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1.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37513881

RESUMO

Benzimidazoles are classified as a category of heterocyclic compounds. Molecules having benzimidazole motifs show promising utility in organic and scientific studies. A series of mono-substituted benzimidazoles were synthesized by ZnO-NPs via cyclocondensation between substituted aromatic aldehydes and o-phenylene diamine. The synthesized compounds were characterized and compared with the traditional methods. The nano-catalyzed method displayed a higher yield, shorter time and recyclable catalyst. The DFT study and antioxidant activity were investigated for benzo[d]imidazole derivatives. Compound 2a exhibited the highest antioxidant activity among the tested compounds. We focused on the catalytic activity of ZnO in the synthesis of heterocyclic structures with the goal of stimulating further progress in this field. The superiorities of this procedure are high yield of product, low amounts of catalyst and short reaction time.

2.
Bioorg Chem ; 136: 106560, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37121108

RESUMO

In this work, a novel promising hybrid mode of uracil/thiouracil based quinoline pharmacophore i.e. 5a-f was rationalized and synthesized based on rigidification and lipophilic principles, and following the reported pharmacophoric features of camptothecin & doxorubicin. Concurrently, a non-rigid mode pharmacophore i.e. 7a-f was also designed and synthesized. The anti-proliferative activity of the compounds was assessed against three different cancer cell lines, namely A549 lung cancer, MCF-7 breast adenocarcinoma, and HepG-2 hepatic carcinoma. Further, promising candidates were evaluated against A549, and MCF-7 and for their ability to inhibit topoisomerases I &II. Compound 5f was observed to be the most active congener, displaying the highest cell inhibition of 84.4% for topoisomerase I and 92%, for topoisomerase II at a concentration of 100 µM. When its cytotoxicity was evaluated against A549 cells, 5f arrested the cell cycle at the S phase and increased the apoptosis ratio by 46.31%. DFT calculation of 5f showed higher dipole moment and greater negative energy values (-247531.510 kcal/mol) with positive & negative poles, and better stability reflection. Furthermore, molecular docking of 5f to both enzymes showed good agreement with the biological assessment. This study has given insight for further consideration of the highly promising hybrid 5f.


Assuntos
Antineoplásicos , Quinolinas , Estrutura Molecular , Relação Estrutura-Atividade , Tiouracila/farmacologia , Simulação de Acoplamento Molecular , Uracila/farmacologia , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores da Topoisomerase II/farmacologia , Quinolinas/farmacologia , Proliferação de Células , Linhagem Celular Tumoral , DNA Topoisomerases Tipo II/metabolismo
3.
Bioorg Chem ; 131: 106280, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36436418

RESUMO

Polycyclic structures fused at a central carbon are of great interest due to their appealing conformational features and their structural implications in biological systems. Although progress in the development of synthetic methodologies toward such structures has been impressive, the stereo selective construction of such quaternary stereo centers remains a significant challenge in the total synthesis of natural products. From the computational calculations by Density Functional Theory along with the B3LYP as basis set, It is obvious that the all studied compounds are soft molecules and η varied from 0.069 for compound (10) to 0.087 for compound (15), while the compound (14) is treated as hard molecule, the value of η is 0.102, also the electronic transition within the soft compounds is easy as indicated from the △E, the compound (10) is absolute soft according to the (σ = 14.49 eV), while the compound (14) is treated as hard compounds (σ = 9.804 eV). The newly formed compounds exhibited both anti-inflammatory and antioxidant activities on HRBC homolytic and membrane stabilization and DPPH scavenging percent, respectively.


Assuntos
Antioxidantes , Teoria da Densidade Funcional , Conformação Molecular , Antioxidantes/farmacologia
4.
Int J Mol Sci ; 22(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34681643

RESUMO

Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives 2a-c as a key intermediate. The corresponding xanthine 3-5 and imidazolone derivatives 6-13 were obtained via reaction of oxazolone derivative 2a-c with 5,6-diaminouracils 1a-e under various conditions. Xanthine compounds 3-5 were obtained by cyclocondensation of 5,6-diaminouracils 1a-c with different oxazolones in glacial acetic acid. Moreover, 5,6-diaminouracils 1a-e were reacted with oxazolones 2a-c in presence of drops of acetic acid under fused condition yielding the imidazolone derivatives 6-13. Furthermore, Schiff base of compounds 14-16 were obtained by condensing 5,6-diaminouracils 1a,b,e with 4-dimethylaminobenzaldehyde in acetic acid. The structural identity of the resulting compounds was resolved by IR, 1H-, 13C-NMR and Mass spectral analyses. The novel synthesized compounds were screened for their antifungal and antibacterial activities. Compounds 3, 6, 13 and 16 displayed the highest activity against Escherichia coli as revealed from the IC50 values (1.8-1.9 µg/mL). The compound 16 displayed a significant antifungal activity against Candia albicans (0.82 µg/mL), Aspergillus flavus (1.2 µg/mL) comparing to authentic antibiotics. From the TEM microgram, the compounds 3, 12, 13 and 16 exhibited a strong deformation to the cellular entities, by interfering with the cell membrane components, causing cytosol leakage, cellular shrinkage and irregularity to the cell shape. In addition, docking study for the most promising antimicrobial tested compounds depicted high binding affinity against acyl carrier protein domain from a fungal type I polyketide synthase (ACP), and Baumannii penicillin- binding protein (PBP). Moreover, compound 12 showed high drug- likeness, and excellent pharmacokinetics, which needs to be in focus for further antimicrobial drug development. The most promising antimicrobial compounds underwent theoretical investigation using DFT calculation.


