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

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.

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Anti-Inflammatory Effects of 3-Formyl, 7-Flavonols Derivatives by Microwave Enhanced Chemistry Assisted - Vilsmeier Haack Synthesis

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1809 ◽

2019 ◽

Vol 12 (04) ◽

pp. 1779-1791

Author(s):

M. Karpakavalli ◽

A.Y. Sangilimuthu ◽

A.Usha Raja Nanthini ◽

G.Nagaraja Perumal ◽

S. Mohan ◽

...

Keyword(s):

Protein Denaturation ◽

Population Increase ◽

Spectral Studies ◽

Dimethyl Formamide ◽

Mass Spectral ◽

Paw Oedema ◽

Rf Values ◽

Anti Inflammatory

In the modern medicines the novel and active molecules are essential to act against various diseases and increase the needs day by day due to population increase. In view of that, we attempt to make a variety of synthetic molecules against inflammation by a new and popular greener microwave assisted and faster method such as Microwave Enhanced Chemistry assisted Vilsmeier Haack Synthesis (MEC-VHS). In this paper, we report the synthesis of nitro- dinitro- and acetyl- derivatives of 3- formyl, 7-flavonols using MEC-VHS techniques against inflammation as anti-inflammatory agent. These derivatives were synthesized via pinkish formylation complex of dimethyl formamide and phosphorous oxychloride by microwave irradiation resulted as suspension by base. The re-crystallized products were characterized through Co-TLC, λmax, IR, HPTLC, 1HNMR, CHN analysis and mass spectral studies. The HPTLC finger print profiles obtained were of with a prominent single peak and with a matching Rf values compared to that obtained by an ordinary Co-TLC technique. All the synthesized compounds were screened for their anti-inflammatory activity by in vitro protein denaturation method and in vivo carrageenan induced paw oedema method and it was found that all the compounds excepting the un-substituted 3-formyl, 7-flavonols gave an equi- or more potent activity as compared to that of the standard.

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Synthesis, Spectral Studies, In Vitro Antimicrobial and In Vivo Multi-infection Antifungal Activities in Mice of New Organotin(iv) Derivatives of Amino Acids

Journal of Chemical Research Synopses ◽

10.1039/a800173a ◽

1998 ◽

pp. 409-409 ◽

Cited By ~ 13

Author(s):

Mala Nath ◽

Rakesh Yadav ◽

G. Eng ◽

P. Musingarimi

Keyword(s):

Amino Acids ◽

Spectral Studies ◽

Antifungal Activities ◽

Derivatives Of

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Synthesis, Characterization, and Thermal and Antimicrobial Activities of Some Novel Organotin(IV): Purine Base Complexes

Journal of Chemistry ◽

10.1155/2013/568195 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Reena Jain ◽

Rajeev Singh ◽

N. K. Kaushik

Keyword(s):

Antimicrobial Agents ◽

Rhizopus Oryzae ◽

Antimicrobial Activities ◽

Spectral Studies ◽

Purine Base ◽

Mass Spectral ◽

E Coli ◽

Kinetic And Thermodynamic Parameters ◽

C Nmr

A new series of organotin(IV) complexes with purine bases theophylline (HL1) and theobromine (L2) of the types R3Sn(L1), R2Sn(L1)Cl, R3Sn(L2)Cl, and R2Sn(L2)Cl2(R = C6H5CH2–;p-ClC6H4CH2–) have been synthesized in anhydrous THF. The complexes were characterized by elemental analysis, conductance measurements, molecular weight determinations, UV-vis, IR,1H,13C NMR, and mass spectral studies. Various kinetic and thermodynamic parameters of these complexes have also been determined using TG/DTA technique. The thermal decomposition techniques indicate the formation of SnO2as a residue. The results show that the ligands act as bidentate, forming a five-member chelate ring. All the complexes are 1 : 1 metal-ligand complexes. In order to assess their antimicrobial activity, the ligands and their corresponding complexes have also been testedin vitroagainst bacteria (E. coli, S. aureus, andP. pyocyanea) and fungi (Rhizopus oryzaeandAspergillus flavus). All the complexes exhibit remarkable activity, and the results provide evidence that the studied complexes might indeed be a potential source of antimicrobial agents.

