scholarly journals Synthesis, In Vitro Screening and Docking Studies of New Thiosemicarbazide Derivatives as Antitubercular Agents

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 251 ◽  
Author(s):  
Monika Pitucha ◽  
Zbigniew Karczmarzyk ◽  
Marta Swatko-Ossor ◽  
Waldemar Wysocki ◽  
Maciej Wos ◽  
...  
Keyword(s):  
Spectroscopic Analysis ◽  
Inhibitory Concentration ◽  
Acid Hydrazide ◽  
Docking Studies ◽  
Molecular Structures ◽  
Conformational Preference ◽  
X Ray ◽  
Carboxylic Acid Hydrazide ◽  
Thiosemicarbazide Derivatives

A series of thiosemicarbazide derivatives was designed and synthesized by reaction of carboxylic acid hydrazide with isothiocyanates. The molecular structures of the investigated thiosemicarbazides were confirmed and characterized by spectroscopic analysis. The conformational preference of carbonylthiosemicarbazide chain and intra- and intermolecular interactions in the crystalline state were characterized using X-ray analysis. The antituberculosis activity of the target compounds were tested in vitro against four Mycobacterium strains: M. H37Ra, M. phlei, M. smegmatis, M. timereck. The most active compounds were those with 2-pyridine ring. They exhibited lower minimal inhibitory concentration (MIC) values in the range 7.81–31.25 μg/mL in comparison to the other isomers. Compound 5 had activity against M. smegmatis at a concentration of 7.81 μg/mL whereas compound 2 had activity against all tested strains at a concentration of 15.625 μg/mL. The molecular docking studies were performed for investigated compounds using the Mycobacterium tuberculosis glutamine synthetase MtGS as their molecular target.

scholarly journals New Application of 1,2,4-Triazole Derivatives as Antitubercular Agents. Structure, In Vitro Screening and Docking Studies

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6033
Author(s):  
Zbigniew Karczmarzyk ◽  
Marta Swatko-Ossor ◽  
Waldemar Wysocki ◽  
Monika Drozd ◽  
Grazyna Ginalska ◽  
...  
Keyword(s):  
Degrees Of Freedom ◽  
Dipole Moments ◽  
Triazole Ring ◽  
Antimycobacterial Activity ◽  
Docking Studies ◽  
Molecular Structures ◽  
In Vitro Test ◽  
X Ray ◽  
Triazole Derivatives

A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures for analyzed 1,2,4-triazol-5-thione derivatives. The conformational preferences resulting from rotational degrees of freedom of the 1,2,4-triazole ring substituents were characterized. The lipophilicity (logP) and electronic parameters as the energy of frontier orbitals, dipole moments, NBO net charge distribution on the atoms, and electrostatic potential distribution for all structures were calculated at AM1 and DFT/B3LYP/6-311++G(d,p) level. The in vitro test was done against M. tuberculosis H37Ra, M. phlei, M. smegmatis, and M. timereck. The obtained results clearly confirmed the antituberculosis potential of compound C4, which turned out to be the most active against Mycobacterium H37Ra (MIC = 0.976 μg/mL), Mycobaterium pheli (MIC = 7.81 μg/mL) and Mycobacerium timereck (62.6 μg/mL). Satisfactory results were obtained with compounds C8, C11, C14 versus Myc. H37Ra, Myc. pheli, Myc. timereck (MIC = 31.25−62.5 μg/mL). The molecular docking studies were carried out for all investigated compounds using the Mycobacterium tuberculosis cytochrome P450 CYP121 enzyme as molecular a target connected with antimycobacterial activity.

Salaterpene E, a eudesmane-type sesquiterpene from Salacia longipes var. camerunensis

2016 ◽  
Vol 71 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Brice Mittérant Mba’ning ◽  
Bruno Lenta Ndjakou ◽  
Ferdinand Mouafo Talontsi ◽  
Alain Meli Lannang ◽  
Birger Dittrich ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Absolute Configuration ◽  
Previous Investigation ◽  
Spectroscopic Analysis ◽  
Inhibitory Concentration ◽  
Anomalous Scattering ◽  
X Ray Diffraction ◽  
Meoh Extract ◽  
X Ray

