Nimbolide from Azadirachta indica and its derivatives plus first-generation cephalosporin antibiotics: a novel drug combination for wound-infecting pathogens

RSC Advances ◽  
2015 ◽  
Vol 5 (109) ◽  
pp. 89503-89514 ◽  
Author(s):  
S. R. Dhanya ◽  
S. Nishanth Kumar ◽  
Vandana Sankar ◽  
K. G. Raghu ◽  
B. S. Dileep Kumar ◽  
...  
Keyword(s):  
Azadirachta Indica ◽  
Drug Combination ◽  
First Generation ◽  
Bacterial Pathogens ◽  
Generation Cephalosporin ◽  
Amide Derivatives ◽  
Cephalosporin Antibiotics ◽  
Novel Drug ◽  
Derivatives Of

We evaluate the in vitro efficacy of nimbolide, desacetylnimbin, and the amide derivatives of nimbolide in combination with first-generation cephalosporin antibiotics against major wound-associated bacterial pathogens.

scholarly journals Deteksi Resistensi Fluorokuinolon di Salmonella sp dengan Menggunakan Uji Kepekaan Asam Nalidiksat

2016 ◽  
Vol 18 (1) ◽  
pp. 30
Author(s):  
Lim Bing Tiam ◽  
Tjan Sian Hwa ◽  
Sri Mulyani ◽  
Widiyani Widiyani ◽  
Diyah Asmawati ◽  
...  
Keyword(s):  
Nalidixic Acid ◽  
First Generation ◽  
Acid Resistance ◽  
High Sensitivity ◽  
Generation Cephalosporin ◽  
Fluoroquinolone Resistance ◽  
Diffusion Method ◽  
First Line ◽  
Line Drug

Fluoroquinolone is used as first line drug for Salmonella sp infection, but there were reports of increasing treatment failure with fluoroquinolone in infection caused by Salmonella sp, which in vitro is still succeptible to fluoroquinolone. The identification of nalidixic acid resistance, a first generation quinolone provides a high sensitivity and specifity for the detection of such fluoroquinolone resistance. The researchers aim is to study the prevalence and the minimum ciprofloxacin inhibitory concentration of nalidixic acid resistant but fluoroquinolone sensitive Salmonella sp at Premier Jatinegara Hospital. Blood cultures sent to Premier Jatinegara Hospital Laboratory during 2010 were evaluated according to Clinical and Laboratory Standards Institute guidelines. Identification and MIC succeptibility testing were determined by VITEK® 2 Compact (Biomerieux®) and nalidixic acid succeptibility testing was performed by disc diffusion method according to Kirby Bauer. Thirty eight Salmonella sp isolates were identified, all were succeptible to ciprofloxacin (MIC  0,25 mg/L), but 5 (13,2%) isolates were resistant to nalidixic acid and reported as resistant. This study found that 13,2% of Salmonella sp were resistant to fluoroquinolone but not detected by the recommended CLSI breakpoint values. The researchers recommend that nalidixic acid testing be included in Salmonella sp succeptibility testing in Indonesia and consider 3rd generation cephalosporin as the first line drug before a succeptibility test result is available.

scholarly journals Сationic carboxamide derivatives of tricyclic heteroaromatic compounds: synthesis and preliminary evaluation of antiproliferative activity

2020 ◽  
Vol 15 (1) ◽  
pp. 34-41
Author(s):  
Valentina Kostina ◽  
Inna Alexeeva ◽  
Nadia Lysenko ◽  
Valentina Negrutska ◽  
Igor Dubey
Keyword(s):  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Preliminary Evaluation ◽  
Heteroaromatic Compounds ◽  
Biological Targets ◽  
Amide Derivatives ◽  
Tumor Cell Culture ◽  
Intercalating Agents ◽  
Derivatives Of

This research was aimed at the synthesis and study of biological activity of the carboxamides of tricyclic heteroaromatic systems, acridone, phenazine and thioxanthone, containing the aliphatic and aromatic cationic substituents at amide fragment. These heterocyclic cores are DNA intercalating agents, whereas the introduction of cationic groups provides additional ionic interactions of the ligands with their biological targets, such as DNA and enzymatic complexes of the system of nucleic acids biosynthesis. A convenient way of the introduction of such groups is a modification of heterocyclic carboxamides. A small library of new cationic amide derivatives of acridone-4-, phenazine-1- and thioxanthone-4-carboxylic acids was obtained. They were synthesized in 37-81% yield by mild and selective quaternization of the nitrogen atoms at N,N-dimethylaminoalkyl (alkyl = ethyl, propyl) and pyridylmethyl fragments of the neutral N-functionalized carboxamides with methyl iodide. Tricyclic heteroaromatic cores were not affected. Convenient protocol for the synthesis of thioxanthone-4-carboxylic acid (TCA) based on the reaction of 2-mercaptobenzoic and 2-iodobenzoic acids followed by cyclization of the intermediate was developed (yield 79%). A series of new N-functionalized neutral amides of TCA, the precursors of corresponding cationic carboxamide, were also obtained via the reaction of acyl chloride with amines. Preliminary in vitro testing of four compounds as potential antitumor agents in U87MG tumor cell culture (human malignant glioma) demonstrated their significant antiproliferative activity at low micromolar concentrations, with growth inhibition values GI50 in the range 1.7-11 µM. These results suggest that cationic carboxamides of tricyclic heteroaromatic systems are promising scaffolds for the design of new antitumor drugs.

