Aminoglycosides with anti-MRSA activity: A concise review

2021 ◽  
Vol 21 ◽  
Author(s):  
Cheng-Jiao Yao ◽  
Yi-lin Li ◽  
Meng-Jun Pu ◽  
Li-Hong Luo ◽  
Qin Xiong ◽  
...  
Keyword(s):  
Rational Design ◽  
Multidrug Resistant ◽  
Medical Field ◽  
Drug Candidates ◽  
Concise Review ◽  
Current Scenario ◽  
Potential Activity ◽  
Gram Negative Organisms ◽  
Systemic Infections ◽  
Significant Health

: Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti-MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

Current scenario of acridine hybrids with anticancer potential

2021 ◽  
Vol 21 ◽  
Author(s):  
Qihong Zhang ◽  
Xia Yu
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Rational Design ◽  
Complex Disease ◽  
Single Agent ◽  
Drug Candidates ◽  
Cycle Arrest ◽  
Current Scenario ◽  
Potential Activity ◽  
Almost All

: Cancer, a complex disease which involves abnormalities of multiple cellular pathways, is one of the most serious threatens to human health across the world. Chemotherapy with a single agent or a combined regimen is a standardized strategy for the treatment of almost all human cancers, and the cure rate of cancer increases with the continuous discovery of anticancer agents and the optimization of chemotherapy options. However, drug resistance especially multidrug resistance remains an obstacle in the effective treatment of cancer. Hence, it is urgent to develop novel agents with potential activity against cancers, especially drug-resistant forms. Acridine, which bears three fused rings, could intercalate into DNA and interfere with metabolic processes. Recently, acridines have been found with anticancer activity in a variety of malignancies through suppressing cell proliferation, stimulating apoptosis, and inducing cell cycle arrest, retarding migration, invasion and metastasis. Thus, acridines are useful scaffolds for the discovery of novel drug candidates with potent anticancer activity. This review focused on the current scenario of acridine hybrids with potential activity against cancers reported from Jan. 2015 to Feb. 2021. The mechanisms of action, the criteria of compound design as well as structure-activity relationships were also summarized to pave the way for further rational design of novel anticancer agents.

Chalcone derivatives and their activities against drug-resistant cancers: An overview

2020 ◽  
Vol 20 ◽  
Author(s):  
Jiaqi Xiao ◽  
Meixiang Gao ◽  
Qiang Diao ◽  
Feng Gao
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Rational Design ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Chalcone Derivatives ◽  
Potential Activity ◽  
Defensive Mechanisms

: Drug resistance including multidrug resistance resulting from different defensive mechanisms in cancer cells is the leading cause of the failure about the cancer therapy, making it an urgent need to develop more effective anticancer agents. Chalcones, widely distributed in nature, could act on diverse enzymes and receptors in cancer cells. Accordingly, chalcone derivatives possess potential activity against various cancers including drug-resistant even multidrug-resistant cancer. This review outlines the recent development of chalcone derivatives with potential activity against drug-resistant cancers covering articles published between 2010 and 2020, so as to facilitate further rational design of more effective candidate.

Triazole-containing hybrids with anti-Mycobacterium tuberculosis potential – Part I: 1,2,3-Triazole

2021 ◽  
Author(s):  
Zhenyou Tan ◽  
Jun Deng ◽  
Qiongxian Ye ◽  
Zhenfeng Zhang
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Rational Design ◽  
Multidrug Therapy ◽  
Resistance Development ◽  
Drug Candidates ◽  
Structure Activity ◽  
Privileged Structure ◽  
Potential Part ◽  
Potential Activity

