbial cells. Here, the antiviral mechanisms of such polysaccharides and their success in the application of antiviral infections are reviewed. Additionally, this report provides a summary of current advancements of well-recognized polysaccharides as antimicrobial and anti-biofilm agents.


Subject(s)
COVID-19 Drug Treatment , Viruses , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , SARS-CoV-2
8.
Curr Pharm Biotechnol ; 23(10): 1284-1312, 2022.
Article in English | MEDLINE | ID: mdl-34132178

ABSTRACT

BACKGROUND: Acne is a serious skin problem that affects mostly adolescents. The topical and systematic therapies are effective but could lead to several side effects and the emergence of antibacterial resistance of the acne-causing bacteria. Plant resources have been used as traditional medicine for centuries and can be the alternative therapies for acne treatment. Antioxidants are compounds that can prevent or delay the oxidation of substrates when present in low concentrations. Antioxidants are usually involved in several mechanisms of action, including the inhibition of free radical generation, enhancement of the scavenging capacity against free radicals, and reducing power. METHODS: In this study, three antioxidant assays, DPPH, ABTS, and FRAP were used to evaluate the antioxidant properties of the ethanolic extracts of five plant extracts (A. bilimbi, M. nigra, O. stamineus, P. granatum, and E. longifolia). Furthermore, the study aimed to identify the most potent plant extracts and their combination which could provide better antibacterial activities against acnecausing bacteria. Ethanolic extracts of A. bilimbi, O. stamineus, M. nigra, P. granatum, and E. longifolia were prepared by the Ultrasound-Assisted Extraction (UAE) technique. Their phytochemical contents were screened using several biochemical tests and GC-MS analysis. RESULTS: The study found that only the extracts of P. granatum and O. stamineus exhibited good antioxidant activity using DPPH assay (82.37% and 81.72% µg/mL respectively) and in ABTS assay (87.25% and 88.85% µg/mL respectively); their observed FRAP values were 115.1667 ± 5.6182 and 41.3860 ± 2.4583 µg/mL, respectively. The preliminary antibacterial screening using the disc diffusion method showed that P. granatum and O. stamineus were the most potent extracts; hence, both extracts were combined at the ratios of 1:1, 1:2, and 2:1 to a total concentration of 400 mg/mL. DISCUSSION: The antibacterial efficacy of the mixture was studied using the disc diffusion method and the MIC value was determined. Both S. aureus and S. epidermidis were sensitive to all the individual and combined extracts but C. acnes was resistant to all of them. CONCLUSION: The antibacterial activity of the combined extracts against S. aureus showed a synergistic effect at the ratio of 2:1 with the inhibitory zone diameter of 18.00 ± 1.00 mm and MIC value of 12.5 mg/mL; however, antagonistic effects were observed against S. epidermidis while no effect was noted against C. acnes. Therefore, all the selected plant extracts exhibited antibacterial activities against certain bacteria and their effects may be enhanced by combining the plant extracts.


Subject(s)
Acne Vulgaris , Anti-Infective Agents , Adolescent , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Ethanol/chemistry , Free Radicals , Humans , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/pharmacology , Staphylococcus aureus , Staphylococcus epidermidis
9.
Food Technol Biotechnol ; 59(2): 127-136, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34316274