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TetX Is a Flavin-dependent Monooxygenase Conferring Resistance to Tetracycline Antibiotics

Journal of Biological Chemistry ◽

10.1074/jbc.m409573200 ◽

2004 ◽

Vol 279 (50) ◽

pp. 52346-52352 ◽

Cited By ~ 155

Author(s):

Wangrong Yang ◽

Ian F. Moore ◽

Kalinka P. Koteva ◽

David C. Bareich ◽

Donald W. Hughes ◽

...

Keyword(s):

Antimicrobial Agents ◽

Anaerobic Bacteria ◽

Tetracycline Antibiotics ◽

Active Efflux ◽

Mass Spectral ◽

Nmr Characterization ◽

Antibiotic Degradation

The tetracycline antibiotics block microbial translation and constitute an important group of antimicrobial agents that find broad clinical utility. Resistance to this class of antibiotics is primarily the result of active efflux or ribosomal protection; however, a novel mechanism of resistance has been reported to be oxygen-dependent destruction of the drugs catalyzed by the enzyme TetX. Paradoxically, thetetXgenes have been identified on transposable elements found in anaerobic bacteria of the genusBacteroides. Overexpression of recombinant TetX inEscherichia colifollowed by protein purification revealed a stoichiometric complex with flavin adenine dinucleotide. Reconstitution ofin vitroenzyme activity demonstrated a broad tetracycline antibiotic spectrum and a requirement for molecular oxygen and NADPH in antibiotic degradation. The tetracycline products of TetX activity were unstable at neutral pH, but mass spectral and NMR characterization under acidic conditions supported initial monohydroxylation at position 11a followed by intramolecular cyclization and non-enzymatic breakdown to other undefined products. TetX is therefore a FAD-dependent monooxygenase. The enzyme not only catalyzed efficient degradation of a broad range of tetracycline analogues but also conferred resistance to these antibioticsin vivo. This is the first molecular characterization of an antibiotic-inactivating monooxygenase, the origins of which may lie in environmental bacteria.

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Synthesis and characterization of barbitones as antimicrobial agents

Journal of the Serbian Chemical Society ◽

10.2298/jsc0606587s ◽

2006 ◽

Vol 71 (6) ◽

pp. 587-591 ◽

Cited By ~ 6

Author(s):

H.G. Sangani ◽

K.B. Bhimani ◽

R.C. Khunt ◽

A.R. Parikh

Keyword(s):

Antimicrobial Activity ◽

Barbituric Acid ◽

Antimicrobial Agents ◽

Spectral Studies ◽

Synthesis And Characterization ◽

Mass Spectral ◽

Elemental Analyses ◽

Bacteria And Fungi

Barbitones (3) were synthesised by the condensation of chalcones (2) with barbituric acid. The structure of the synthesized compounds were assigned on the basis of elemental analyses, IR, NMR and mass spectral studies. All the products were evaluated for their in vitro antimicrobial activity against various strains of bacteria and fungi.

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Marine Peptide-N6NH2 and Its Derivative-GUON6NH2 Have Potent Antimicrobial Activity Against Intracellular Edwardsiella tarda in vitro and in vivo

Frontiers in Microbiology ◽

10.3389/fmicb.2021.637427 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huihui Han ◽

Da Teng ◽

Ruoyu Mao ◽

Ya Hao ◽

Na Yang ◽

...

Keyword(s):

