354 results match your criteria Drug Development Research[Journal]


Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain.

Drug Dev Res 2019 Feb 14. Epub 2019 Feb 14.

Department of Pharmacology, Faculty of Medicine, Pharmacology Program, ICBM, Universidad de Chile, Santiago, Chile.

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess as primary action mechanism the inhibition of cyclooxygenases (COX-1, COX-2, and COX-3), thus producing a decreasing prostaglandin synthesis. This study was designed to evaluate whether the antinociception induced by NSAIDs could be modulated by clomipramine or risperidone using a chemical model of inflammatory acute visceral pain, the abdominal acetic acid induced a writhing test in mice. Dose-response curves, intraperitoneal, or intrathecal for the antinociceptive activity displayed by ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol were analyzed in order to obtain the ED of each drug. Read More

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http://dx.doi.org/10.1002/ddr.21519DOI Listing
February 2019

Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2-induced PSMB5 in endothelial cells.

Drug Dev Res 2019 Feb 14. Epub 2019 Feb 14.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Atherosclerosis (AS) is one of important events involving in the pathological process of coronary artery disease. Many traditional Chinese medicines have been widely used for the treatment of AS. Previous studies have demonstrated that Ilexgenin A (IA) obtained from Ilex hainanensis Merr. Read More

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http://dx.doi.org/10.1002/ddr.21521DOI Listing
February 2019

Anti-neuroinflammatory effects of tannic acid against lipopolysaccharide-induced BV2 microglial cells via inhibition of NF-κB activation.

Drug Dev Res 2019 Feb 6. Epub 2019 Feb 6.

Department of Neurosurgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan, China.

Microglia mediated neuroinflammation is known to cause various neurodegenerative and neurological ailments. Tannic acid is a natural polyphenol which has been reported to possess antioxidant, anti-inflammatory, anticarcinogenic, antimutagenic, antitumor, and antimicrobial activities. As there are no reports till date on the anti-neuroinflammatory effects of tannic acid, this study was conducted to analyze the possible mechanism and pathway involved in the prevention of neuroinflammation by tannic acid in BV2 microglial cells. Read More

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http://dx.doi.org/10.1002/ddr.21490DOI Listing
February 2019
1 Read

Protective role of sitagliptin against oxidative stress in a kainic acid-induced status epilepticus in rats models via Nrf2/HO-1 pathway.

Drug Dev Res 2019 Feb 4. Epub 2019 Feb 4.

Biotech Center for Viral Disease Emergency, National Institute for Disease Control and Prevention, Chinese Disease Control and Prevention, Beijing, China.

Preclinical Research & Development Aim: Sitagliptin (Sita) is a dipeptidyl peptidase-4 inhibitor which has been approved as a curing medicine for Type 2 diabetes (T2D) and has also reported its neuroprotective and antioxidant activity. This article describes the therapeutic effects of Sita on induced rat model of SE by kainic acid (KA) and investigated the antioxidative pathway of sita.

Methods: Sprague-Dawley male rats were used randomly divided in four groups: vehicle control, KA and Sita + KA in a 5 and 10 mg/kg doses respectively in further groups. Read More

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http://dx.doi.org/10.1002/ddr.21516DOI Listing
February 2019

Can acetaminophen/dimethyl sulfoxide formulation prevent accidental and intentional acetaminophen hepatotoxicity?

Drug Dev Res 2019 Jan 30. Epub 2019 Jan 30.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.

An overdose of acetaminophen (APAP) causes liver injury in experimental animals and humans. The activation step (formation of reactive metabolite, N-acetyl-p-benzoquinone imine by cytochrome P450 system) and the consequent downstream pathway of oxidative stress, nitrosative stress, and inflammation play an important role in APAP-induced hepatotoxicity. Formulation of APAP with an inhibitor of the activation step would be ideal to prevent accidental and intentional APAP toxicity. Read More

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http://dx.doi.org/10.1002/ddr.21520DOI Listing
January 2019
2 Reads
0.734 Impact Factor

Mechanisms underlying isoliquiritigenin-induced apoptosis and cell cycle arrest via ROS-mediated MAPK/STAT3/NF-κB pathways in human hepatocellular carcinoma cells.

Drug Dev Res 2019 Jan 30. Epub 2019 Jan 30.

Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, China.

Hit, Lead & Candidate Discovery Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti-inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Read More

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http://doi.wiley.com/10.1002/ddr.21518
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http://dx.doi.org/10.1002/ddr.21518DOI Listing
January 2019
4 Reads
0.734 Impact Factor

Anticonvulsant evaluation and docking analysis of VV-Hemorphin-5 analogues.

Drug Dev Res 2019 Jan 25. Epub 2019 Jan 25.