ABSTRACT

RESEARCH BACKGROUND: Antioxidants are important compounds present at low concentrations that inhibit oxidation processes. Due to the side effects of synthetic antioxidants, research interest has increased considerably towards finding natural sources of antioxidants that can replace the synthetic ones. The emergence and spread of antibiotic resistance require the development of new drugs or some potential sources of novel medicine. This work aims to extract the secondary metabolites of Saccharomyces cerevisiae using ethyl acetate as a solvent and to determine the antioxidant and antimicrobial activities of these extracted metabolites. EXPERIMENTAL APPROACH: The antioxidant activity of the secondary metabolites of S. cerevisiae were determined using DPPH, ABTS and FRAP assays. Furthermore, the antimicrobial potential of the ethyl acetate extract of S. cerevisiae against Cutibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis was assessed. RESULTS AND CONCLUSION: Five out of 13 of the extracted secondary metabolites were identified as antioxidants. The antioxidant activity of the S. cerevisiae extract exhibited relatively high IC50 of 455.26 and 294.51 µg/mL for DPPH and ABTS respectively, while the obtained FRAP value, expressed as ascorbic acid equivalents, was 44.40 µg/mL. Moreover, the extract had a significant antibacterial activity (p<0.05) against Staphylococcus aureus and Staphylococcus epidermidis at the concentrations of 100 and 200 mg/mL, respectively. However, no inhibitory effect was observed against Cutibacterium acnes as the extract was only effective against the bacterium at the concentrations of 300 and 400 mg/mL (inhibition zones ranging from 9.0±0.0 to 9.3±0.6) respectively (p<0.05). Staphylococcus aureus was highly sensitive to the extract, with a MIC value of 18.75 mg/mL. NOVELTY AND SCIENTIFIC CONTRIBUTION: This report confirmed the efficacy of the secondary metabolites of S. cerevisiae as a natural source of antioxidants and antimicrobials and suggested the possibility of employing them in drugs for the treatment of infectious diseases caused by the tested microorganisms.

10.
Pharmacol Rep ; 73(1): 1-16, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32946075

ABSTRACT

The discovery of antibiotics ought to have ended the issue of bacterial infections, but this was not the case as it has led to the evolution of various mechanisms of bacterial resistance against various antibiotics. The efflux pump remains one of the mechanisms through which organisms develop resistance against antibiotics; this is because organisms can extrude most of the clinically relevant antibiotics from the interior cell environment to the exterior environment via the efflux pumps. Efflux pumps are thought to contribute significantly to biofilm formation as highlighted by various studies. Therefore, the inhibition of these efflux pumps can be a potential way of improving the activity of antibiotics, particularly now that the discovery of novel antibiotics is becoming tedious. Efflux pump inhibitors (EPIs) are molecules that can inhibit efflux pumps; they have been considered potential therapeutic agents for rejuvenating the activity of antibiotics that have already lost their activity against bacteria. However, studies are yet to determine the specific substrates for such pumps; the effect of altered efflux activity of these pumps on biofilm formation is still being investigated. A clear knowledge of the involvement of efflux pumps in biofilm development could aid in developing new agents that can interfere with their function and help to prevent biofilms formation; thereby, improving the outcome of treatment strategies. This review focuses on the novel update of EPIs and discusses the evidence of the roles of efflux pumps in biofilm formation; the potential approaches towards overcoming the increasing problem of biofilm-based infections are also discussed.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Membrane Transport Proteins/drug effects , Animals , Bacteria/drug effects , Biofilms/drug effects , Humans
11.
Mini Rev Med Chem ; 20(18): 1908-1916, 2020.
Article in English | MEDLINE | ID: mdl-32811410

ABSTRACT

The need for new therapeutics and drug delivery systems has become necessary owing to the public health concern associated with the emergence of multidrug-resistant microorganisms. Among the newly discovered therapeutic agents is cefiderocol, which was discovered by Shionogi Company, Japan as an injectable siderophore cephalosporin. Just like the other ß-lactam antibiotics, cefiderocol exhibits antibacterial activity via cell wall synthesis inhibition, especially in Gram negative bacteria (GNB); it binds to the penicillin-binding proteins, but its unique attribute is that it crosses the periplasmic space of bacteria owing to its siderophore-like attribute; it also resists the activity of ß-lactamases. Among all the synthesized compounds with the modified C-7 side chain, cefiderocol (3) presented the best and well-balanced activity against multi-drug resistant (MDR) Gram negative bacteria, including those that are resistant to carbapenem. In this article, an overview of the recent studies on cefiderocol was presented.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cephalosporins/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Gram-Negative Bacteria/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cephalosporins/chemical synthesis , Cephalosporins/chemistry , Microbial Sensitivity Tests , Molecular Structure , Cefiderocol
12.
Curr Drug Targets ; 21(13): 1326-1343, 2020.
Article in English | MEDLINE | ID: mdl-32564749

