scholarly journals Antimicrobial Activity of Quinazolin Derivatives of 1,2-Di(quinazolin-4-yl)diselane against Mycobacteria

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Bikui Tang ◽  
Meili Wei ◽  
Qun Niu ◽  
Yinjiu Huang ◽  
Shuo Ru ◽  
...  
Keyword(s):  
New Drugs ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Quinazoline Derivative ◽  
Damage Level ◽  
New Strategy ◽  
Quinazoline Derivatives ◽  
Clinical Drugs ◽  
Dose Dependent ◽  
Derivatives Of

Mycobacterium tuberculosis (M. tuberculosis) is one of the leading causes of morbidity and mortality. Currently, the emergence of drug resistance has an urgent need for new drugs. In previous study, we found that 1,2-di(quinazolin-4-yl)diselane (DQYD), a quinazoline derivative, has anticancer activities against many cancers. However, whether DQYD has the activity of antimycobacterium is still little known. Here our results show that DQYD has a similar value of the minimum inhibitory concentration with clinical drugs against mycobacteria and also has the ability of bacteriostatic activity with dose-dependent and time-dependent manner. Furthermore, the activities of DQYD against M. tuberculosis are associated with intracellular ATP homeostasis. Meanwhile, mycobacterium DNA damage level was increased after DQYD treatment. But there was no correlation between survival of mycobacteria in the presence of DQYD and intercellular reactive oxygen species. This study enlightens the possible benefits of quinazoline derivatives as potential antimycobacterium compounds and furtherly suggests a new strategy to develop new methods for searching antituberculosis drugs.

scholarly journals Biofabricated Fatty Acids-Capped Silver Nanoparticles as Potential Antibacterial, Antifungal, Antibiofilm and Anticancer Agents

2021 ◽  
Vol 14 (2) ◽  
pp. 139
Author(s):  
Mohammad Azam Ansari ◽  
Sarah Mousa Maadi Asiri ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
Ahmad Almatroudi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Silver Nanoparticles ◽  
Anticancer Agents ◽  
Sem Analysis ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Anticancer Efficacy ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Dose Dependent

The current study demonstrates the synthesis of fatty acids (FAs) capped silver nanoparticles (AgNPs) using aqueous poly-herbal drug Liv52 extract (PLE) as a reducing, dispersing and stabilizing agent. The NPs were characterized by various techniques and used to investigate their potent antibacterial, antibiofilm, antifungal and anticancer activities. GC-MS analysis of PLE shows a total of 37 peaks for a variety of bio-actives compounds. Amongst them, n-hexadecanoic acid (21.95%), linoleic acid (20.45%), oleic acid (18.01%) and stearic acid (13.99%) were found predominately and most likely acted as reducing, stabilizing and encapsulation FAs in LIV-AgNPs formation. FTIR analysis of LIV-AgNPs shows some other functional bio-actives like proteins, sugars and alkenes in the soft PLE corona. The zone of inhibition was 10.0 ± 2.2–18.5 ± 1.0 mm, 10.5 ± 2.5–22.5 ± 1.5 mm and 13.7 ± 1.0–16.5 ± 1.2 against P. aeruginosa, S. aureus and C. albicans, respectively. LIV-AgNPs inhibit biofilm formation in a dose-dependent manner i.e., 54.4 ± 3.1%—10.12 ± 2.3% (S. aureus), 72.7 ± 2.2%–23.3 ± 5.2% (P. aeruginosa) and 85.4 ± 3.3%–25.6 ± 2.2% (C. albicans), and SEM analysis of treated planktonic cells and their biofilm biomass validated the fitness of LIV-AgNPs in future nanoantibiotics. In addition, as prepared FAs rich PLE capped AgNPs have also exhibited significant (p < 0.05 *) antiproliferative activity against cultured HCT-116 cells. Overall, this is a very first demonstration on employment of FAs rich PLE for the synthesis of highly dispersible, stable and uniform sized AgNPs and their antibacterial, antifungal, antibiofilm and anticancer efficacy.

scholarly journals Synthesis and evaluation of some novel derivatives of 2-propoxybenzylidene isonicotinohydrazide for their potential antimicrobial activity

2012 ◽  
Vol 77 (5) ◽  
pp. 589-597 ◽  
Author(s):  
Manav Malhotra ◽  
Manu Arora ◽  
Abdul Samad ◽  
Kapendra Sahu ◽  
Priyanka Phogat ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Mannich Bases ◽  
Dependent Manner ◽  
Lung Adenocarcinoma Cell Line ◽  
Ic50 Values ◽  
Nmr Methods ◽  
Human Lung Adenocarcinoma Cell ◽  
Dose Dependent ◽  
Derivatives Of