Department of Behavioral Neurobiology, Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.

Preclinical Research & Development VV-Hemorphin-5 is an endogenous opioid peptide of the Hemorphin family with affinity at opioid receptors. A series of C-amide analogues have been synthesized, based on the structure of VV-Hemorphin-5, modified at position 1 and 7 by the un/natural amino acids (Aa8-Val-Val-Tyr-Pro-Trp-Thr-Gln-NH and Val-Val-Tyr-Pro-Trp-Thr-Aa1-NH ) using SPPS, Fmoc-chemistry. The peptide derivatives were evaluated for their anticonvulsant activity in three acute seizure tests in male ICR mice, the maximal electroshock (MES), the 6 Hz psychomotor seizure test, and the timed intravenous pentylenetetrazole (ivPTZ) infusion test. Read More

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http://dx.doi.org/10.1002/ddr.21514DOI Listing
January 2019

Structure-activity study of fluorine or chlorine-substituted cinnamic acid derivatives with tertiary amine side chain in acetylcholinesterase and butyrylcholinesterase inhibition.

Drug Dev Res 2019 Jan 24. Epub 2019 Jan 24.

College of Medicine, Hu'nan Normal University, Changsha, China.

Hit, Lead & Candidate Discovery In this study, a series of new fluorine or chlorine-substituted cinnamic acid derivatives that contain tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results show that almost all the derivatives containing tertiary amine side chain (compounds 4a-9d) exhibit moderate or potent activity in AChE inhibition. By contrast, their parent compounds (compounds 3a-3f) in the absence of tertiary amine moitery exhibit poor inhibitory activity against AChE. Read More

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http://dx.doi.org/10.1002/ddr.21515DOI Listing
January 2019

Curcumin reduces inflammation in knee osteoarthritis rats through blocking TLR4 /MyD88/NF-κB signal pathway.

Authors:
Yun Zhang Yu Zeng

Drug Dev Res 2019 Jan 21. Epub 2019 Jan 21.

Department of Hyperbaric Oxygen, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

Preclinical Research & Development Curcumin has been shown to possess a series of beneficial effects, such as antiinflammatory, antioxidant, analgesic, and promoting healing. However, the effect and relative mechanism of curcumin on knee osteoarthritis (OA) have not been elucidated. The aim of this study is to explore the protective effect of curcumin on monosodium iodoacetate (MIA)-induced OA. Read More

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http://doi.wiley.com/10.1002/ddr.21509
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http://dx.doi.org/10.1002/ddr.21509DOI Listing
January 2019
6 Reads

Inhibition of angiogenesis and tumor growth by a novel 1,4-naphthoquinone derivative.

Drug Dev Res 2019 Jan 11. Epub 2019 Jan 11.

Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.

Hit, Lead & Candidate Discovery Antiangiogenesis therapy is a promising way for treatment of solid cancers, and many angiogenesis inhibitors that target vascular endothelial growth factor (VEGF) or its receptors have been developed. We explored novel antiangiogenic compounds other than anti-VEGF drugs by screening our synthetic compound library and found that 6-thiophen-3-yl-2-methoxy-1,4-naphthoquinone (6-TMNQ) had potential as a novel angiogenesis inhibitor. This paper describes the effects of 6-TMNQ on angiogenesis and tumor growth in vitro and in vivo. Read More

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http://doi.wiley.com/10.1002/ddr.21513
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http://dx.doi.org/10.1002/ddr.21513DOI Listing
January 2019
8 Reads

Investigation of the antibacterial and antifungal activity of thiolated naphthoquinones.

Drug Dev Res 2019 Jan 4. Epub 2019 Jan 4.

Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Sciences, University of Pretoria, Onderstepoort, South Africa.

The WHO has stated that antibiotic resistance is escalating to perilously high levels globally and that traditional therapies of antimicrobial drugs are futile against infections caused by resistant microorganisms. Novel antimicrobial drugs are therefore required. We report in this study on the inhibitory activity of the 1,4-naphthoquinone-2,3-bis-sulfides and 1,4-naphthoquinone sulfides against two bacteria and a fungus to determine their antimicrobial properties. Read More

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http://doi.wiley.com/10.1002/ddr.21512
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http://dx.doi.org/10.1002/ddr.21512DOI Listing
January 2019
2 Reads

Protective effects of quercetin against inflammation and oxidative stress in a rabbit model of knee osteoarthritis.

Drug Dev Res 2019 Jan 4. Epub 2019 Jan 4.

Department of Orthopedics, The First People's Hospital of Yongkang, Jinhua, China.