ABSTRACT

Iron, which is described as the most basic component found in nature, is hard to be assimilated by microorganisms. It has become increasingly complicated to obtain iron from nature as iron (II) in the presence of oxygen oxidized to press (III) oxide and hydroxide, becoming unsolvable at neutral pH. Microorganisms appeared to produce organic molecules known as siderophores in order to overcome this condition. Siderophore's essential function is to connect with iron (II) and make it dissolvable and enable cell absorption. These siderophores, apart from iron particles, have the ability to chelate various other metal particles that have collocated away to focus the use of siderophores on wound care items. There is a severe clash between the host and the bacterial pathogens during infection. By producing siderophores, small ferric iron-binding molecules, microorganisms obtain iron. In response, host immune cells produce lipocalin 2 to prevent bacterial reuptake of siderophores loaded with iron. Some bacteria are thought to produce lipocalin 2-resistant siderophores to counter this risk. The aim of this article is to discuss the recently described roles and applications of bacterial siderophore.


Subject(s)
Bacteria/metabolism , Siderophores/biosynthesis , Siderophores/physiology , Animals , Anti-Bacterial Agents/chemistry , Host-Pathogen Interactions , Humans , Iron/metabolism , Lipocalin-2/metabolism , Mitophagy , Siderophores/chemistry , Siderophores/therapeutic use , beta-Lactams/chemistry
13.
Article in English | MEDLINE | ID: mdl-31595857

ABSTRACT

BACKGROUND: Numerous investigations demonstrate efflux as a worldwide bacterial mode of action which contributes to the resistance of drugs. The activity of antibiotics, which subjects to efflux, can be improved by the combined usage of efflux inhibitors. However, the efflux role to the overall levels of antibiotic resistance of clinical M. tuberculosis isolates is inadequately comprehended and is still disregarded by many. METHODS: Here, we assessed the contribution of resistant genes associated with isoniazid (INH) and rifampin (R) resistance to the levels of drug resistance in the (27) clinical isolates of MDR-TB. Additionally, the role of the resistance for six putative drug efflux pump genes to the antibiotics was investigated. The level of katG expression was down-regulated in 24/27 (88.88%) of MDR-TB isolates. Of the 27 MDR-TB isolates, inhA, oxyR-ahpC, and rpoB showed either overexpression or up-regulation in 8 (29.62%), 4 (14.81 %), and 24 (88.88%), respectively. Moreover, the efflux pump genes drrA, drrB, efpA, Rv2459, Rv1634, and Rv1250 were overexpressed under INH/RIF plus fresh pomegranate juice (FPJ) stress signifying the efflux pumps contribution to the overall levels of the resistance of MDR-TB isolates. CONCLUSION: These results displayed that the levels of drug resistance of MDR-TB clinical isolates are due to combination among drug efflux pump and the presence of mutations in target genes, a truth which is often ignored by the specialists of tuberculosis in favour of the almost undoubted significance of drug target- gene mutations for the resistance in M. tuberculosis.


Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Tuberculosis, Multidrug-Resistant/genetics , Antitubercular Agents/therapeutic use , Gene Expression Regulation , Humans , Isoniazid/pharmacology , Isoniazid/therapeutic use , Mycobacterium tuberculosis/isolation & purification , Rifampin/pharmacology , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy
14.
Curr Pharm Biotechnol ; 20(4): 317-326, 2019.
Article in English | MEDLINE | ID: mdl-30854955