A novel series of Mannich which contained isoniaside were prepared. First by the reaction of 2-propoxybenzaldehyde with isoniazid corresponding hydrazone (2a) was obtained. After that, product 2a after mannich reaction of aminomethylation with formaldehyde and secondary give amines (2b-2k). The inhibitory potencies of the synthesized compounds were assayed in vitro against a panel of microorganisms and against A549 human lung adenocarcinoma cell line. Compounds 2c and 2k displayed moderate to potent antimicrobial activity against all the tested strains and they also exhibited significant cytotoxicity in a dose-dependent manner with an IC50 values ranging from 2.84 to 8.55 (?g) and 0.007-0.030 (?M). The structures of newly synthesized compounds were evaluated by elemental and spectral (IR, 1HNMR, 13C-NMR) methods. The result demonstrates the potential and importance of developing new mannich bases which would be effective against resistant microbial strain and they may be useful leads for anticancer drug development in the future.

scholarly journals Transcriptomic Profile of Mycobacterium smegmatis in Response to an Imidazo[1,2-b][1,2,4,5]tetrazine Reveals Its Possible Impact on Iron Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Aleksey A. Vatlin ◽  
Egor A. Shitikov ◽  
Mohd Shahbaaz ◽  
Dmitry A. Bespiatykh ◽  
Ksenia M. Klimina ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mechanism Of Action ◽  
Iron Metabolism ◽  
Mycobacterium Smegmatis ◽  
New Drugs ◽  
Dependent Manner ◽  
Tuberculosis Control ◽  
Transcriptomic Response ◽  
Dose Dependent ◽  
Siderophore Synthesis

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex bacteria, is one of the most pressing health problems. The development of new drugs and new therapeutic regimens effective against the pathogen is one of the greatest challenges in the way of tuberculosis control. Imidazo[1,2-b][1,2,4,5]tetrazines have shown promising activity against M. tuberculosis and M. smegmatis strains. Mutations in MSMEG_1380 lead to mmpS5–mmpL5 operon overexpression, which provides M. smegmatis with efflux-mediated resistance to imidazo[1,2-b][1,2,4,5]tetrazines, but the exact mechanism of action of these compounds remains unknown. To assess the mode of action of imidazo[1,2-b][1,2,4,5]tetrazines, we analyzed the transcriptomic response of M. smegmatis to three different concentrations of 3a compound: 1/8×, 1/4×, and 1/2× MIC. Six groups of genes responsible for siderophore synthesis and transport were upregulated in a dose-dependent manner, while virtual docking revealed proteins involved in siderophore synthesis as possible targets for 3a. Thus, we suggest that imidazo[1,2-b][1,2,4,5]tetrazines may affect mycobacterial iron metabolism.

scholarly journals Zingiber Officinale Roscoe and Echinops Kebericho Mesfin Showed Antiplasmodial Activities against Plasmodium Berghei in a Dosedependent Manner in Ethiopia

1970 ◽  
Vol 28 (5) ◽  
Author(s):  
Abdissa Biruksew ◽  
Ahmed Zeynudin ◽  
Yonas Alemu ◽  
Lemu Golassa ◽  
Moti Yohannes ◽  
...  
Keyword(s):  
Body Weight ◽  
Statistical Significance ◽  
Herbal Medicines ◽  
Negative Control ◽  
New Drugs ◽  
Dependent Manner ◽  
Survival Times ◽  
Plant Materials ◽  
Dose Dependent

BACKGROUND: The emergence and spread of Plasmodium falciparum resistance to antimalarial drugs necessitated the search for new drugs from natural products. Zingiber officinal Roscoe and Echinops Kebericho Mesfin are traditional herbal medicines widely used for the treatment of malaria in Ethiopia. The aim of the study was to assess the toxicity profile and in vivo antiplasmodial activities of 70% methanol crude extracts of both plant materials against Plasmodium berghei.METHODS: Healthy male Swiss Albino mice of age 4-5 weeks and weight 25-36 g were infected by P. berghei. The extracts were administered orally at doses 5000, 2500 and 1250 mg/kg for acute toxicity of E. kebericho Mesfin. Graded doses at 1000, 500 and 250 mg/kg used for four days suppressive studies. Parasitemia, body weight, packed cell volume (PCV) and survival time were determined. SPSS Version 20 was used for the analysis of data of parasitemia, body weight, PCV, and survival times. Statistical significance was determined by one-way ANOVA. Independent ttest was used to compare results. Results were presented as a mean ± standard error of the mean (M ± SEM). All data were analyzed at a 95% confidence interval (α= 0.05).RESULTS: At the dose of 5000 mg/kg, E. kebericho Mesfin showed no toxic effects. The LD50 of extract could go beyond the dose used. In vivo antiplasmodial activity of extracts showed excellent chemo suppression at 500 and 1000 mg/kg in a dose dependent manner compared with the negative control. The chemo suppressions of the 1000 mg/kg of both plant extracts were 49.53 ± 1.90% and 32.83 ± 1.03%, respectively. The survival times of P. berghei infected mice were also a dose dependent manner while failed to prevent weight loss.CONCLUSION: The extracts of both medicinal plants showed antiplasmodial activities against P. berghei. It confirmed the literature findings and their traditional uses. 