Hit, Lead & Candidate Discovery This study investigated the effects of a natural phenolic compound quercetin on surgical-induced osteoarthritis (OA) in rabbits. Forty-eight New Zealand White rabbits were used to establish OA model by Hulth modified method, and subsequently randomized into untreated OA group (treatment was drinking water), celecoxib treated group (celecoxib 100 mg kg by gavage), and quercetin treated group (25 mg kg by gavage). Sixteen nonoperated rabbits served as the normal controls (drinking water was given). Read More

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http://doi.wiley.com/10.1002/ddr.21510
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http://dx.doi.org/10.1002/ddr.21510DOI Listing
January 2019
6 Reads

Graph theoretical analysis, in silico modeling, prediction of toxicity, metabolism and synthesis of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl) phenyl) quinazolin-4(3H)-ones as NMDA receptor inhibitor.

Drug Dev Res 2019 Jan 4. Epub 2019 Jan 4.

Department of Pharmacology, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.

Hit, Lead & Candidate Discovery A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d-aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. Read More

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http://doi.wiley.com/10.1002/ddr.21511
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http://dx.doi.org/10.1002/ddr.21511DOI Listing
January 2019
5 Reads

Alignment-based design and synthesis of new antimicrobial Aurein-derived peptides with improved activity against Gram-negative bacteria and evaluation of their toxicity on human cells.

Drug Dev Res 2019 Feb 28;80(1):162-170. Epub 2018 Dec 28.

Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.

Considering the worldwide increasing prevalence of resistance to traditional antibiotics, it is necessary to find new antibiotics to deal with this issue. Recently, antimicrobial peptides (AMPs) have been proposed as new antimicrobial agents. Aureins are a family of AMPs that are isolated from Green and Golden Bell Frogs. Read More

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http://dx.doi.org/10.1002/ddr.21503DOI Listing
February 2019
1 Read

Trichomonicidal activity of a new anthraquinone isolated from the roots of Morinda panamensis Seem.

Drug Dev Res 2019 Feb 20;80(1):155-161. Epub 2018 Dec 20.

Posgrado de Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico, D.F., Mexico.

Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common nonviral sexually transmitted infection worldwide. Although drug treatment is available, unpleasant side effects and increased resistance to the nitroimidazole family have been documented. Hence, there is a need for the identification of new and safe therapeutic agents against T. Read More

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http://doi.wiley.com/10.1002/ddr.21504
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http://dx.doi.org/10.1002/ddr.21504DOI Listing
February 2019
14 Reads

Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents.

Drug Dev Res 2019 Feb 20;80(1):179-186. Epub 2018 Dec 20.

Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.

In the quest for discovering potent antimicrobial agents with lower toxicity, we envisioned the design and synthesis of nalidixic acid-D-(+)-glucosamine conjugates. The novel compounds were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive bacteria, Gram negative bacteria and fungi. Cytotoxicity using MTT assay over L6 skeletal myoblast cell line, ATCC CRL-1458 was carried out. Read More

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http://doi.wiley.com/10.1002/ddr.21508
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http://dx.doi.org/10.1002/ddr.21508DOI Listing
February 2019
9 Reads

Synthesis, in vivo and in silico evaluation of novel 2,3-dihydroquinazolin-4(1H)-one derivatives as potential anticonvulsant agents.

Drug Dev Res 2018 Dec 19. Epub 2018 Dec 19.

Department of Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED ) values of 40. Read More

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http://dx.doi.org/10.1002/ddr.21506DOI Listing
December 2018
1 Read
0.734 Impact Factor

Biocatalytic synthesis of diaryl disulphides and their bio-evaluation as potent inhibitors of drug-resistant Staphylococcus aureus.

Drug Dev Res 2019 Feb 19;80(1):171-178. Epub 2018 Dec 19.

Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.

Staphylococcus aureus is a WHO Priority II pathogen for its capability to cause acute to chronic infections and to resist antibiotics, thus severely impacting healthcare systems worldwide. In this context, it is urgently desired to discover novel molecules to thwart the continuing emergence of antimicrobial resistance. Disulphide containing small molecules has gained prominence as antibacterials. Read More

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http://dx.doi.org/10.1002/ddr.21507DOI Listing
February 2019
1 Read

Tadalafil: 15 years' journey in male erectile dysfunction and beyond.

Authors:
Nermin S Ahmed

Drug Dev Res 2018 Dec 13. Epub 2018 Dec 13.

Faculty of Pharmacy and Biotechnology, Department of Pharmaceutical Chemistry, German University in Cairo, Cairo, Egypt.

Hit, Lead & Candidate Discovery Tadalafil, Cialis, Eli Lilly & Co./ICOS, (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6] pyrido[3,4-b]indole-1,4-dione, was first discovered in 2003. It was reported to have high diastereospecificity for phosphodiesterase 5 (PDE5) inhibitions. Read More

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http://dx.doi.org/10.1002/ddr.21493DOI Listing
December 2018
9 Reads

Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging.