AbstractA mixture of two compounds with potent antiplasmodial activity in vitro against the W2 strain of Plasmodium falciparum (half maximal inhibitory concentration, 1.12 μg/mL) was obtained in a previous investigation of the CH2Cl2-MeOH extract of the seeds of Salacia longipes var. camerunensis. Separation by column chromatography led now to the isolation of salaterpene E (1) and (1R,2R,4S,5S,6R,7R,9S,10R)-2-acetoxy-1,6,9-tribenzoyloxy-4-hydroxy-dihydro-β-agarofuran (2). The structure of 1 was elucidated by spectroscopic analysis, and its absolute configuration was established unambiguously by means of single-crystal X-ray diffraction. Also the absolute configurations of the recently described salaterpenes A (2a) and D (2b) were determined by this method using the anomalous scattering of the oxygen atoms only.

scholarly journals Nitro/Nitrosyl-Ruthenium Complexes Are Potent and Selective Anti-Trypanosoma cruzi Agents Causing Autophagy and Necrotic Parasite Death

2014 ◽  
Vol 58 (10) ◽  
pp. 6044-6055 ◽  
Author(s):  
Tanira M. Bastos ◽  
Marília I. F. Barbosa ◽  
Monize M. da Silva ◽  
José W. da C. Júnior ◽  
Cássio S. Meira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Inhibitory Concentration ◽  
Content Type ◽  
X Ray ◽  
X Ray Crystallography ◽  
Ruthenium Nitrosyl ◽  
Index Analysis ◽  
Antiparasitic Drug ◽  
Drug Complex

ABSTRACTcis-[RuCl(NO2)(dppb)(5,5′-mebipy)] (complex 1),cis-[Ru(NO2)2(dppb)(5,5′-mebipy)] (complex 2),ct-[RuCl(NO)(dppb)(5,5′-mebipy)](PF6)2(complex 3), andcc-[RuCl(NO)(dppb)(5,5′-mebipy)](PF6)2(complex 4), where 5,5′-mebipy is 5,5′-dimethyl-2,2′-bipyridine and dppb is 1,4-bis(diphenylphosphino)butane, were synthesized and characterized. The structure of complex 2 was determined by X-ray crystallography. These complexes exhibited a higher anti-Trypanosoma cruziactivity than benznidazole, the current antiparasitic drug. Complex 3 was the most potent, displaying a 50% effective concentration (EC50) of 2.1 ± 0.6 μM against trypomastigotes and a 50% inhibitory concentration (IC50) of 1.3 ± 0.2 μM against amastigotes, while it displayed a 50% cytotoxic concentration (CC50) of 51.4 ± 0.2 μM in macrophages. It was observed that the nitrosyl complex 3, but not its analog lacking the nitrosyl group, releases nitric oxide into parasite cells. This release has a diminished effect on the trypanosomal protease cruzain but induces substantial parasite autophagy, which is followed by a series of irreversible morphological impairments to the parasites and finally results in cell death by necrosis. In infected mice, orally administered complex 3 (five times at a dose of 75 μmol/kg of body weight) reduced blood parasitemia and increased the survival rate of the mice. Combination index analysis of complex 3 indicated that itsin vitroactivity against trypomastigotes is synergic with benznidazole. In addition, drug combination enhanced efficacy in infected mice, suggesting that ruthenium-nitrosyl complexes are potential constituents for drug combinations.

Synthesis and antimicrobial activity of aryldiazenyl/arylhydrazono pyrazoles

2021 ◽  
Vol 45 (11-12) ◽  
pp. 1093-1099
Author(s):  
Abdulrhman Alsayari ◽  
Yahya I Asiri ◽  
Abdullatif Bin Muhsinah ◽  
Mohd. Zaheen Hassan
Keyword(s):  
Active Site ◽  
Phenyl Ring ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Docking Studies ◽  
Considerable Effect ◽  
Design Synthesis ◽  
Structure Activity ◽  
Antimicrobial Evaluation

We report the design, synthesis, and in vitro antimicrobial evaluation of functionalized pyrazoles containing a hydrazono/diazenyl moiety. Among these newly synthesized derivatives, 4-[2-(4-chlorophenyl)hydrazono]-5-methyl-2-[2-(naphthalen-2-yloxy)acetyl]-2,4-dihydro-3 H-pyrazol-3-one is a promising antimicrobial agent against Staphylococcus aureus (minimum inhibitory concentration 0.19 μg mL−1). Structure–activity relationship studies reveal that the electronic environment on the distal phenyl ring has a considerable effect on the antimicrobial potential of the hybrid analogues. Molecular docking studies into the active site of S. aureus dihydrofolate reductase also prove the usefulness of hybridizing a pyrazole moiety with azo and hydrazo groups in the design of new antimicrobial agents.