In Vitro Antisickling Effects of Novel Pyridyl Derivatives with Enhanced Potency.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2347-2347
Author(s):  
Osheiza Y. Abdulmalik ◽  
Martin K. Safo ◽  
Gajanan Joshi ◽  
Jisheng Yang ◽  
Qiukan Chen ◽  
...  
Keyword(s):  
Schiff Base ◽  
Plasma Concentration ◽  
In Vitro Studies ◽  
Dependent Manner ◽  
High Affinity ◽  
Concentration Time ◽  
Hb S ◽  
Dose Dependent ◽  
Derivatives Of

Abstract Chemical modification of sickle hemoglobin (Hb S) to form stable high affinity Schiff-base adducts has been an attractive approach towards finding a potential therapeutic option for sickle cell disease (SCD). An ideal candidate drug should rapidly enter the bloodstream, permeate red blood cell membrane, bind specifically with intracellular Hb S and inhibit cell sickling with minimal adverse effect. In an effort to find drugs that satisfy these criteria, we recently designed, synthesized and studied three novel benzaldehydes (INN-296, INN-298 and INN-312) with enhanced potency. The compounds are pyridyl derivatives of benzaldehyde, and hence, combine structural features of two previously determined antisickling agents: vanillin and pyridoxal. All three compounds shifted the allosteric equilibrium of Hb S toward the oxy- or R-state by destabilizing the deoxy- or T-state. The results of in vitro studies of the antisickling effects of a representative compound (INN-312) are reported. Upon incubation of suspensions of sickle erythrocytes (SS cells) with 0.5, 1 or 2 mM of INN-312 under hypoxia (4% O2 :96% N2) at 37°C, sickling of SS cells was inhibited in a dose-dependent manner (15 ± 2, 44 ± 10 and 81 ± 8% inhibition, respectively). Cation-exchange HPLC analysis of lysates from the pre-incubated SS cells revealed a new peak in addition to the original Hb S peak, indicative of formation of Schiff-base adducts of Hb. Oxygen equilibrium curves (OECs) of SS-cell suspensions and lysates were shifted toward the left in a dose-dependent manner. X-ray crystal structures of these derivatives revealed their symmetric binding to the two N-terminal αVal1 of Hb S, and seem to indicate that their superior antisickling activity may arise from effector-induced interference with Hb S polymerization, as well as shifting the OEC to the high affinity state. In vitro studies on INN-296 and INN-298 showed similar results. Studies in vivo were performed using transgenic sickle mice (3 mice per group). The mice were treated intraperitoneally with single doses of 50, 100 or 150 mg/kg of INN-312. To study pharmacokinetic profiles of INN-312 in treated mice, blood samples (~20 μl each) were collected under anesthesia via retro-orbital venipuncture into EDTA tubes at 30 min, 1 h and every hour afterwards for 5 hours. Plasma from each sample was de-proteinized and analyzed by reversed-phase HPLC for quantification of INN-312 present in the blood. A non-compartmental pharmacokinetic model with first-order elimination rate was used to determine the plasma concentration-time data using PK Solutions 2.0 software (SUMMIT Research Services, Montrose, CO, USA). The area under the plasma concentration curve (AUC) increased in a dose-dependent manner (314 ± 22 μg/ml/min, 648 ± 33 μg/ml/min and 1044 ± 63 μg/ml/min in mice treated with 50, 100 and 150 mg/kg, respectively). The terminal half-life (T1/2= 0.75 ± 0.15 h), peak concentration time (Tmax= 0.5 h), and mean resident time (MRT= 1.2 ± 0.2 h) values were consistent for all three dosage groups. The observed maximum plasma concentration (Cmax)was also increased in a dose-dependent manner. These novel pyridyl derivatives of benzaldehyde shifted the position of Hb OEC toward the left most strongly among various compounds reported to date. Further detailed studies are necessary to validate this approach to developing better antisickling agents.