Amide derivatives of Gallic acid: Design, synthesis and evaluation of inhibitory activities against in vitro α-synuclein aggregation

2020 ◽  
Vol 28 (15) ◽  
pp. 115596
Author(s):  
Li Chen ◽  
Guo-Long Huang ◽  
Ming-Huan Lü ◽  
Yun-Xiao Zhang ◽  
Ji Xu ◽  
...  
Keyword(s):  
Gallic Acid ◽  
Design Synthesis ◽  
Amide Derivatives ◽  
Inhibitory Activities ◽  
Derivatives Of

Design and Synthesis of Some Novel Aromatic Amide Derivatives of Nilutamide as In Vitro Anticancer Agents

2020 ◽  
Vol 5 (39) ◽  
pp. 12317-12319
Author(s):  
Narasimha Swamy Thirukovela ◽  
Satheesh Kumar Nukala ◽  
Narsimha Sirassu ◽  
Ravinder Manchal ◽  
Prasad Gundepaka ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Design And Synthesis ◽  
Amide Derivatives ◽  
Aromatic Amide ◽  
Derivatives Of

scholarly journals MOLECULAR DOCKING OF SELECTED BIOACTIVE COMPOUNDS FROM AZADIRACHTA INDICA FOR THE INHIBITION OF COVID19 PROTEASE

2020 ◽  
pp. 71-77
Author(s):  
S. FEBINA BERNICE SHARON
Keyword(s):  
Bioactive Compounds ◽  
Azadirachta Indica ◽  
Binding Energies ◽  
Global Public Health ◽  
Lipinski’S Rule ◽  
Novel Drug ◽  
Native Ligand ◽  
Autodock 4.2

Objective: COVID-19 caused by novel SARS-coronavirus 2 belonging to family Coronaviridae, is a global public health emergency infecting many people all around the world, especially in India with more than 2,98,000 cases. Hence there is a need for a novel drug that counters SARS-CoV2 is the prime requirement at this time. Methods: The present study aimed to assess bioactive compounds found in Azadirachta indica as a potential inhibitor of COVID-19 Mpr °(6Y2E, 6LU7, and 2GTB) by Autodock 4.2, with the Lamarckian Genetic Algorithm. COVID-19 Mpr ° was docked with thirteen bioactive compounds, and docking was analyzed by Autodock 4.2 and Pymol. Nelfinavir and Saquinavir were used as positive standards for comparison. Results: Azadirachtanin, Azadirachtol, and Salannolide, were left out because of the violation of Lipinski’s rule. The binding energies obtained from the docking of 6Y2E with a native ligand, Azadiradione, Beta-sitosterol, Epiazadiradione, Epoxyazadiradione, Kaempferol, Meldenin, Myricetin, Nimbaflavone, Nimbinene, Nimbione, Nimbocinolide, Quercitrin, Vepnin, Saquinavir, and Nelfinavir were-7.32,-6.63,-6.69,-7.52,-5.27,-4.54,-6.07,-4.19,-5.02,-5.58,-6.23,-4.71, -3.72,-6.4,-7.14 and-4.67 kcal/mol respectively. The binding energies obtained from the docking of 6LU7 with the native ligand, Azadiradione, Nimbione, Vepnin, and Saquinavir were-6.14,-6.48,-6.79 and-6.49 kcal/mol correspondingly. The binding energies obtained from the docking of 2GTB with the native ligand, Azadiradione, Epiazadiradione, Epoxyazadiradione, Kaempferol, Meldenin, Myricetin, Nimbaflavone, Nimbione, Nimbocinolide, Quercitrin, Vepnin, Saquinavir, and Nelfinavir were-6.96,-7.13,-6.69,-5.22,-6.44,-5.06,-5.93,-6.66,-5.3,-5.63,-7.11,-6.89 and-5.42kcal/mol, respectively. Conclusion: Azadiradione, Epiazadiradione, Nimbione, and Vepnin seemed to have the greatest potential to act as COVID-19 protease inhibitors. However, further research is necessary to explore their prospective medicinal use in vitro and in vivo conditions.