Tuberculosis regimens currently applied in clinical practice require months of multidrug therapy, which imposes a major challenge of patient compliance and drug resistance development. Moreover, because of the increasing emergence of hard-to-treat tuberculosis, this disease continues to be a significant threat to the human population. 1,2,3-triazole as a privileged structure has been widely used as an effective template for drug discovery, and 1,2,3-triazole-containing hybrids that can simultaneously act on dual or multiple targets in Mycobacterium tuberculosis have the potential to circumvent drug resistance, enhance efficacy, reduce side effects and improve pharmacokinetic as well as pharmacodynamic profiles. Thus, 1,2,3-triazole-containing hybrids are useful scaffolds for the development of antitubercular agents. This review aims to highlight recent advances of 1,2,3-triazole-containing hybrids with potential activity against various forms of M. tuberculosis, covering articles published between 2015 and 2020. The structure–activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective drug candidates.

scholarly journals Intravenous Fosfomycin: An Assessment of Its Potential for Use in the Treatment of Systemic Infections in Canada

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
George G. Zhanel ◽  
Michael A. Zhanel ◽  
James A. Karlowsky
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Hospitalized Patients ◽  
Second Line ◽  
Pharmacological Interactions ◽  
Term Administration ◽  
Excellent Safety Profile ◽  
Tract Infections ◽  
Systemic Infections

Fosfomycin is a bactericidal agent that inhibits cell wall synthesis using a mechanism of action distinct from β-lactams or other antimicrobial agents. It is a broad-spectrum agent that is frequently active against antimicrobial-resistant bacterial pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Enterobacteriaceae, and some isolates of MDR Pseudomonas aeruginosa. Intravenous fosfomycin has been prescribed for a wide variety of infections in many countries for >40 years. It is most frequently used in combination with other antimicrobial agents (e.g., β-lactams, carbapenems, and aminoglycosides) and has an excellent safety profile, including in neonates and children, even with long-term administration (weeks). Fosfomycin achieves extensive tissue distribution including difficult to reach compartments such as aqueous humor, vitreous humor, abscess fluid, and CSF. Available data, to date, suggest no clinically relevant pharmacological interactions between fosfomycin and other agents, including drugs, stimulants, or food. Intravenous fosfomycin’s role in therapy in Canada is likely as an agent used alone or in combination for complicated urinary tract infections in hospitalized patients as well as hospitalized patients with MDR infections who have not responded to first-, and potentially, second-line antimicrobials or in patients who cannot tolerate (due to adverse effects) first- and second-line antimicrobials.

scholarly journals Prediction of Minocycline Activity in the Gut From a Pig Preclinical Model Using a Pharmacokinetic -Pharmacodynamic Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Quentin Vallé ◽  
Béatrice B. Roques ◽  
Alain Bousquet-Mélou ◽  
David Dahlhaus ◽  
Felipe Ramon-Portugal ◽  
...  
Keyword(s):  
Intestinal Content ◽  
Multidrug Resistant ◽  
Preclinical Model ◽  
Intestinal Contents ◽  
Potential Activity ◽  
Potential Impact ◽  
The Impact ◽  
Pharmacodynamic Approach

The increase of multidrug-resistant (MDR) bacteria has renewed interest in old antibiotics, such as minocycline, that can be active against various MDR Gram-negative pathogens. The elimination of minocycline by both kidneys and liver makes it suitable for impaired renal function patients. However, the drawback is the possible elimination of a high amount of drug in the intestines, with potential impact on the digestive microbiota during treatment. This study aimed to predict the potential activity of minocycline against Enterobacterales in the gut after parenteral administration, by combining in vivo and in vitro studies. Total minocycline concentrations were determined by UPLC-UV in the plasma and intestinal content of piglets following intravenous administration. In parallel, the in vitro activity of minocycline was assessed against two Escherichia coli strains in sterilized intestinal contents, and compared to activity in a standard broth. We found that minocycline concentrations were 6–39 times higher in intestinal contents than plasma. Furthermore, minocycline was 5- to 245-fold less active in large intestine content than in a standard broth. Using this PK-PD approach, we propose a preclinical pig model describing the link between systemic and gut exposure to minocycline, and exploring its activity against intestinal Enterobacterales by taking into account the impact of intestinal contents.