ABSTRACT

BACKGROUND: The global rise of multi-drug resistant M. tuberculosis demands unconventional treatment to enhance the efficiency of current drugs. Punica granatum, which is known as pomegranate, is considered as a member of the Punicaceae family. Pomegranate, which is broadly documented for its activity against a wide spectrum of bacterial pathogens, deserves further scrutiny in this respect. METHODS: Within this scope, this study investigated the effect of fresh pomegranate juice (FPJ) on the antibacterial activity of anti-tuberculosis drugs (Rifampin (R) and Isoniazid (INH)) against MDR-TB clinical isolates. The drug resistance profiles in M. tuberculosis clinical isolates were determined by susceptibility test using BACTEC MGIT 960 system. Four concentrations of fresh pomegranate juice (FPJ) (5%, 10%, 15%, and 20%) were evaluated in combination with R and INH at a dose range of (1.0 µg/ml) and (0.1 µg/ml), respectively against the MDR-TB isolates by the BACTEC MGIT 960 system. Moreover, this study scrutinized individual phenolic compounds of FPJ by using highperformance liquid chromatography (HPLC). The total polyphenols (TP), total flavonoid (TF), total anthocyanins content (TAC), and the antioxidant capacity were also assessed in FPJ. RESULTS: Synergistic effects were observed between R and INH with FPJ against all tested strains. However, combination therapy of rifampin was more effective than isoniazid one. Therefore, the combination of R and FPJ has been used against (27) MDR-TB clinical isolates. 5% of FPJ plus R (1.0 µg/ml) were found to suppress the growth of one isolates for first group (INH and R resistant). However, 5% of FPJ demonstrated no synergistic impact with R for second (SM, R and INH resistant) and third group (INH, EMB, R and SM resistant). Moreover, 10% of FPJ and R (1.0 µg/ml) inhibited the bacterial growth of three isolates of first group and two isolates and one isolate for second and third group, respectively. Remarkably, 15% of FPJ plus R (1.0 µg/ml) appeared to inhibit the growth of MDR-TB isolates for all tested groups indicating a strong synergistic effect. Regarding H37RV, the complete inhibition of the bacterial growth was found to occur at 15% and 20% concentrations of FPJ only. Minimum inhibitory concentration (MIC) of FPJ ranged from (4% to13%) for first group and from (10% to15%) for second and third group. Thus, FPJ at 15% inhibited 100% of bacteria for all tested isolates (MIC100% =15%). Phenolic compounds identified in FPJ were gallic acid, benzoic acid, syringic, folic acid, pelargonidin, naringin+ellagic acid, naringenin, chlorogenic acid, caffeic acid, catechin, myricetin, kaempferol, quercetin, cyanidin-3-glycoside, p-cummaric acid, ferulic acid, and rutin. Total phenolic (TP), total flavonoid (TF), and total anthocyanin (TA) content were 841.5 mg/L, 638.73 mg RE/L, and 47.43 mg/L, accordingly. CONCLUSION: Overall, FPJ displayed synergistic effect with R against MDR-TB clinical isolates due to its high content of polyphenol and antioxidant capability.


Subject(s)
Antitubercular Agents/pharmacology , Lythraceae/chemistry , Mycobacterium tuberculosis/drug effects , Polyphenols/pharmacology , Rifampin/pharmacology , Tuberculosis, Multidrug-Resistant/microbiology , Antitubercular Agents/administration & dosage , Drug Resistance, Multiple, Bacterial/drug effects , Fruit and Vegetable Juices/analysis , Humans , Isoniazid/administration & dosage , Isoniazid/pharmacology , Microbial Sensitivity Tests , Mycobacterium tuberculosis/isolation & purification , Polyphenols/administration & dosage , Rifampin/administration & dosage
15.
Curr Mol Pharmacol ; 12(2): 83-104, 2019.
Article in English | MEDLINE | ID: mdl-30474542