Drug Dev Res 2019 Feb 11;80(1):98-105. Epub 2018 Dec 11.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.

Improving treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) is partly hampered by inadequate effective antitubercular agents. Development of bedaquiline and delamanid has potentially changed the treatment landscape for MDR-TB. This review provides an update on the progress of these novel antitubercular agents. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.21498
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http://dx.doi.org/10.1002/ddr.21498DOI Listing
February 2019
10 Reads
0.734 Impact Factor

Whole-genome sequencing for combatting antibiotic resistance.

Authors:
David Gurwitz

Drug Dev Res 2019 Feb 10;80(1):3-5. Epub 2018 Dec 10.

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.21496
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http://dx.doi.org/10.1002/ddr.21496DOI Listing
February 2019
11 Reads

Differential regulation of intestinal and hepatic CYP3A by 1α,25-dihydroxyvitamin D : Effects on in vivo oral absorption and disposition of buspirone in rats.

Drug Dev Res 2018 Dec 10. Epub 2018 Dec 10.

Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan, South Korea.

1α,25-Dihydroxyvitamin D (also called 1,25(OH) D or calcitriol) is the biologically active form of vitamin D, which functions as a ligand to the vitamin D receptor (VDR). It was previously reported that intestinal cytochrome P450 3A (CYP3A) expression was altered by 1,25(OH) D -mediated VDR activation. However, to clarify whether the change in CYP3A subfamily expression by VDR activation can affect metabolic function, further evidence is needed to prove the effect of 1,25(OH) D treatment on CYP3A-mediated drug metabolism and pharmacokinetics. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.21505
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http://dx.doi.org/10.1002/ddr.21505DOI Listing
December 2018
3 Reads

Evaluation of selected commercial pharmacotherapeutic drugs as potential pancreatic lipase inhibitors and antiproliferative compounds.

Drug Dev Res 2018 Dec 3. Epub 2018 Dec 3.

School of Pharmacy, University of Jordan, Amman, Jordan.

In this study, 15 commercial acidic drugs have been evaluated for pancreatic lipase (PL) inhibitory activity using an in vitro spectrophotometric method. The acidity was the basis of selection, since most PL inhibitors exhibit acidic groups and high lipophilicity. Orlistat was the robust reference agent for potency and efficacy determinations. Read More

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http://dx.doi.org/10.1002/ddr.21499DOI Listing
December 2018
4 Reads

Spontaneous mutations conferring antibiotic resistance to antitubercular drugs at a range of concentrations in Mycobacterium smegmatis.

Drug Dev Res 2019 Feb 3;80(1):147-154. Epub 2018 Dec 3.

Department of Biological Sciences, Benue State University, Makurdi, Benue State, Nigeria.

Mycobacteria populations can undergo mutations in their DNA sequence during replication, which if not repaired would be transferred to future generations. Earlier studies have tackled the estimation of mutation rate in mycobacteria at fixed concentrations. However, in this study, in vitro spontaneous mutations in Mycobacterium smegmatis (Msm) mc 155 (Msm) that confers resistance to some of the most important antitubercular drugs; isoniazid (INH ), rifampicin (RIF ), kanamycin (KAN ) and streptomycin (STR ) were first determined at several highly lethal concentrations, a few of which have not been previously investigated, in a fluctuation assay. Read More

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http://dx.doi.org/10.1002/ddr.21497DOI Listing
February 2019
1 Read

Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model.

Drug Dev Res 2018 Dec 3. Epub 2018 Dec 3.

Department of Gynaecology and Obstetrics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.

Primary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Read More

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http://dx.doi.org/10.1002/ddr.21500DOI Listing
December 2018
2 Reads
0.734 Impact Factor

Design and synthesis of simplified speciophylline analogues and β-carbolines as active molecules against Plasmodium falciparum.

Drug Dev Res 2019 Feb 29;80(1):133-137. Epub 2018 Nov 29.

Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, France.

A structure-activity relationship study of active molecules against chloroquine-resistant Plasmodium falciparum K1 strain is reported. Structurally simplified analogues of antiplasmodial active alkaloids presented similar levels of activity as their corresponding natural products extracted from Guiera senegalensis and Mitragyna inermis with IC values on chloroquine-resistant P. falciparum K1 strain of up to 10. Read More

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http://dx.doi.org/10.1002/ddr.21494DOI Listing
February 2019
2 Reads

Effect of Syringic acid on antioxidant biomarkers and associated inflammatory markers in mice model of asthma.

Drug Dev Res 2018 Nov 25. Epub 2018 Nov 25.

Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Preclinical Research & Development Asthma is termed as the induction of chronic inflammation in the airway lumen of lungs due to accumulation of inflammatory cells which affects normal breathing process. Prolonged accumulation of inflammatory cells leads to oxidative stress and suppression of antioxidant activities. Therefore, in our present investigation, a potential phenolic compound, Syringic acid was tested for the suppression of inflammatory markers toward an antiasthmatic activity in ovalbumin (OVA)-induced asthmatic mice model. Read More

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http://dx.doi.org/10.1002/ddr.21487DOI Listing
November 2018
2 Reads

Synthesis, anticonvulsant screening, and molecular modeling studies of new arylalkylimidazole oxime ether derivatives.

Drug Dev Res 2018 Nov 25. Epub 2018 Nov 25.

Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hacettepe University, Ankara, Turkey.

Hit, Lead & Candidate Discovery Preclinical Research & Development In this study, 15 new oxime ether derivatives were synthesized and their anticonvulsant activities were screened in vivo. The compounds were synthesized by the reaction of various alkyl halides with 1-(2-naphthyl)-2-(1H-imidazol-1-yl)ethanone oxime. Their anticonvulsant activities were determined using acute (maximal electroshock, subcutaneous metrazol [SCM], and 6 Hz seizure test) and chronic (corneal-kindled mouse) seizure models, their neurotoxic effects were evaluated by models of behavioral toxicity according to the Epilepsy Therapy Screening Program protocol of the NIH. Read More

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http://dx.doi.org/10.1002/ddr.21491DOI Listing
November 2018
11 Reads

Microsponge: An emerging drug delivery strategy.

Drug Dev Res 2018 Nov 19. Epub 2018 Nov 19.

Department of Pharmacology, School of pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan, India.

Hit, Lead & Candidate Discovery Microsponges are the spherical particles ranging from 5 to 300 μm in size. These are further made up of clusters of smaller spheres. They are designed for delivering the drug efficiently at a comparatively lesser dose and enhancing the stability, modifying the drug release profile and minimizing the side effects. Read More

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http://dx.doi.org/10.1002/ddr.21492DOI Listing
November 2018
1 Read

Drug sales confirm clinical advantage of multi-target inhibition of drug escapes by anticancer kinase inhibitors.

Drug Dev Res 2018 Nov 13. Epub 2018 Nov 13.

Bioinformatics and Drug Design Group, Department of Pharmacy, National University of Singapore, Singapore, Singapore.

Hit, Lead & Candidate Discovery The clinical advantage of co-targeting cancer drug escape has been indicated by the percentage of these co-targeting drugs among all multi-target drugs in clinics and clinical trials. This clinical advantage needs to be further interrogated from such perspectives as the clinical impact of multi-target inhibition of drug-escape mediators. This impact may be reflected by drug sales data, that is, multi-target inhibition of higher number of drug-escape mediators favors the expanded coverage of drug-resistant patients leading to higher sales. Read More

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http://doi.wiley.com/10.1002/ddr.21486
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http://dx.doi.org/10.1002/ddr.21486DOI Listing
November 2018
14 Reads

Preparation, optimization, and pharmacokinetic study of nanoliposomes loaded with triacylglycerol-bound punicic acid for increased antihepatotoxic activity.

Drug Dev Res 2018 Nov 10. Epub 2018 Nov 10.

Department of Pharmaceutics and Tissue Engineering, School of Pharmacy, Jiangsu University, Zhenjiang, P.R. China.

Hit, Lead & Candidate Discovery Punicic acid of pomegranate oil (PAP) has gained heightened interest due to several health benefits, such as anticarcinogenic, antidiabetic, and antiatherosclerotic properties. However, these bioactivities have been hampered by chemical instability, poor water solubility, rapid metabolism, and low bioavailability of PAP. Therefore, this study was aimed at optimizing the liposomal formulation of Triacylglycerol-bound punicic acid with its regioisomers (TPAR) for improved oral bioavailability and increased hepatoprotection through antioxidation and anti-inflammation. Read More

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http://doi.wiley.com/10.1002/ddr.21485
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http://dx.doi.org/10.1002/ddr.21485DOI Listing
November 2018
11 Reads
0.734 Impact Factor

Functional mechanism of tracheal relaxation, antiasthmatic, and toxicological studies of 6-hydroxyflavone.

Drug Dev Res 2018 Nov 5. Epub 2018 Nov 5.

Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico.

Preclinical Research & Development Previously, we described tracheal rat rings relaxation by several flavonoids, being 6-hydroxyflavone (6-HOF) the most active derivative of the series. Thus, its mechanism of action was determined in an ex vivo tracheal rat ring bioassay. The anti-asthmatic effect was assayed in in vivo OVAlbumin (OVA)-sensitized guinea pigs. Read More

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http://doi.wiley.com/10.1002/ddr.21484
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http://dx.doi.org/10.1002/ddr.21484DOI Listing
November 2018
17 Reads
0.734 Impact Factor

Silver carbene complexes: An emerging class of anticancer agents.