scholarly journals A droplet reactor on a super-hydrophobic surface allows control and characterization of amyloid fibril growth

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Peng Zhang ◽  
Manola Moretti ◽  
Marco Allione ◽  
Yuansi Tian ◽  
Javier Ordonez-Loza ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Hydrophobic Surface ◽  
Light Sheet ◽  
Molecular Structures ◽  
Structure Characterization ◽  
X Ray ◽  
Light Sheet Microscopy ◽  
Protein Fibrils ◽  
Dynamics Simulations

AbstractMethods to produce protein amyloid fibrils, in vitro, and in situ structure characterization, are of primary importance in biology, medicine, and pharmacology. We first demonstrated the droplet on a super-hydrophobic substrate as the reactor to produce protein amyloid fibrils with real-time monitoring of the growth process by using combined light-sheet microscopy and thermal imaging. The molecular structures were characterized by Raman spectroscopy, X-ray diffraction and X-ray scattering. We demonstrated that the convective flow induced by the temperature gradient of the sample is the main driving force in the growth of well-ordered protein fibrils. Particular attention was devoted to PHF6 peptide and full-length Tau441 protein to form amyloid fibrils. By a combined experimental with the molecular dynamics simulations, the conformational polymorphism of these amyloid fibrils were characterized. The study provided a feasible procedure to optimize the amyloid fibrils formation and characterizations of other types of proteins in future studies.

scholarly journals Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

2019 ◽  
Vol 15 ◽  
pp. 2631-2643 ◽  
Author(s):  
Heather J Lacey ◽  
Cameron L M Gilchrist ◽  
Andrew Crombie ◽  
John A Kalaitzis ◽  
Daniel Vuong ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Biosynthetic Pathway ◽  
Spectroscopic Analysis ◽  
Bioinformatics Analysis ◽  
Biosynthetic Gene Cluster ◽  
In Vitro Activity ◽  
X Ray Diffraction ◽  
X Ray ◽  
Drimane Sesquiterpenoids

Chemical investigation of an undescribed Australian fungus, Aspergillus nanangensis, led to the identification of the nanangenines – a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines.

scholarly journals Poly Organotin Acetates against DNA with Possible Implementation on Human Breast Cancer

2018 ◽  
Vol 19 (7) ◽  
pp. 2055 ◽  
Author(s):  
George Latsis ◽  
Christina Banti ◽  
Nikolaos Kourkoumelis ◽  
Constantina Papatriantafyllopoulou ◽  
Nikos Panagiotou ◽  
...  
Keyword(s):  
Binding Constants ◽  
Fetal Lung ◽  
Biological Properties ◽  
Docking Studies ◽  
Molecular Structures ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
X Ray Diffraction ◽  
Ct Dna

Two known tin-based polymers of formula {[R3Sn(CH3COO)]n} where R = n-Bu– (1) and R = Ph– (2),were evaluated for their in vitro biological properties. The compounds were characterized via their physical properties and FT-IR, 119Sn Mössbauer, and 1H NMR spectroscopic data. The molecular structures were confirmed by single-crystal X-Ray diffraction crystallography. The geometry around the tin(IV) ion is trigonal bi-pyramidal. Variations in O–Sn–O···Sn′ torsion angles lead to zig-zag and helical supramolecular assemblies for 1 and 2, respectively. The in vitro cell viability against human breast adenocarcinoma cancer cell lines: MCF-7 positive to estrogens receptors (ERs) and MDA-MB-231 negative to ERs upon their incubation with 1 and 2 was investigated. Their toxicity has been studied against normal human fetal lung fibroblast cells (MRC-5). Compounds 1 and 2 exhibit 134 and 223-fold respectively stronger antiproliferative activity against MDA-MB-231 than cisplatin. The type of the cell death caused by 1 or 2 was also determined using flow cytometry assay. The binding affinity of 1 and 2 towards the CT-DNA was suspected from the differentiation of the viscosity which occurred in the solution containing increasing amounts of 1 and 2. Changes in fluorescent emission light of Ethidium bromide (EB) in the presence of DNA confirmed the intercalation mode of interactions into DNA of both complexes 1 and 2 which have been ascertained from viscosity measurements. The corresponding apparent binding constants (Kapp) of 1 and 2 towards CT-DNA calculated through fluorescence spectra are 4.9 × 104 (1) and 7.3 × 104 (2) M−1 respectively. Finally, the type of DNA binding interactions with 1 and 2 was confirmed by docking studies.