ABSTRACT

BACKGROUND: Mycobacterium tuberculosis (Mtb) is considered as one of the most efficacious human pathogens. The global mortality rate of TB stands at approximately 2 million, while about 8 to 10 million active new cases are documented yearly. It is, therefore, a priority to develop vaccines that will prevent active TB. The vaccines currently used for the management of TB can only proffer a certain level of protection against meningitis, TB, and other forms of disseminated TB in children; however, their effectiveness against pulmonary TB varies and cannot provide life-long protective immunity. Based on these reasons, more efforts are channeled towards the development of new TB vaccines. During the development of TB vaccines, a major challenge has always been the lack of diversity in both the antigens contained in TB vaccines and the immune responses of the TB sufferers. Current efforts are channeled on widening both the range of antigens selection and the range of immune response elicited by the vaccines. The past two decades witnessed a significant progress in the development of TB vaccines; some of the discovered TB vaccines have recently even completed the third phase (phase III) of a clinical trial. OBJECTIVE: The objectives of this article are to discuss the recent progress in the development of new vaccines against TB; to provide an insight on the mechanism of vaccine-mediated specific immune response stimulation, and to debate on the interaction between vaccines and global interventions to end TB.


Subject(s)
Bacterial Vaccines/immunology , Tuberculosis/prevention & control , Bacterial Proteins/immunology , Bacterial Proteins/metabolism , Humans , Immune System/metabolism , Mycobacterium tuberculosis/immunology , Nanoparticles/chemistry , Recombinant Fusion Proteins/immunology , Tuberculosis/immunology , Tuberculosis/pathology , Vaccines, Subunit/immunology , Vesiculovirus/genetics , Vesiculovirus/metabolism
16.
Pharmacol Rep ; 70(2): 217-226, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29475004

ABSTRACT

Tuberculosis (TB) is described as lethal disease in the world. Resistant to TB drugs is the main reason to have unfavourable outcomes in the treatment of TB. Therefore, new agents to replace existing drugs are urgently needed. Previous reports suggested that InhA inhibitors, an enoyl-ACP-reductase, might provide auspicious candidates which can be developed into novel antitubercular agents. In this review, we explain the role of InhA in the resistance of isoniazid. Furthermore, five classes of InhA inhibitors, which display novel binding modes and deliver evidence of their prosperous target engagement, have been debated.


Subject(s)
Antitubercular Agents/therapeutic use , Inhibins/antagonists & inhibitors , Tuberculosis/drug therapy , Drug Resistance, Bacterial/drug effects , Humans , Isoniazid/therapeutic use , Tuberculosis/metabolism
17.
Mini Rev Med Chem ; 18(6): 507-526, 2018.
Article in English | MEDLINE | ID: mdl-28425868

ABSTRACT

Four distinguished although overlying stages make up the methodical procedure of wound healing, which are hemostasis, inflammation, proliferation and remodelling. Multiple sclerosis (MS) is described as an incessant inflammatory central nervous system disease, and is linked with neurodegeneration, demyelination, as well as susceptibility to oxidative pressure. Obesity signifies a swiftly developing danger to the wellbeing of populations in a rising number of nations. Usually called diabetes mellitus (DM) by medical practitioners, diabetes details a collection of metabolic diseases within which the individual has raised blood glucose, either due to an insufficiency of insulin generation, or the lack of suitable response by the body to insulin, or both. Conventionally, the pomegranate, as well as its flowers, leaves, fruit juice and tree bark, has been applied in the treatment of conditions including acidosis, haemorrhage, diarrhoea and microbial contagions. Extracts of pomegranate have been established to contain intense anti-inflammatory, antioxidant as well as antitumor features in vivo as well as ex vivo. Of late, beneficial consequences of decrease of fat have been illustrated employing the pomegranate as well as its extracts. Several of the favourable consequences are associated with the availability of anthocyanins, tannins, and considerably elevated amounts of antioxidants, as well as flavonoids and polyphenols. A summary of the endeavours applied to deal with the possible advantages of the pomegranate towards healing wounds, Alzheimer's disease (AD), diabetes mellitus (DM) and obesity, as well as an appraisal of the efficiency of intervention through the pomegranate and its extracts is provided in this article.