Drug Dev Res 2018 Nov 1. Epub 2018 Nov 1.

University of Kansas Medical Center, Kansas City, Kansas.

Hit, Lead & Candidate Discovery Cancer is a major global health problem with large therapeutic challenges. Although substantial progress has been made in cancer therapy, there still remains a need to develop novel and effective treatment strategies to treat several relapsed and refractory cancers. Recently, there has been growing demand for considering organometallics as antineoplastic agents. Read More

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http://doi.wiley.com/10.1002/ddr.21478
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http://dx.doi.org/10.1002/ddr.21478DOI Listing
November 2018
3 Reads

Design, synthesis, and biological evaluation of Helicobacter pylori inosine 5'-monophosphate dehydrogenase (HpIMPDH) inhibitors.

Drug Dev Res 2019 Feb 1;80(1):125-132. Epub 2018 Nov 1.

Department of Pharmaceutical Chemistry, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, India.

Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes a crucial step in the biosynthesis of guanine nucleotides. Being a validated target for immunosuppressive, antiviral, and anticancer drug development, lately it has been exploited as a promising target for antimicrobial therapy. Extending our previous work on Mycobacterium tuberculosis IMPDH, GuaB2, inhibitor development, we screened a set of 23 new chemical entities (NCEs) with substituted flavone (Series 1) and 1,2,3-triazole (Series 2) core structures for their in vitro Helicobacter pylori IMPDH (HpIMPDH) and human IMPDH2 (hIMPDH2) inhibitory activities. Read More

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http://dx.doi.org/10.1002/ddr.21467DOI Listing
February 2019
9 Reads

Protective role of fucoxanthin in diethylnitrosamine-induced hepatocarcinogenesis in experimental adult rats.

Drug Dev Res 2018 Oct 31. Epub 2018 Oct 31.

The Laboratory Animal Center of Chongqing Medical University, Chongqing, China.

Hit, Lead & Candidate Discovery Hepatocellular carcinoma (HCC) accounts for majority of cancer related deaths. Two major risk factors in induction of HCC are chemical and virus, however, the possible mechanisms of their differences remain indefinable. The current study focused on protective role of Fucoxanthin (Fx) in liver affected by diethylnitrosamine (DEN)-induced HCC. Read More

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http://doi.wiley.com/10.1002/ddr.21451
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http://dx.doi.org/10.1002/ddr.21451DOI Listing
October 2018
7 Reads

Selective cytotoxic activity and DNA damage by an epoxyalkyl galactopyranoside.

Drug Dev Res 2018 Dec 30;79(8):426-436. Epub 2018 Oct 30.

Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain.

Preclinical Research & Development Several clinically useful anticancer drugs selectively kill cancer cells by inducing DNA damage; the genomic instability and DNA repair defects of cancer cells make them more vulnerable than normal cells to the cytotoxicity of DNA-damaging agents. Because epoxide-containing compounds can induce DNA damage, we have used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the selective cytotoxicity of three epoxyalkyl galactopyranosides against A549 lung cancer cells and MRC-5 lung normal cells. Compound (2S,3S)-2,3-epoxydecyl 4,6-O-(S)-benzylidene-β-d-galactopyranoside (EDBGP) showed the highest selective anticancer activity and was selected for mechanistic studies. Read More

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http://doi.wiley.com/10.1002/ddr.21483
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http://dx.doi.org/10.1002/ddr.21483DOI Listing
December 2018
15 Reads

Antibiotics as both friends and foes of the human gut microbiome: The microbial community approach.

Drug Dev Res 2019 Feb 28;80(1):86-97. Epub 2018 Oct 28.

Institut de Systématique, Evolution, Biodiversité (ISYEB), Sorbonne Université, Muséum National d'Histoire naturelle, CNRS, EPHE, CP, Paris, France.

The exposure of the human gut to antibiotics can have a great impact on human health. Antibiotics pertain to the preservation of human health and are useful tools for fighting bacterial infections. They can be used for curing infections and can play a critical role in immunocompromised or chronic patients, or in fighting childhood severe malnutrition. Read More

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http://doi.wiley.com/10.1002/ddr.21466
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http://dx.doi.org/10.1002/ddr.21466DOI Listing
February 2019
13 Reads

Marine bacteria and fungi as promising source for new antibiotics.

Drug Dev Res 2019 Feb 28;80(1):24-27. Epub 2018 Oct 28.

RD3 - Marine Ecology, RU - Marine Microbiology, GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany.