Synthesis, Structure, and Antibacterial Activity of Novel 5-Arylpyrazole Derivatives

2008 ◽  
Vol 61 (3) ◽  
pp. 223 ◽  
Author(s):  
Xin-Hua Liu ◽  
Peng-Cheng Lv ◽  
Bo Li ◽  
Hai-Liang Zhu ◽  
Bao-An Song
Keyword(s):  
Experimental Data ◽  
Inhibitory Concentration ◽  
Positive Control ◽  
Significant Activity ◽  
X Ray ◽  
Subtilis Atcc ◽  
Bacillus Subtilis Atcc ◽  
And Staphylococcus Aureus ◽  
Antibacterial Potential

A series of novel 1-(acetyl,carboxamide,carbothioamide)substituted-5-(substituted-phenyl)-3-methy-4,5-dihydropyrazole derivatives have been synthesized and characterized by 1H NMR, IR, ESI-MS, and elemental analysis. Compounds 6h and 6q were further characterized by single crystal X-ray structural analysis. All of the compounds have been screened for their antibacterial potential in vitro against Bacillus subtilis ATCC 6633, Escherichia coli ATCC 35218, Pseudomonas fluorescens ATCC 13525, and Staphylococcus aureus ATCC 6538. Among the tested compounds, some of them display significant activity against the tested strains, and compounds 5ac and 6h show potent activity with a minimum inhibitory concentration value of 1.562 μg mL–1 against B. subtilis ATCC 6633, which is comparable to the positive control penicillin. Structure–effect relationships are also discussed based on the experimental data.

scholarly journals Cavity-Containing [Fe2L3]4+ Helicates: An Examination of Host-Guest Chemistry and Cytotoxicity

2021 ◽  
Vol 9 ◽  
Author(s):  
Lynn S. Lisboa ◽  
Mie Riisom ◽  
Roan A. S. Vasdev ◽  
Stephen M. F. Jamieson ◽  
L. James Wright ◽  
...  
Keyword(s):  
Cell Lines ◽  
Molecular Structures ◽  
Ionization Mass ◽  
Antiproliferative Effects ◽  
X Ray ◽  
X Ray Crystallography ◽  
H Nmr ◽  
Drug Molecules ◽  
Guest Chemistry

Two new di(2,2′-bipyridine) ligands, 2,6-bis([2,2′-bipyridin]-5-ylethynyl)pyridine (L1) and bis(4-([2,2′-bipyridin]-5-ylethynyl)phenyl)methane (L2) were synthesized and used to generate two metallosupramolecular [Fe2(L)3](BF4)4 cylinders. The ligands and cylinders were characterized using elemental analysis, electrospray ionization mass spectrometry, UV-vis, 1H-, 13C and DOSY nuclear magnetic resonance (NMR) spectroscopies. The molecular structures of the [Fe2(L)3](BF4)4 cylinders were confirmed using X-ray crystallography. Both the [Fe2(L1)3](BF4)4 and [Fe2(L2)3](BF4)4 complexes crystallized as racemic (rac) mixtures of the ΔΔ (P) and ΛΛ (M) helicates. However, 1H NMR spectra showed that in solution the larger [Fe2(L2)3](BF4)4 was a mixture of the rac-ΔΔ/ΛΛ and meso-ΔΛ isomers. The host-guest chemistry of the helicates, which both feature a central cavity, was examined with several small drug molecules. However, none of the potential guests were found to bind within the helicates. In vitro cytotoxicity assays demonstrated that both helicates were active against four cancer cell lines. The smaller [Fe2(L1)3](BF4)4 system displayed low μM activity against the HCT116 (IC50 = 7.1 ± 0.5 μM) and NCI-H460 (IC50 = 4.9 ± 0.4 μM) cancer cells. While the antiproliferative effects against all the cell lines examined were less than the well-known anticancer drug cisplatin, their modes of action would be expected to be very different.

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