scholarly journals Molecular Characterization of Isolated Multidrug-Resistant Bacteria from Tertiary Care Hospitals of Ahmedabad: A Comparison Study Between Previous to COVID-19 and Current Scenario

2021 ◽  
Author(s):  
Anurag D. Zaveri ◽  
Dilip N. Zaveri ◽  
Lakshmi Bhaskaran
Keyword(s):  
Molecular Characterization ◽  
Tertiary Care ◽  
Future Generation ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
E Coli ◽  
Pseudomonas Spp ◽  
Bacillus Spp ◽  
Current Scenario ◽  
Klebsiella Spp

Hospital Acquired Infections (HAIs) are a significant concern for healthcare setups, as it increases the overall cost of treatment, patients stay in hospitals, making them susceptible to secondary and tertiary infections and, sometimes, mortality1. To prevent or control HAIs, evaluating the organisms isolated from the critically maintained areas is considered of epitome importance and everlasting practice in the healthcare industry. Identifying such organisms and screening them for antibiotic resistance is mandatory, but it also helps professionals understand colonization trends. Sensitive areas of healthcare setups were screened monthly from years 2017 to 2020. A total of 4400 samples of hospital hygiene, e.g., intravenous drip stands, ventilator surface, anesthetist’s trolley, patient’s bed, instrument trolley, etcetera, were collected. Isolated organisms were cultured and screened using the CLSI technique. E. coli, Pseudomonas spp., and Klebsiella spp. were found in both previous to COVID current samples. Multidrug-resistant organisms were subjected to molecular characterization to detect the presence of carbapenem genes. Evaluation data of both pre-and during Coronavirus Disease or COVID-19 were compared. The prevalence of pathogenic (Klebsiella spp., E. coli, and Pseudomonas spp.) and non-pathogenic (Staphylococcus aureus and Bacillus spp.) strains in healthcare setups decreased drastically (Klebsiella spp. from 80% to 20%, E.coli from 90% to 10% and Pseudomonas spp. from 80% to 20%). It is possible only because of the awareness in non-specialists and healthcare workers due to the unforeseen critical situation proving to be a blessing for the future generation.

scholarly journals In Vitro Antibacterial Activity of Selected Palestinian Medicinal Plants against Chlamydia trachomatis

2021 ◽  
Vol 12 (3) ◽  
pp. 656-662
Author(s):  
Omar Hamarsheh ◽  
Ahmad Amro ◽  
Munir A. Al-Zeer
Keyword(s):  
Plant Extracts ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
World Health ◽  
Chlamydia Infection ◽  
Drug Candidates ◽  
Cell Defense ◽  
Wide Range ◽  
Alternative Drug

Chlamydia spp. are intracellular pathogens of humans and animals that cause a wide range of diseases such as blinding trachoma and sexually transmitted infections. According to the World Health Organization (WHO), there are more than 127 million new infections each year worldwide. Chlamydial urogenital infections can cause cervicitis, urethritis, pelvic inflammatory disease and infertility. From within an intracellular niche, termed an inclusion, the Chlamydiae complete their life cycle shielded from host defenses. The host cell defense response used to eliminate the pathogen must subvert this protective shield and is thought to involve the gamma interferon-inducible family of immunity related GTPase proteins and nitric oxide. Typically, azithromycin and doxycycline are the first line drugs for the treatment of chlamydial infections. Although C. trachomatis is sensitive to these antibiotics in vitro, currently, there is increasing bacterial resistance to antibiotics including multidrug-resistant C. trachomatis, which have been described in many instances. Therefore, alternative drug candidates against Chlamydia should be assessed in vitro. In this study, we tested and quantified the activity of plant extracts against Chlamydia-infected HeLa cells with C. trachomatis inclusions. The in vitro results show that post-treatment with Artemisia inculta Delile extract significantly inhibits Chlamydia infection compared to DMSO-treated samples. In conclusion, plant extracts may contain active ingredients with antichlamydial activity potential and can be used as alternative drug candidates for treatment of Chlamydia infection which has significant socio-economic and medical impact.