Antimicrobial Agents ◽

Edwardsiella Tarda ◽

Microtubule Polymerization ◽

Antibiotic Effect ◽

Intracellular Activities ◽

Marine Peptide ◽

Derivatives Of ◽

Post Antibiotic Effect

Edwardsiella tarda is a facultative intracellular pathogen in humans and animals. There is no effective way except vaccine candidates to eradicate intracellular E. tarda. In this study, four derivatives of marine peptide-N6NH2 were designed by an introduction of unnatural residues or substitution of natural ones, and their intracellular activities against E. tarda were evaluated in macrophages and in mice, respectively. The minimum inhibitory concentration (MIC) value of N6NH2 and GUON6NH2 against E. tarda was 8 μg/mL. GUON6NH2 showed higher stability to trypsin, lower toxicity (<1%) and longer post-antibiotic effect (PAE) than N6NH2 and other derivatives. Antibacterial mechanism results showed that GUON6NH2 could bind to LPS and destroyed outer/inner cell membranes of E. tarda, superior to N6NH2 and norfloxacin. Both N6NH2 and GUON6NH2 were internalized into macrophages mainly via lipid rafts, micropinocytosis, and microtubule polymerization, respectively, and distributed in the cytoplasm. The intracellular inhibition rate of GUON6NH2 against E. tarda was 97.05–100%, higher than that in case of N6NH2 (96.82–100%). In the E. tarda-induced peritonitis mouse model, after treatment with of 1 μmol/kg N6NH2 and GUON6NH2, intracellular bacterial numbers were reduced by 1.54- and 1.97-Log10 CFU, respectively, higher than norfloxacin (0.35-Log10 CFU). These results suggest that GUON6NH2 may be an excellent candidate for novel antimicrobial agents to treat infectious diseases caused by intracellular E. tarda.

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Synthesis, spectral studies and in vitro antimicrobial activity of some new di/tri-organotin (IV) complexes of Schiff bases derived from 2-benzoylpyridine

Journal of the Serbian Chemical Society ◽

10.2298/jsc160429089k ◽

2017 ◽

Vol 82 (1) ◽

pp. 13-23 ◽

Cited By ~ 5

Author(s):

Priyanka Khatkar ◽

Sonika Asija ◽

Namita Singh

Keyword(s):

Schiff Bases ◽

Antimicrobial Agents ◽

Lipid Membrane ◽

Antimicrobial Activities ◽

Molar Ratio ◽

Spectral Studies ◽

Dilution Method ◽

Gram Positive ◽

Gram Negative

In the present work, a series of twenty-four organotin (IV) complexes of the type [R2SnLCl, R3SnL] have been synthesized by the condensation of 2-benzoylpyridine Schiff bases with R2SnCl2, R3SnCl (R= Me, n-Bu, Ph) in 1:1 molar ratio. These complexes were well characterized by IR, 1H, and 13C, 119Sn NMR, XRD and mass spectral techniques. In the search for biologically more effective antimicrobial agents, all the synthesized ligands and organotin complexes were evaluated for their in vitro antimicrobial activities against two Gram positive and two Gram negative bacteria, and two fungal strains by serial dilution method. The results of spectral data revealed that the complexes formed were hexacoordinated with tridentate ligands which coordinated through azomethine N, pyridine N and carboxylate O ligation sites. The ligands on co-ordination with tin metal showed a discernible augmentation in biocidal activity, however, the Ph and Bu complexes were found to be more intoxicating. The results revealed that the synthesized complexes were more noxious towards Gram positive strains as compared to Gram negative strains which may be attributed to the presence of an outer lipid membrane of lipopolysaccharides.

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Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

Current Bioactive Compounds ◽

10.2174/1573407214666180226130957 ◽

2019 ◽

Vol 15 (1) ◽

pp. 63-70

Author(s):

Shiv Dev Singh ◽

Arvind Kumar ◽

Firoz Babar ◽

Neetu Sachan ◽

Arun Kumar Sharma

Keyword(s):

Antimicrobial Activity ◽

Potassium Hydroxide ◽

Antimicrobial Agents ◽

Pyrimidine Ring ◽

Antimicrobial Activities ◽

Screening Methods ◽

Chlorpheniramine Maleate ◽

In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

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Derivatives of Deoxypodophyllotoxin Induce Apoptosis Through Bcl-2/Bax Proteins Expression

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999200730160952 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ya-Nan Li ◽

Ni Ning ◽

Lei Song ◽

Yun Geng ◽

Jun-Ting Fan ◽

...

Keyword(s):

Annexin V ◽

Mtt Method ◽

Anthriscus Sylvestris ◽

Anti Tumor Activity ◽

Derivatives Of ◽

Toxicity In Vitro ◽

Ht 29 ◽

Mcf 7

Background: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. Objective: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness.Methods:The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. Results: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. Conclusion: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

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