scholarly journals THE MOLLUSC IONIC CURRENTS CHANGES AFTER ADMINISTRATION OF N-PHENYLALKYL DERIVATIVES OF TAURINE

2012 ◽  
Vol 10 (4) ◽  
pp. 67-72
Author(s):  
Anatoliy Ivanovich Vislobokov ◽  
Lyudmila Konstantinovna Khnychenko ◽  
Yuriy Dmitriyevich Ignatov ◽  
Nikolay Sergeyevich Sapronov ◽  
Petr Dmitriyevich Shabanov
Keyword(s):  
Lymnaea Stagnalis ◽  
Ionic Currents ◽  
Ionic Channels ◽  
Dependent Manner ◽  
Isolated Neurons ◽  
Sodium Potassium ◽  
Fixed Membrane ◽  
Kinetics Of ◽  
Dose Dependent ◽  
Derivatives Of

The transmembrane sodium, potassium and calcium ionic currents were studied after extracellular administration of N-phenylalkyl derivatives of taurine in concentrations 1, 10, 100 and 1000 mM. The method of intracellular dialysis with fixed membrane potential was used in model of isolated neurons of the mollusks Lymnaea stagnalis and Planorbarius corneus. The solutions containing 1 and 10 mM of the compounds studied did not change ionic channels activity in isolated neurons. Concentrations 100 and mM depressed reversibly all currents in the dose-dependent manner: taurine < TAU-02 < TAY-15 < TAU-60. The voltage-amplitude membrane characteristics as well as kinetics of the currents did not change.

scholarly journals Effect of multiple emulsion on mortality of drosophila virils

2019 ◽  
Vol 10 (3) ◽  
pp. 2446-2451
Author(s):  
Areej Al-Khalaf
Keyword(s):  
Peritrophic Membrane ◽  
Dependent Manner ◽  
Multiple Emulsion ◽  
Frequent Use ◽  
New Strategy ◽  
Insect Populations ◽  
Hind Gut ◽  
Pass Through ◽  
Number Of Individuals ◽  
Dose Dependent

The frequent use of insecticides has led to the development of insecticide resistance by many insects. In some insect populations, resistance can be developed to multiple pesticides. Up to this, insecticides resistance became a key challenge, and the amounts of the used pesticides must be as lower as possible. In this study, we measured the potency of multiple emulsions on the mortality of Drosophila virils and the ability of the fly to ingest and excrete the emulsions as a new strategy to avoid the great use of pesticides.  The obtained data showed that the value of the lethal concentration of half the number of individuals decreases when the exposure duration increases, which demonstrates the sensitivity of the larvae to the toxic effect of the formulation. This can help to suggest that this type of material can be more effective and lasting effect for as long as possible. Moreover, the ingestion and excretion of the formulated product in the hind-gut can help to suggest the ability of the studied formulation to pass through the peritrophic membrane and the midgut acidic regions as two important barriers. In conclusion, the formulated microcapsule has a satisfactory insecticidal potency against D. virilis in a dose-dependent manner which might help to avoid the developed resistance to commonly used insecticides.

ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 613-620 ◽  
Author(s):  
Max Schnurr ◽  
Tracey Toy ◽  
Patrizia Stoitzner ◽  
Paul Cameron ◽  
Amanda Shin ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cell Types ◽  
Calcium Flux ◽  
Dependent Manner ◽  
Vaccination Site ◽  
Migratory Capacity ◽  
New Strategy ◽  
Antigen Presenting ◽  
Dying Cells ◽  
Dose Dependent

AbstractDendritic cells (DCs) are specialized antigen-presenting cells residing in tissues, from which they take up antigen. Activated DCs migrate through chemokine gradients from sites of inflammation to lymph nodes to stimulate T cells. At sites of inflammation, nucleotides, such as adenosine triphosphate (ATP), are released by activated or dying cells and can function as signaling molecules through P2 receptors (P2Rs). We investigated P2R expression in different DC populations and the effect of nucleotides on chemokine-directed migration. Exposure of monocyte-derived DCs (MoDCs) and CD1a+ dermal DCs to gradients of ATP inhibited their migratory capacity in a dose-dependent manner. Studies using P2R agonists and antagonists implicated signaling through the P2Y11R. On maturation, MoDCs down-regulated P2Y11R expression and were less sensitive to ATP-mediated inhibition of migration. In contrast, ATP did not inhibit the migration of CD1c+ peripheral blood (PB) DCs or interleukin-3 receptor-positive (IL-3R+) plasmacytoid DCs. Although all 4 DC populations expressed mRNA for P2Y11R, calcium-flux studies showed that blood DC types were unresponsive to P2Y11R agonists. In conclusion, DCs use distinct subtypes of P2R. The formation of ATP gradients at sites of inflammation may transiently inhibit the migration of local DCs, thus prolonging the time of antigen encounter. P2R inhibition may represent a new strategy to improve the migration of antigen-loaded DCs from the vaccination site to lymph nodes.