scholarly journals Molecular Hybridization as a Tool in the Design of Multi-target Directed Drug Candidates for Neurodegenerative Diseases

2020 ◽  
Vol 18 (5) ◽  
pp. 348-407 ◽  
Author(s):  
Vanessa Silva Gontijo ◽  
Flávia P. Dias Viegas ◽  
Cindy Juliet Cristancho Ortiz ◽  
Matheus de Freitas Silva ◽  
Caio Miranda Damasio ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Rational Design ◽  
Brain Regions ◽  
Molecular Hybridization ◽  
Drug Candidate ◽  
New Paradigm ◽  
New Approach ◽  
Biological Targets ◽  
Drug Candidates ◽  
Biochemical Pathways

Neurodegenerative Diseases (NDs) are progressive multifactorial neurological pathologies related to neuronal impairment and functional loss from different brain regions. Currently, no effective treatments are available for any NDs, and this lack of efficacy has been attributed to the multitude of interconnected factors involved in their pathophysiology. In the last two decades, a new approach for the rational design of new drug candidates, also called multitarget-directed ligands (MTDLs) strategy, has emerged and has been used in the design and for the development of a variety of hybrid compounds capable to act simultaneously in diverse biological targets. Based on the polypharmacology concept, this new paradigm has been thought as a more secure and effective way for modulating concomitantly two or more biochemical pathways responsible for the onset and progress of NDs, trying to overcome low therapeutical effectiveness. As a complement to our previous review article (Curr. Med. Chem. 2007, 14 (17), 1829-1852. https://doi.org/10.2174/092986707781058805), herein we aimed to cover the period from 2008 to 2019 and highlight the most recent advances of the exploitation of Molecular Hybridization (MH) as a tool in the rational design of innovative multifunctional drug candidate prototypes for the treatment of NDs, specially focused on AD, PD, HD and ALS.

scholarly journals Hospital-acquired infections due to multidrug-resistant organisms in Hungary, 2005-2010

2013 ◽  
Vol 18 (2) ◽  
Author(s):  
S Caini ◽  
A Hajdu ◽  
A Kurcz ◽  
K Böröcz
Keyword(s):  
Infection Control ◽  
Multidrug Resistant ◽  
Special Focus ◽  
Gram Negative ◽  
Hospital Acquired Infections ◽  
Health Authorities ◽  
Multidrug Resistant Organisms ◽  
Public Health Authorities ◽  
Gram Negative Organisms ◽  
Hospital Acquired

Healthcare-associated infections caused by multidrug-resistant organisms are associated with prolonged medical care, worse outcome and costly therapies. In Hungary, hospital-acquired infections (HAIs) due to epidemiologically important multidrug-resistant organisms are notifiable by law since 2004. Overall, 6,845 case-patients (59.8% men; median age: 65 years) were notified in Hungary from 2005 to 2010. One third of case-patients died in hospital. The overall incidence of infections increased from 5.4 in 2005 to 14.7 per 100,000 patient-days in 2010. Meticillin-resistant Staphylococcus aureus (MRSA) was the most frequently reported pathogen (52.2%), but while its incidence seemed to stabilise after 2007, notifications of multidrug-resistant Gram-negative organisms have significantly increased from 2005 to 2010. Surgical wound and bloodstream were the most frequently reported sites of infection. Although MRSA incidence has seemingly reached a plateau in recent years, actions aiming at reducing the burden of HAIs with special focus on Gram-negative multidrug-resistant organisms are needed in Hungary. Continuing promotion of antimicrobial stewardship, infection control methodologies, reinforced HAI surveillance among healthcare and infection control practitioners, and engagement of stakeholders, hospital managers and public health authorities to facilitate the implementation of existing guidelines and protocols are essential.

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