Assuntos
Anti-Infecciosos/síntese química , Imidazóis/química , Uracila/química , Xantinas/química , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Sítios de Ligação , Candida albicans/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , DNA Girase/química , DNA Girase/metabolismo , Teoria da Densidade Funcional , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Meia-Vida , Imidazóis/metabolismo , Imidazóis/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Policetídeo Sintases/química , Policetídeo Sintases/metabolismo , Relação Estrutura-Atividade , Termodinâmica , Células Vero
5.
Bioorg Chem ; 114: 105136, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34328860

RESUMO

Pyranopyrazole and its derivatives are classified to be a pharmacologically significant active scaffold for almost all modes of biological activities. In this work, An efficient, green, and facile three-component reaction for preparing pyrano[2,3-c]pyrazole derivatives via the condensation reaction of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, ethyl acetoacetate, and malononitrile in the presence of ZnO Nanoparticle. The products are produced with high yields and in shorter reaction times. It also is mild, safe, green, and environmentally friendly. The geometric parameters such as dipole moment, bond length, dihedral angles, total energy, heat of formation, atomic charges and energies at a highly accurate for prepared compounds were computed by Denisty Functional Theory along with the B3LYP functional. The newly synthesized compounds were screened for their anti-inflammatory and antioxidant activity. Some of the tested compounds displayed promising activities. The newly prepared compounds were found to be potent towards the antioxidant activity. Results indicated that compounds 11 and 12 exhibited significant (p ≥ 0.05) in vitro total antioxidant activity as 44.93 ± 0.15 and 39.60 ± 0.10 U/ML, respectively higher than standard ascorbic acid (29.40 ± 0.62).


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Teoria da Densidade Funcional , Inibidores de Lipoxigenase/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antioxidantes/síntese química , Antioxidantes/química , Araquidonato 5-Lipoxigenase/metabolismo , Catálise , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Humanos , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/química , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/metabolismo , Piranos/síntese química , Piranos/química , Piranos/farmacologia , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
6.
Molecules ; 26(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803210

RESUMO

Recently, the design of new biological metal-ligand complexes has gained a special interest all over the world. In this research, new series of mixed ligand complexes from meloxicam (H2mel) and glycine (Gly) were synthesized. Structures of the compounds were investigated employing elemental analyses, infrared, electronic absorption, 1H NMR, thermal analyses, effective magnetic moment and conductivity. The estimated molar conductivity of the compounds in 1 × 10-3 M DMF solution indicates the non-electrolyte existence of the examined complexes. Additionally, the effective magnetic moment values refer to the complexes found as octahedral molecular geometry. The data of the infrared spectra showed the chelation of H2mel and Gly with metal ions from amide oxygen and nitrogen of the thyizol groups of H2mel and through nitrogen of the amide group and oxygen of the carboxylic group for Gly. Thermal analyses indicated that the new complexes have good thermal stability and initially lose hydration water molecules followed by coordinated water molecules, Gly and H2mel. The kinetic parameters were calculated graphically using Coats-Redfern and Horowitz-Metzeger methods at n = 1 and n ≠ 1. The density functional theory (DFT) calculations were performed at B3LYP levels. The optimized geometry of the ligand and its complexes were obtained based on the optimized structures. The data indicated that the complexes are soft with η value in the range 0.114 to 0.086, while η = 0.140 for free H2mel. The new prepared complexes were investigated as antibacterial and antifungal agents against some phyto- and human pathogens and the minimum inhibitory concentration (MIC) data showed that complex (A) has the lowest MIC for Listeria and E. coli (10.8 µg/mL).