Natural products and derivatives thereof are of considerable importance in the discovery of new pharmaceuticals, for example, for the treatment of cancer, diabetes, inflammation diseases, and infection diseases caused by bacteria, fungi, viruses, or parasites. The great biodiversity of marine microorganisms is reflected in their huge chemical diversity, which provides a rich source of biologically active compounds. An increasing interest in marine microorganisms as promising producers of new compounds with potential medical applications has raised increasing interest in the sustainable exploration of marine microbial resources for the discovery of new antibiotics, which is highlighted. Read More

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http://doi.wiley.com/10.1002/ddr.21482
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http://dx.doi.org/10.1002/ddr.21482DOI Listing
February 2019
4 Reads

Participation of ATP-sensitive K+ channels and μ-opioid receptors in the antinociceptive synergism of the paracetamol-tapentadol co-administration in the formalin-induced pain assay in mice.

Drug Dev Res 2018 Dec 26;79(8):400-405. Epub 2018 Oct 26.

Departamento de Clínicas, División de Ciencias Biomédicas, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán, Jalisco, Mexico.

Preclinical Research & Development The purpose of this study was to assess the interaction and mechanisms of action of the paracetamol-tapentadol combination in the formalin-induced pain model in mice. Paracetamol (56.23-562. Read More

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http://dx.doi.org/10.1002/ddr.21476DOI Listing
December 2018
4 Reads
0.734 Impact Factor

A brief appraisal of computational modeling of antimicrobial peptides' activity.

Authors:
Jagannath Mondal

Drug Dev Res 2019 Feb 21;80(1):28-32. Epub 2018 Oct 21.

Tata Institute of Fundamental Research, Center for Interdisciplinary Sciences, Hyderabad 500107, India.

We present a brief overview of computer simulations over the span of last two decades that have made some serious attempts in providing key insights toward the mechanistic aspects of antimicrobial peptides and biomimetic peptides. We review some of the success stories of computational modeling of antimicrobial activity and also point toward the present shortcomings of the current approaches. Finally, we shed light upon the future potential directions that computational approach can adopt toward direct and closer comparisons with experiments on antimicrobial activity. Read More

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http://dx.doi.org/10.1002/ddr.21472DOI Listing
February 2019
1 Read

Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors.

Drug Dev Res 2018 Dec 21;79(8):406-425. Epub 2018 Oct 21.

Department of Pharmaceutical Chemistry, Istanbul Medipol University, School of Pharmacy, Istanbul, Turkey.

Hit, Lead & Candidate Discovery After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid-20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.21481
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http://dx.doi.org/10.1002/ddr.21481DOI Listing
December 2018
8 Reads

Dose translation between laboratory animals and human in preclinical and clinical phases of drug development.

Drug Dev Res 2018 Oct 21. Epub 2018 Oct 21.

Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, UAE.

Preclinical Research & Development Appropriate translation and determination of the maximum recommended starting dose in human is a vital task in new drug development and research. Allometric scaling is the most frequently used approach for dose extrapolation based on normalization of dose-to-body surface area. Misinterpretation of allometric dose conversion and safety factor application can lead to major problems in calculating maximum recommended safe starting dose in first-in-human clinical trials. Read More

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http://doi.wiley.com/10.1002/ddr.21461
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http://dx.doi.org/10.1002/ddr.21461DOI Listing
October 2018
8 Reads
0.734 Impact Factor

Inhibiting conjugation as a tool in the fight against antibiotic resistance.

Drug Dev Res 2019 Feb 21;80(1):19-23. Epub 2018 Oct 21.

Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.

Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches to the problem of antibiotic resistance are sorely needed and this commentary highlights one relatively unexplored target for drug development: conjugation. Conjugation is a common mechanism of horizontal gene transfer in bacteria that is instrumental in the spread of antibiotic resistance among bacteria. Read More

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http://dx.doi.org/10.1002/ddr.21457DOI Listing
February 2019
7 Reads

Drug development and bioanalytical method validation for a novel anticancer molecule, 4-(dimethylamino)-2-(p-tolylamino) thiazole-5-carbonitrile.

Drug Dev Res 2018 Dec 17;79(8):391-399. Epub 2018 Oct 17.

National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat, India.

Hit, Lead & Candidate Discovery The thiazole ring system represents a significant building block that exists in many biologically active natural products and clinically successful anticancer drugs. Modifications of the thiazole core have been a proven and highly effective method in improving anticancer potency. We designed a novel thiazole-based molecule, 4-(dimethylamino)-2-(p-tolylamino) thiazole-5-carbonitrile, which showed potent in vitro anticancer effect against targeted Bcl-2 Jurkat cell-line quantified using 3-(4, 5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Read More

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http://doi.wiley.com/10.1002/ddr.21462
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http://dx.doi.org/10.1002/ddr.21462DOI Listing
December 2018
16 Reads

Reaching toward underexplored targets in antibacterial drug design.

