Synthesis of novel 1,3,4-oxadiazole derivatives of nicotinic acid and its in-vitro antithrombotic activity

2021 ◽  
pp. 431-434
Author(s):  
Vishal T. Khot ◽  
S. K. Mohite ◽  
C. S. Magdum
Keyword(s):  
Side Effects ◽  
Nicotinic Acid ◽  
Clot Formation ◽  
Activity Profile ◽  
Antithrombotic Activity ◽  
Oxadiazole Derivatives ◽  
Derivatives Of

The pharmacological characteristics of azole are diverse. Only a few medications can reduce the risk of clot formation, and they all have serious side effects. At present time there has to be more focus on to cure this type of complication beacause due to environmental, emotional, physical, other biological incidents are much related to this condition. Resistance has developed to existing medications, prompting the implementation of novel medications with a greater activity profile. The synthesis of a 1,3,4-oxadiazole derivative from nicotinic acid as well as its antithrombotic activity is described in this paper.

Inhibitors of Acetylcholinesterase Derived from 7-Methoxytacrine and Their Effects on the Choline Transporter CHT1

2016 ◽  
Vol 43 (1-2) ◽  
pp. 45-58 ◽  
Author(s):  
Zdenka Kristofikova ◽  
Jan Ricny ◽  
Ondrej Soukup ◽  
Jan Korabecny ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Side Effects ◽  
Amyloid Β ◽  
Acetylcholinesterase Inhibitors ◽  
Side Chain ◽  
Choline Transporter ◽  
Disease Therapy ◽  
Cortical Membranes ◽  
Derivatives Of

Background: Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. Methods: We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Results: Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. Conclusion: The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research.

scholarly journals New oxadiazole derivatives of isonicotinohydrazide in the search for antimicrobial agents: Synthesis and in vitro evaluation

2012 ◽  
Vol 77 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Manav Malhotra ◽  
Mohit Sanduja ◽  
Abdul Samad ◽  
Aakash Deep
Keyword(s):  
Antimicrobial Agents ◽  
Fungal Strain ◽  
Spectral Studies ◽  
Dilution Method ◽  
Mass Spectral ◽  
Oxadiazole Derivatives ◽  
Derivatives Of ◽  
And Staphylococcus Aureus

Structural modification of the front line antitubercular drug isoniazid provide a lipophilic adaptations of the drug in which hydrazide moiety of isoniazid is replaced by 1,3,4-oxadiazole heterocycles to eliminate in-vivo acetylation by arylamine N-acetyltransferase which results to form inactive acetylated drug. In the present study a series of sixteen oxadiazole derivatives were synthesized and characterized by (IR, 1H NMR, 13C NMR and Mass spectral) studies. All the synthesized compounds were evaluated for their antimicrobial activity by broth dilution method against two Gram positive strains (Bacillus subtilis and Staphylococcus aureus), two Gram negative strains (Pseudomonas aeruginosa and Escherichia coli) and fungal strain (Candida albicans and Aspergillus niger). The minimum inhibitory concentration of the compounds was in the range of 1.56-50 ?g ml-1 against bacterial and fungal strain. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Among the synthesized derivatives 4g, 4h, 4m and 4p were found to be most effective antimicrobial compounds.

Derivatives of 5-Aminolevulinic Acid for Photodynamic Therapy

2007 ◽  
Vol 1 ◽  
pp. 1177391X0700100 ◽  
Author(s):  
Ryan F. Donnelly ◽  
Paul A. McCarron ◽  
David A. Woolfson
Keyword(s):  
Photodynamic Therapy ◽  
Side Effects ◽  
Aminolevulinic Acid ◽  
Skin Lesions ◽  
Rational Approach ◽  
Topical Formulation ◽  
Systemic Bioavailability ◽  
Clinical Benefits ◽  
Derivatives Of

Photodynamic therapy (PDT) is a clinical treatment that combines the effects of visible light irradiation with subsequent biochemical events that arise from the presence of a photosensitising drug (possessing no dark toxicity) to cause destruction of selected cells. Today, the most common agent used in dermatological PDT is 5-aminolevulinic acid (ALA). As a result of its hydrophilic character, ALA penetrates skin lesions poorly when applied topically. Its systemic bioavailability is limited and it is known to cause significant side effects when given orally or intravenously. Numerous chemical derivatives of ALA have been synthesised with the aims of either improving topical penetration or enhancing systemic bioavailability, while reducing side effects. In vitro cell culture experiments with ALA derivatives have yielded promising results. However, if ALA derivatives are to demonstrate meaningful clinical benefits, a rational approach to topical formulation design is required, along with a systematic study aimed at uncovering the true potential of ALA derivatives in photodynamic therapy. With respect to systemic ALA delivery, more study is required in the developing area of ALA-containing dendrons and dendrimers.

scholarly journals Synthesis of Oxadiazolyl, Pyrazolyl and Thiazolyl Derivatives of Thiophene-2-Carboxamide as Antimicrobial and Anti-HCV Agents

2017 ◽  
Vol 11 (1) ◽  
pp. 38-53 ◽  
Author(s):  
Ola H. Rizk ◽  
Omaima G. Shaaban ◽  
Abeer E. Abdel Wahab
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Activities ◽  
Hcv Rna ◽  
Bacterial Strains ◽  
Low Concentration ◽  
Oxadiazole Derivatives ◽  
Polymerase Chain ◽  
New Compounds ◽  
Derivatives Of