Assuntos
Meloxicam/química , Meloxicam/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Complexos de Coordenação/química , Escherichia coli/efeitos dos fármacos , Íons , Cinética , Ligantes , Espectroscopia de Ressonância Magnética/métodos , Meloxicam/síntese química , Metais/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Bases de Schiff/química , Espectrofotometria Infravermelho/métodos , Termodinâmica
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 199: 290-300, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29627613

RESUMO

The Zr(IV), Ce(IV) and U(VI) piroxicam anti-inflammatory drug complexes were prepared and characterized using elemental analyses, conductance, IR, UV-Vis, magnetic moment, IHNMR and thermal analysis. The ratio of metal: Pir is found to be 1:2 in all complexes estimated by using molar ratio method. The conductance data reveal that Zr(IV) and U(VI) chelates are non-electrolytes except Ce(IV) complex is electrolyte. Infrared spectroscopic confirm that the Pir behaves as a bidentate ligand co-ordinated to the metal ions via the oxygen and nitrogen atoms of ν(CO)carbonyl and ν(CN)pyridyl, respectively. The kinetic parameters of thermogravimetric and its differential, such as activation energy, entropy of activation, enthalpy of activation, and Gibbs free energy evaluated using Coats-Redfern and Horowitz-Metzger equations for Pir and complexes. The geometry of the piroxicam drug in the Free State differs significantly from that in the metal complex. In the time of metal ion-drug bond formation the drug switches-on from the closed structure (equilibrium geometry) to the open one. The antimicrobial tests were assessed towards some types of bacteria and fungi. The in vitro cell cytotoxicity of the complexes in comparison with Pir against colon carcinoma (HCT-116) cell line was measured.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Cério/química , Complexos de Coordenação/farmacologia , Piroxicam/química , Urânio/química , Zircônio/química , Anti-Infecciosos/química , Antineoplásicos/química , Bactérias/efeitos dos fármacos , Complexos de Coordenação/química , Fungos/efeitos dos fármacos , Células HCT116 , Humanos , Teoria Quântica , Termodinâmica
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 129: 519-36, 2014 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-24762540

RESUMO

The preparation and characterization of the new solid complexes [VO(CIP)2L]SO4⋅nH2O, where L=aniline (An), dimethylformamide (DMF), pyridine (Py) and triethylamine (Et3N) in the reaction of ciprofloxacin (CIP) with VO(SO4)2·2H2O in ethanol. The isolated complexes have been characterized with their melting points, elemental analysis, IR spectroscopy, magnetic properties, conductance measurements, UV-Vis. and (1)H NMR spectroscopic methods and thermal analyses. The results supported the formation of the complexes and indicated that ciprofloxacin reacts as a bidentate ligand bound to the vanadium ion through the pyridone oxygen and one carboxylato oxygen. The activation energies, E(*); entropies, ΔS(*); enthalpies, ΔH(*); Gibbs free energies, ΔG(*), of the thermal decomposition reactions have been derived from thermo gravimetric (TGA) and differential thermo gravimetric (DTG) curves, using Coats-Redfern and Horowitz-Metzeger methods. The lowest energy model structure of each complex has been proposed by using the density functional theory (DFT) at the B3LYP/CEP-31G level of theory. The ligand and their metal complexes were also evaluated for their antibacterial activity against several bacterial species, such as Bacillus Subtilis (B. Subtilis), Staphylococcus aureus (S. aureus), Nesseria Gonorrhoeae (N. Gonorrhoeae), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli).


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Ciprofloxacina/análogos & derivados , Ciprofloxacina/farmacologia , Vanádio/química , Vanádio/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Humanos , Análise Espectral
9.
Artigo em Inglês | MEDLINE | ID: mdl-21208824

RESUMO

The preparation and characterization of the new solid complexes [Y(CIP)2(H2O)2]Cl(3)·10H2O and [ZrO(CIP)2Cl]Cl·15H2O formed in the reaction of ciprofloxacin (CIP) with YCl3 and ZrOCl(2)·8H2O in ethanol and methanol, respectively, at room temperature were reported. The isolated complexes have been characterized with elemental analysis, IR spectroscopy, conductance measurements, UV-vis and 1H NMR spectroscopic methods and thermal analyses. The results support the formation of the complexes and indicate that ciprofloxacin reacts as a bidentate ligand bound to the metal ion through the pyridone oxygen and one carboxylato oxygen. The activation energies, E*; entropies, ΔS*; enthalpies, ΔH*; Gibbs free energies, ΔG*, of the thermal decomposition reactions have been derived from thermogravimetric (TGA) and differential thermogravimetric (DTG) curves, using Coats-Redfern and Horowitz-Metzeger methods. The proposed structure of the two complexes was detected by using the density functional theory (DFT) at the B3LYP/CEP-31G level of theory. The ligand as well as their metal complexes was also evaluated for their antibacterial activity against several bacterial species, such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) and antifungal screening was studied against two species (Penicillium (P. rotatum) and Trichoderma (T. sp.)). This study showed that the metal complexes are more antibacterial as compared to free ligand and no antifungal activity observed for ligand and their complexes.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Ciprofloxacina/química , Ciprofloxacina/farmacologia , Ítrio/farmacologia , Zircônio/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Cinética , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Temperatura , Termogravimetria
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