Drug Dev Res 2019 Feb 12;80(1):6-10. Epub 2018 Oct 12.

Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.

The increase of antimicrobial resistance necessitates the renewal and strong research involvement in antibacterial drug design. In the following work, we comment on the key approaches used in development of new antibacterials, focusing on intracellular therapeutic targets that have been so far mostly underexplored: the enzymes of the Mur pathway MurA to MurF. We identify common obstacles observed during research on MurA, MurB, and Mur ligases inhibitors and their development into potential antibacterial compounds, and discern several approaches and solutions to tackle the whole-cell activity of designed compounds. Read More

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http://doi.wiley.com/10.1002/ddr.21465
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http://dx.doi.org/10.1002/ddr.21465DOI Listing
February 2019
2 Reads

Drug resistance in Mycobacterium tuberculosis and targeting the l,d-transpeptidase enzyme.

Drug Dev Res 2019 Feb 12;80(1):11-18. Epub 2018 Oct 12.

The Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Tuberculosis (TB) is a disease that has afflicted mankind for thousands of years, but in the last seven decades, much progress has been made in anti-TB therapy. Early drugs, such as para-aminosalicylic acid, streptomycin, isoniazid, and rifamycins were very effective in combatting the disease, giving rise to the hope that TB would be eradicated from the face of the earth by 2010. Despite that optimism, TB continues to kill more than a million people annually worldwide. Read More

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http://doi.wiley.com/10.1002/ddr.21455
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http://dx.doi.org/10.1002/ddr.21455DOI Listing
February 2019
19 Reads

Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance.

Drug Dev Res 2019 Feb 10;80(1):33-47. Epub 2018 Oct 10.

Department of Chemistry and Biochemistry, Butler University, Indianapolis, Indiana.

The rise of antibiotic resistance necessitates the search for new platforms for drug development. Prodrugs are common tools for overcoming drawbacks typically associated with drug formulation and delivery, with ester prodrugs providing a classic strategy for masking polar alcohol and carboxylic acid functionalities and improving cell permeability. Ester prodrugs are normally designed to have simple ester groups, as they are expected to be cleaved and reactivated by a wide spectrum of cellular esterases. Read More

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http://doi.wiley.com/10.1002/ddr.21468
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http://dx.doi.org/10.1002/ddr.21468DOI Listing
February 2019
13 Reads

Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3-oxazine derivatives.

Drug Dev Res 2018 Nov 10;79(7):352-361. Epub 2018 Oct 10.

School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa.

Hit, Lead & Candidate Discovery A series of 1-(6-methyl-2-substituted phenyl-4-thioxo-4H-1,3-oxazin-5-yl)ethanones (3a-n) were synthesized by the reaction of benzoyl isothiocyanates with active methylene compound acetylacetone in the presence of triethyl amine in a one-pot process. The structures of the products were elucidated by elemental analyses, FT-IR, H NMR, C NMR, and mass spectroscopy. These new 1,3-oxazine derivatives were evaluated for their inhibitory activity against carbonic anhydrase II. Read More

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http://dx.doi.org/10.1002/ddr.21464DOI Listing
November 2018
1 Read

Actinomycin-D and dimethylamino-parthenolide synergism in treating human pancreatic cancer cells.

Drug Dev Res 2018 09 17;79(6):287-294. Epub 2018 Sep 17.

University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Preclinical Research & Development Pancreatic cancer is the third leading cause of death in the US with a poor 5-year survival rate of 8.5%. A novel anti-cancer drug, dimethylamino parthenolide (DMAPT), is the water-soluble analog of the natural sesquiterpene lactone, parthenolide. Read More

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http://doi.wiley.com/10.1002/ddr.21441
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http://dx.doi.org/10.1002/ddr.21441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193836PMC
September 2018
2 Reads

In-house chemical library repurposing: A case example for Pseudomonas aeruginosa antibiofilm activity and quorum sensing inhibition.

Drug Dev Res 2018 Dec 6;79(8):383-390. Epub 2018 Oct 6.

Microbiology Division, CSIR-Central Drug Research Institute, Lucknow, India.

Hit, Lead & Candidate Discovery Drug repurposing has become a recent trend in drug development programs, where previously developed drugs are explored for hit and redeveloped into potential therapeutic agents for new diseases. Globally, in any drug development program, a series of molecules are synthesized and evaluated for the hypothesized activity. Hits are developed into lead molecules or drugs, whereas the negative ones are shelved in the lab with no immediate use. Read More

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http://dx.doi.org/10.1002/ddr.21458DOI Listing
December 2018
2 Reads
0.734 Impact Factor