Subject(s)
Diabetes Mellitus/drug therapy , Lythraceae , Neurodegenerative Diseases/drug therapy , Obesity/drug therapy , Plant Extracts/therapeutic use , Wound Healing/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/therapeutic use , Antioxidants/chemistry , Antioxidants/therapeutic use , Fruit/chemistry , Humans , Hydrolyzable Tannins/chemistry , Hydrolyzable Tannins/therapeutic use , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/therapeutic use , Lythraceae/chemistry , Plant Extracts/chemistry
18.
Curr Drug Deliv ; 15(4): 470-484, 2018.
Article in English | MEDLINE | ID: mdl-29219055

ABSTRACT

BACKGROUND: Until recently, one of the main reasons for mortality has been infectious diseases, and bacteria that are drug-resistant have emerged as a result of the wide application, as well as the misuse of antibacterial medications. Having multidrug-resistance, bacteria present a great problem for the efficient management of bacterial infections and this challenge has resulted in the creation of other means of dealing with bacterial diseases. Of late, metallic nanoparticles (NPs), employed as antibacterial agents, have the potential for use against resistance to bacterial drugs. OBJECTIVE: The mechanisms of bacterial resistance are described in this review and this is followed by an outline of the features and uses of metallic NPs as antibiotic agents to address bacteria that are antibiotic- sensitive and resistant. Additionally, a general impression of metallic NPs as antibiofilm bactericidal agents is presented. CONCLUSION: Biofilms and bacterial strains that are resistant to antibiotics present a grave public health challenge and this has enhanced the need to develop new bactericidal agents. Therefore, nanomaterials are considered as a potential platform for managing bacterial infections.


Subject(s)
Biofilms/drug effects , Drug Carriers/therapeutic use , Drug Resistance, Multiple, Bacterial/drug effects , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/therapeutic use , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/therapeutic use , Drug Carriers/pharmacology , Humans , Metal Nanoparticles/adverse effects
19.
Pharmacol Res ; 128: 288-305, 2018 02.
Article in English | MEDLINE | ID: mdl-29079429

ABSTRACT

Tuberculosis (TB) presently accounts for high global mortality and morbidity rates, despite the introduction four decades ago of the affordable and efficient four-drugs (isoniazid, rifampicin, pyrazinamide and ethambutol). Thus, a strong need exists for new drugs with special structures and uncommon modes of action to effectively overcome M. tuberculosis. Within this scope, antimicrobial peptides (AMPs), which are small, cationic and amphipathic peptides that comprise a section of the innate immune system, are currently the leading potential agents for the treatment of TB. Many studies have recently illustrated the capability of anti-mycobacterial peptides to disrupt the normal mycobacterial cell wall function through various modes, thereby interacting with the intracellular targets, as well as encompassing nucleic acids, enzymes and organelles. This review presents a wide array of antimicrobial activities, alongside the associated properties of the AMPs that could be utilized as potential agents in therapeutic tactics for TB treatment.


Subject(s)
Antimicrobial Cationic Peptides/therapeutic use , Antitubercular Agents/therapeutic use , Tuberculosis/drug therapy , Animals , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Drug Delivery Systems , Humans , Mycobacterium/drug effects
20.
Biomed Pharmacother ; 91: 546-558, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28482292

ABSTRACT

Tuberculosis presents a grave challenge to health, globally instigating 1.5 million mortalities each year. Following the breakthrough of first-line anti-TB medication, the number of mortalities reduced greatly; nonetheless, the swift appearance of tuberculosis which was drug-resistant, as well as the capability of the bacterium to survive and stay dormant are a considerable problem for public health. In order to address this issue, several novel possible candidates for tuberculosis therapy have been subjected to clinical trials of late. The novel antimycobacterial agents are acquired from different categories of medications, operate through a range of action systems, and are at various phases of advancement. We therefore talk about the present methods of treating tuberculosis and novel anti-TB agents with their action method, in order to advance awareness of these new compounds and medications.


Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/physiology , Tuberculosis/drug therapy , Tuberculosis/microbiology , Animals , Antitubercular Agents/pharmacology , Drug Delivery Systems , Drug Repositioning , Humans , Mycobacterium tuberculosis/drug effects , RNA, Antisense/therapeutic use
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