[ASAP] Second Generation of Zafirlukast Derivatives with Improved Activity against the Oral Pathogen < italic toggle="yes" > Porphyromonas gingivalis < /italic >
ACS Medicinal Chemistry LettersDOI: 10.1021/acsmedchemlett.9b00614 (Source: ACS Medicinal Chemistry Letters)
Source: ACS Medicinal Chemistry Letters - March 18, 2020 Category: Chemistry Authors: Kaitlind C. Howard †, Octavio A. Gonzalez*‡§, and Sylvie Garneau-Tsodikova*† Source Type: research
MK-571, a cysteinyl leukotriene receptor-1 antagonist, inhibits hepatitis C virus (HCV) replication.
In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.
PMID: 32179525 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - March 15, 2020 Category: Microbiology Authors: Ruiz I, Nevers Q, Hernández E, Ahnou N, Brillet R, Softic L, Donati F, Berry F, Hamadat S, Fourati S, Pawlotsky JM, Ahmed-Belkacem A Tags: Antimicrob Agents Chemother Source Type: research
Small scale design of experiment investigation of equilibrium solubility in simulated fasted and fed intestinal fluid.
Abstract
It is widely recognised that drug solubility within the gastrointestinal tract (GIT) differs from values determined in a simple aqueous buffer and to circumvent this problem measurement in biorelevant fluids is determined. Biorelevant fluids are complex mixtures of components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pancreatin and sodium oleate) at various concentrations and pH levels to provide systems simulating fasted (FaSSIF) or fed (FeSSIF) intestinal media. Design of Experiment (DoE) studies have been applied to investigate FaSSIF and FeSSIF and indicate that a drug...
Source: European Journal of Pharmaceutics and Biopharmaceutics - February 5, 2020 Category: Drugs & Pharmacology Authors: McPherson S, Perrier J, Dunn C, Khadra I, Davidson S, Ainousah B, Wilson CG, Halbert G Tags: Eur J Pharm Biopharm Source Type: research
The Role of Leukotrienes Inhibitors in the Management of Chronic Inflammatory Diseases.
CONCLUSION: Present study highlights recent updates on the pharmacology and patents on leukotriene antagonists in the management of inflammation respiratory diseases.
PMID: 32000655 [PubMed - as supplied by publisher] (Source: Recent Patents on Inflammation and Allergy Drug Discovery)
Source: Recent Patents on Inflammation and Allergy Drug Discovery - February 1, 2020 Category: Allergy & Immunology Tags: Recent Pat Inflamm Allergy Drug Discov Source Type: research
Reveal the interaction mechanism of five old drugs targeting VEGFR2 through computational simulations
Publication date: Available online 16 January 2020Source: Journal of Molecular Graphics and ModellingAuthor(s): Yonghui Lv, Yu Wang, Xin Zheng, Guizhao LiangAbstractVEGFR2, vascular endothelial growth factor receptor 2, plays an important role in anti-angiogenesis and is an effective target for inhibiting tumor cell proliferation and metastasis. Many small molecule inhibitors have so far exhibited fine therapeutic effects but do not rule out some adverse reactions. From the perspective of the new use of old drugs, we use a combination of two different docking methods, molecular dynamics simulations and quantum-chemical cal...
Source: Journal of Molecular Graphics and Modelling - January 17, 2020 Category: Molecular Biology Source Type: research
Zafirlukast protects blood-brain barrier integrity from ischemic brain injury
Publication date: Available online 6 December 2019Source: Chemico-Biological InteractionsAuthor(s): Chaosheng Zeng, Desheng Wang, Cong Chen, Lin Chen, Bocan Chen, Li Li, Min Chen, Huaijie XingAbstractStroke has been considered the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Some of the main features of ischemic stroke are increased brain permeability, ischemia/reperfusion injury, oxidative stress, and acute inflammation. Antagonism of cysLT1R has been shown to provide cardiovascular and neural benefits. In the present study, we investigated the effects of the...
Source: Chemico Biological Interactions - December 7, 2019 Category: Biochemistry Source Type: research
Zafirlukast protects blood-brain barrier integrity from ischemic brain injury.
Abstract
Stroke has been considered the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Some of the main features of ischemic stroke are increased brain permeability, ischemia/reperfusion injury, oxidative stress, and acute inflammation. Antagonism of cysLT1R has been shown to provide cardiovascular and neural benefits. In the present study, we investigated the effects of the cysLT1R antagonist zafirlukast both in vivo and in vitro using a middle cerebral artery occlusion (MCAO) mouse model and human brain microvascular endothelial cells (HBMVECs...
Source: Chemico-Biological Interactions - December 5, 2019 Category: Molecular Biology Authors: Zeng C, Wang D, Chen C, Chen L, Chen B, Li L, Chen M, Xing H Tags: Chem Biol Interact Source Type: research
Zafirlukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Reduces the Effect of Advanced Glycation End-Products in Rat Renal Mesangial Cells In Vitro.
CONCLUSIONS Zafirlukast, a CysLTR1 antagonist, reduced the levels of inflammatory cytokines, markers of oxidative stress, and cell apoptosis induced by AGE in mesangial cells in a dose-dependent way. Future in vivo studies are needed to investigate the potential role for zafirlukast in models of diabetic nephropathy.
PMID: 31745068 [PubMed - in process] (Source: Medical Science Monitor)
Source: Medical Science Monitor - November 22, 2019 Category: Research Tags: Med Sci Monit Source Type: research
Dual farnesoid X receptor/soluble epoxide hydrolase modulators derived from Zafirlukast.