scholarly journals Boronic Acids of Pharmaceutical Importance Affect the Growth and Photosynthetic Apparatus of Cyanobacteria in a Dose-Dependent Manner

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 793
Author(s):  
Emilia Niemczyk ◽  
Jerzy Pogrzeba ◽  
Agnieszka Adamczyk-Woźniak ◽  
Jacek Lipok
Keyword(s):  
Photosynthetic Apparatus ◽  
Boronic Acids ◽  
Model Organisms ◽  
Commercial Application ◽  
Dependent Manner ◽  
Key Factor ◽  
Potential Impact ◽  
First Time ◽  
Dose Dependent ◽  
Derivatives Of

The dynamic increase in the commercial application of antimicrobial derivatives of boronic acids, and potential impact of their presence in aquatic systems, supports the necessity to study the toxicity of these substances towards microorganisms of crucial meaning in the environment. One example of the mentioned derivatives is tavaborole (5-fluoro-substituted benzoxaborole), a pharmaceutical agent with antifungal activity. Cyanobacteria were used as model organisms, which are photoautotrophic prokaryotes, as representative aquatic bacteria and photoautotrophs associated with the plant kingdom. To the best of our knowledge, we investigated this issue for the first time. In order to recognize the under-stress response of those microorganisms, the concentration of photopigments—a key factor in the activity of photosynthetic apparatus—was measured spectrophotometrically. We found that the 3-piperazine bis(benzoxaborole) significantly suppressed the growth of halophilic and freshwater cyanobacteria, at a concentration 3.0 mM and 0.3 mM, respectively. Our results also showed that the tested substances at micromolar concentrations stimulated the growth of cyanobacteria, particularly in the freshwater strain Chroococcidiopsis thermalis. The tested substances acted with various strengths, depending on their structure and concentration; nevertheless, they had a greater influence on the synthesis of phycobiliproteins (e.g., lowered their concentration) than on the formation of chlorophyll and carotenoids.

The Effect of Intravenous Adenosine Diphosphate on the Number of Circulating Platelets in Experimental Animals: Inhibition by Prostaglandin E1, Dipyridamole, SH-869 and VK-774

1977 ◽  
Vol 37 (01) ◽  
pp. 036-046 ◽  
Author(s):  
Ian B. Holmes ◽  
Gordon M. Smith ◽  
Franz Freuler
Keyword(s):  
Prostaglandin E1 ◽  
Potent Inhibitor ◽  
Adenosine Diphosphate ◽  
Dependent Manner ◽  
Response Curves ◽  
Duration Of Action ◽  
Intravenous Infusions ◽  
Long Duration ◽  
Dose Dependent ◽  
Derivatives Of

SummaryThe number of circulating platelets was monitored in anaesthetized animals by a continuous flow technique, using a Technicon Autocounter®. Intravenous infusions of adenosine diphosphate (ADP) produced transient, dose-dependent falls in circulating platelet numbers in rabbits, dogs, rats, pigs and squirrel monkeys. The rat was the most sensitive of the species investigated.In the rabbit, the effect of a submaximal dose of ADP was inhibited in a dose-dependent manner by intravenous infusions of prostaglandin E1 (PGE1), dipyridamole, and two derivatives of dipyridamole (SH-869 and VK-774). The dose-response curves for PGEl, SH-869 and VK-774 were approximately parallel, whereas that for dipyridamole was considerably less steep. PGE1 was the most potent inhibitor, but the duration of action was very short. Dipyridamole and SH-869 produced inhibition of long duration. The duration of action of VK-774 was intermediate.All inhibitors produced marked and often long-lasting hypotension. The fact that no inhibition of ADP effects could be demonstrated with dibenzyline and hexamethonium, which also produced marked hypotension of long duration, indicated that inhibition of the ADP effect by the four antagonists studied was not due to changes in blood pressure.

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