Immobilization of Thrombin Inhibitors on Polyesters Surface: An Original Approach towards Materials Blood Compatibilization

2006 ◽  
Vol 514-516 ◽  
pp. 961-965 ◽  
Author(s):  
Claudio Salvagnini ◽  
Jacqueline Marchand-Brynaert
Keyword(s):  
Photoelectron Spectroscopy ◽  
Thrombin Inhibitors ◽  
Aromatic Azide ◽  
Poly Ethylene Terephthalate ◽  
Amide Derivatives ◽  
Human Thrombin ◽  
Coagulation Assay ◽  
Poly Ethylene ◽  
Derivatives Of

Piperazinyl-amide derivatives of N--(3-trifluoromethyl-benzenesulfonyl)-L-arginine were synthesized as graftable thrombin inhibitors. Their biological activity was evaluated in vitro, against human -thrombin, and in blood coagulation assay. The piperazinyl-amide derivatives were found to inhibit the activity of -thrombin in the micromolar range. The designed molecules were fixed on poly(ethylene terephthalate) (PET), and poly(butylene terephthalate) (PBT) by wet chemistry treatment (activation of hydroxyl chain-ends) and photochemistry (nitrene insertion by photoactivation of aromatic azide). The protocols were validated by X-ray photoelectron spectroscopy (XPS) and by radiochemical assay (liquid scintillation counting, LSC).

Fatty acyl amide derivatives of doxorubicin: Synthesis and in vitro anticancer activities

2011 ◽  
Vol 46 (6) ◽  
pp. 2037-2042 ◽  
Author(s):  
Bhupender S. Chhikara ◽  
Nicole St. Jean ◽  
Deendayal Mandal ◽  
Anil Kumar ◽  
Keykavous Parang
Keyword(s):  
Fatty Acyl ◽  
Anticancer Activities ◽  
Amide Derivatives ◽  
Acyl Amide ◽  
Derivatives Of

scholarly journals Synthesis and evaluation trypanosomicidal activity of new derivatives of megazol

2018 ◽  
Vol 5 (2) ◽  
pp. 40
Author(s):  
Helena B. Leites ◽  
Flávia S. Damasceno ◽  
Ariel M. Silber ◽  
Ronaldo Z. Mendonça ◽  
Cristina Northfleet de Albuquerque
Keyword(s):  
Cell Proliferation ◽  
Positive Control ◽  
In Vitro Test ◽  
Biological Part ◽  
Amide Derivatives ◽  
Vitro Test ◽  
South Americans ◽  
Derivatives Of

Objective: This work aims at the synthesis of megazol analogs with antitrypanosomicidal activity. Chagas’disease is caused by Trypanosoma cruzi and is a debilitating disease that has both acute and chronic forms. Many South Americans suffer from the chronic form of Chagas’disease, and there is no treatment currently available.Methods: In the chemical part, classical techniques of heterocyclic synthesis as well as usual methods of identification were used. In the biological part the cell proliferation test was used in vitro and the IC 50.Results: We synthesized a series of derivatives of 2-(1-methyl-5-nitro-2-imidazolyl)-5-substituted-1,3,4-thiadiazoles where 1-acetyl, 1-propyl and 1-nonyl were used as the substituent (4,6,7). Derivatives without nitro group were also synthesized (3,12) along with thiosemicarbazones (8,9,10) and a 5-(5-nitro-2-furanyl)-1,3,4-thiadiazol-2-amine (11). These compounds were evaluated using an in vitro test where were measured the cell proliferation. The derivatives that obtained the best results underwent further tests, in which their IC50 was calculated. The data revealed that two compounds (4,6) were effective against the parasite (IC50= 0.354 µM; IC50= 2.13 µM) and besides that, obtained the same results as the positive control, antimycim and rotenone. All proposed structures were obtained in satisfactory yields and purities.Conclusions: In conclusion, the in vitro trypanocidal activity makes these compounds promising leads in the development of an effective therapeutic agent. However, this study must be completed by additional tests with in vitro amastigote/macrophage models or in vivo mouse models. Analyzing the amide derivatives, compounds (4) and (6) were the ones that presented the best results.

A new class of 5-HT1A receptor antagonists with procognitive and antidepressant properties

2021 ◽  
Author(s):  
Agnieszka Jankowska ◽  
Grzegorz Satała ◽  
Artur Świerczek ◽  
Krzysztof Pociecha ◽  
Anna Partyka ◽  
...  
Keyword(s):  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Functional Profile ◽  
Receptor Antagonists ◽  
Receptor Affinity ◽  
New Class ◽  
Amide Derivatives ◽  
Derivatives Of

Aims: 5-HT1A receptor antagonists constitute a potential group of drugs in the treatment of CNS diseases. The aim of this study was to search for new procognitive and antidepressant drugs among amide derivatives of aminoalkanoic acids with 5-HT1A receptor antagonistic properties. Materials & methods: Thirty-three amides were designed and evaluated in silico for their drug-likeness. The synthesized compounds were tested in vitro for their 5-HT1A receptor affinity and functional profile. Moreover, their selectivity over 5-HT7, 5-HT2A and D2 receptors and ability to inhibit phosphodiesterases were evaluated. Results: A selected 5-HT1A receptor antagonist 20 ( Ki = 35 nM, Kb = 4.9 nM) showed procognitive and antidepressant activity in vivo. Conclusion: Novel 5-HT1A receptor antagonists were discovered and shown as potential psychotropic drugs.

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