Abstract
The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non-alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti-NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti-asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead d...
Source: ChemMedChem - October 30, 2019 Category: Chemistry Authors: Schierle S, Helmstädter M, Schmidt J, Hartmann M, Horz M, Kaiser A, Weizel L, Heitel P, Proschak A, Hernandez-Olmos V, Proschak E, Merk D Tags: ChemMedChem Source Type: research
Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis
Publication date: Available online 9 October 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Pranesh Kumar, Aakriti Agarwal, Ashok K. Singh, Anurag Kumar Gautam, Sreemoyee Chakraborti, Umesh Kumar, Dinesh Kumar, Bolay Bhattacharya, Parthasarathi Panda, Biswajit Saha, Tabish Qidwai, Biswanath Maity, Sudipta SahaAbstractHepatocellular carcinoma (HCC) is one of the most common cancers worldwideand haslimited treatment options. In view of this, zafirlukast (ZAF) was administered orally to DEN-induced HCC rats to evaluate its antineoplastic properties. ELISA, qRT-PCR and Western blot were used to determine the mole...
Source: Regulatory Toxicology and Pharmacology - October 10, 2019 Category: Toxicology Source Type: research
Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis.
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwideand haslimited treatment options. In view of this, zafirlukast (ZAF) was administered orally to DEN-induced HCC rats to evaluate its antineoplastic properties. ELISA, qRT-PCR and Western blot were used to determine the molecular mechanism associated with ZAF therapy for HCC. We found that HCC developed as a result of lower expression of caspases 3 and 9, but their levels returned to normal when the expression of eNOS, BAX, BAD, and Cyt C was decreased and when the expression of iNOS, Bcl-xl, and Bcl-2 was increased. Again, Z...
Source: Regulatory Toxicology and Pharmacology : RTP - October 8, 2019 Category: Toxicology Authors: Kumar P, Agarwal A, Singh AK, Gautam AK, Chakraborti S, Kumar U, Kumar D, Bhattacharya B, Panda P, Saha B, Qidwai T, Maity B, Saha S Tags: Regul Toxicol Pharmacol Source Type: research
Asthma pharmacotherapy: an update on leukotriene treatments.
Authors: Trinh HKT, Lee SH, Cao TBT, Park HS
Abstract
Introduction: Asthma is a chronic inflammatory disease of the airways with a large heterogeneity of clinical phenotypes. There has been increasing interest regarding the role of cysteinyl leukotriene (LT) and leukotriene receptor antagonists (LTRA) in asthma treatment. Areas covered: This review summarized the data (published in PubMed during 1984-2019) regarding LTRA treatment in asthma and LTs-related airway inflammation mechanisms. Involvement of LTs C4/D4/E4 has been demonstrated in the several aspects of airway inflammation and remodeling. Novel pa...
Source: Expert Review of Respiratory Medicine - September 24, 2019 Category: Respiratory Medicine Tags: Expert Rev Respir Med Source Type: research
CysLT1 receptor antagonists Pranlukast and Zafirlukast inhibit LRRC8-mediated volume regulated anion channels independently of the receptor.
This study provides clarifying insights into the putative role of leukotriene signaling in modulation of VRAC and identifies two new chemical scaffolds that can be used for development of more potent and specific VRAC inhibitors.
PMID: 31390227 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - August 6, 2019 Category: Cytology Authors: Figueroa EE, Kramer M, Strange K, Denton JS Tags: Am J Physiol Cell Physiol Source Type: research
Virtual screening of novel compounds as potential ER-alpha inhibitors.
Abstract
Majority of breast cancers diagnosed today are estrogen receptor (ER)-positive, however, progesterone receptor-positive (PR-positive) is also responsible for breast cancer. Tumors that are ER/PR-positive are much more likely to respond to hormone therapy than tumors that are ER/PR-negative. Nearly 105 ERa inhibitors from literature when docked resulted in 31 compounds (pyrazolo[1,5-a]pyrimidine analogs and chromen-2-one derivatives) with better binding affinities. The maximum score obtained was -175.282 kcal/mol for compound, [2-(4- Fluoro-phenylamino)-pyridin-3-yl]-{4-[2-phenyl-7- (3, 4, 5-trimet...
Source: Bioinformation - June 30, 2019 Category: Bioinformatics Authors: TilakVijay J, Vivek Babu K, Uma A Tags: Bioinformation Source Type: research
Capsule biopsy of acellular dermal matrix (ADM) to predict future capsular contracture in two-stage prosthetic breast reconstruction
Capsular contracture is a common reason for implant removal in implant-based breast surgery. Acellular dermal matrix (ADM) is often placed along the inferolateral border of the pectoralis major muscle in order to prevent capsular contracture.1 Leukotriene inhibitors, including Montelukast (Singulair) and Zafirlukast (Accolate), were recently introduced in research studies as medical agents to prevent capsular contracture. Systemic action of these medical agents, however, can bring unignorable side effects and cause additional economic burden. (Source: Journal of Plastic, Reconstructive and Aesthetic Surgery)
Source: Journal of Plastic, Reconstructive and Aesthetic Surgery - June 7, 2019 Category: Cosmetic Surgery Authors: Ara Kim, Jae Hoon Jung, Yoon-La Choi, Jai-Kyong Pyon Tags: Correspondence and Communications Source Type: research