Introduction: Three series of pyrazole, thiazole and 1,3,4-oxadiazole, derivatives were synthesized starting from 5-amino-4-(hydrazinocarbonyl)-3-methylthiophene-2-carboxamide (2). Methods: All compounds were investigated for their preliminary antimicrobial activity. They were proved to exhibit remarkable antimicrobial activity against Pseudomonas aeruginosa with insignificant activity towards Gram positive bacterial strains and fungi. Results: In-vitro testing of the new compounds on hepatitis-C virus (HCV) replication in hepatocellular carcinoma cell line HepG2 infected with the virus utilizing the reverse transcription polymerase chain reaction technique (RT-PCR) generally showed inhibition of the replication of HCV RNA (–) strands at low concentration, while, eight compounds; 3a, 6, 7a, 7b, 9a, 9b, 10a and 11b proved to inhibit the replication of HCV RNA (+) and (–) strands at very low concentration range 0.08-0.36 μg/mL. Conclusion: Compounds 7b and 11b displayed the highest anti-HCV and antimicrobial activities in this study.

scholarly journals Artemisone and Artemiside Control Acute and Reactivated Toxoplasmosis in a Murine Model

2009 ◽  
Vol 53 (10) ◽  
pp. 4450-4456 ◽  
Author(s):  
Ildiko R. Dunay ◽  
Wing Chi Chan ◽  
Richard K. Haynes ◽  
L. David Sibley
Keyword(s):  
Side Effects ◽  
Toxoplasma Gondii ◽  
Murine Model ◽  
Acute Infection ◽  
Immunocompromised Patients ◽  
Artemisinin Derivatives ◽  
Parasite Replication ◽  
Derivatives Of

ABSTRACT Immunocompromised patients are at risk of developing toxoplasmosis, and although chemotherapy is available, standard treatments are often complicated by severe side effects. Artemisinin is a new highly potent antimalarial drug that has activity against Toxoplasma gondii in vitro. However, artemisinin derivatives have previously been ineffective in vivo using a rat model of toxoplasmosis. In the present study, the efficacy of several new artemisinin derivates was investigated for treatment of mice infected with the parasite Toxoplasma gondii. Artemiside and artemisone displayed better inhibition than either artemisinin or artesunate against the parasite in vitro. Artemiside and artemisone treatment controlled parasite replication in vivo, and mice survived the acute infection. In a murine model of reactivated toxoplasmosis, both drugs increased survival, although artemiside was more effective. These results indicate that these newer derivatives of artemisinin may have potential for treatment of toxoplasmosis.

Design, synthesis and in vitro anticancer activity of novel quinoline and oxadiazole derivatives of ursolic acid

2017 ◽  
Vol 27 (17) ◽  
pp. 4128-4132 ◽  
Author(s):  
Wen Gu ◽  
Xiao-Yan Jin ◽  
Dong-Dong Li ◽  
Shi-Fa Wang ◽  
Xu-Bing Tao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Ursolic Acid ◽  
Design Synthesis ◽  
Oxadiazole Derivatives ◽  
Derivatives Of

scholarly journals In Vitro Inhibition of Toxoplasma gondii by Four New Derivatives of Artemisinin

2006 ◽  
Vol 50 (12) ◽  
pp. 4206-4208 ◽  
Author(s):  
Lorraine Jones-Brando ◽  
John D'Angelo ◽  
Gary H. Posner ◽  
Robert Yolken
Keyword(s):  
Cell Culture ◽  
Side Effects ◽  
Toxoplasma Gondii ◽  
In Vitro Inhibition ◽  
Derivatives Of

ABSTRACT Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is medically important and distributed worldwide. Currently available medications are limited in terms of efficacy and side effects. We synthesized novel, nonacetal, hydrolytically stable derivatives of artemisinin and showed that they inhibit the replication of Toxoplasma gondii in cell culture.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

A Thiazole Compound with Potential Antithrombotic Activity

1982 ◽  
Vol 47 (02) ◽  
pp. 173-176 ◽  
Author(s):  
E E Nishizawa ◽  
A R Mendoza ◽  
T Honohan ◽  
K A Annis
Keyword(s):  
Platelet Aggregation ◽  
Potent Inhibitor ◽  
Platelet Rich Plasma ◽  
Development Program ◽  
Antithrombotic Agent ◽  
Antithrombotic Activity ◽  
Thiazole Derivative ◽  
Cyclooxygenase Activity ◽  
Drug Development Program

SummaryA thiazole derivative, 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)-thiazole was found to be a potent inhibitor of collagen-induced platelet aggregation, in vitro, using platelets from at least six species, including man. It was active in human platelet-rich plasma at a concentration of 1 ng/ml. While its antiplatelet activity was greater than that of flurbiprofen, its cyclooxygenase activity was equivalent to that of flurbiprofen. Also, compared to flurbiprofen, the thiazole had less anti-inflammatory activity in the hind-paw edema test. The thiazole derivative inhibited platelet aggregation following oral administration in five laboratory species. In the guinea pig it was active at 0.5 mg/kg. The LD50 in mice was greater than 1000 mg/kg (i.p.). This compound, which was designed through a systematic drug development program, may have high potential as an antithrombotic agent.

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