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1.
Biometals ; 35(1): 159-171, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34993713

RESUMO

In this report 5 compounds were synthesized and structural and their photophysical characterization was performed (ΦΔ and Φf). Furthermore, in this in vitro study, their biological activity against Leishmania panamensis was evaluated. The photophysical behavior of these compounds was measured and high ΦΔ and low Φf was observed. Besides, DFT quantum calculations on the electronic structures were performed. Finally, the biological activity was determined by means of the compounds capacity to inhibit the viability of parasites using the MTT assay. The inclusion of the metal ions substantially modified the photophysical and biological properties in comparison with the free metal porphyrin (1). In fact, Zn2+ porphyrin derivative (2) showed a marked decrease of Φf and increase of ΦΔ. In this sense, using TDDFT approaches, a luminescent process for Sn4+ derivative (3) was described, where emissive states involve the ML-LCT transition. So, this led to a decrease in the singlet oxygen production (0.82-0.67). Biological results showed that all compounds inhibit the viability of L. panamensis with high efficiency; the decrease in the viability was greater as the concentration of exposure increased. Finally, under light irradiation the IC50 of L. panamensis against the Zn(II)-porphyrin (2) and V(IV)-porphyrin (5) was lower than the IC50 of the Glucantime control (IC50 = 2.2 and 6.95 µM Vs IC50 = 12.7 µM, respectively). We showed that the use of porphyrin and metalloporphyrin-type photosensitizers with exceptional photophysical properties can be successful in photodynamic therapy (PDT) against L. panamensis, being the diamagnetic ion Zn2+ a candidate for the preparation of metalloporphyrins with high singlet oxygen production.


Assuntos
Leishmania , Metaloporfirinas , Fotoquimioterapia , Porfirinas , Metaloporfirinas/química , Metaloporfirinas/farmacologia , Metais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Oxigênio Singlete/química , Zinco/farmacologia
2.
Int J Mol Sci ; 21(1)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861333

RESUMO

A series of 44 hybrid compounds that included in their structure tetrahydroquinoline (THQ) and isoxazole/isoxazoline moieties were synthesized through the 1,3-dipolar cycloaddition reaction (1,3-DC) from the corresponding N-allyl/propargyl THQs, previously obtained via cationic Povarov reaction. In vitro cholinergic enzymes inhibition potential of all compounds was tested. Enzyme inhibition assays showed that some hybrids exhibited significant potency to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Especially, the hybrid compound 5n presented the more effective inhibition against AChE (4.24 µM) with an acceptable selectivity index versus BChE (SI: 5.19), while compound 6aa exhibited the greatest inhibition activity on BChE (3.97 µM) and a significant selectivity index against AChE (SI: 0.04). Kinetic studies were carried out for compounds with greater inhibitory activity of cholinesterases. Structure-activity relationships of the molecular hybrids were analyzed, through computational models using a molecular cross-docking algorithm and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding free energy approach, which indicated a good correlation between the experimental inhibition values and the predicted free binding energy.


Assuntos
Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Isoxazóis/química , Quinolinas/química , Acetilcolinesterase/química , Sítios de Ligação , Domínio Catalítico , Técnicas de Química Sintética , Inibidores da Colinesterase/síntese química , Ativação Enzimática/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
3.
Chem Sci ; 15(30): 12042-12046, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39092125

RESUMO

Highly selective formal [4 + 2]-cycloaddition of vinyldiazoacetates with azoalkenes from α-halohydrazones, as well as with cyclopentadiene and furan, occurs with light irradiation at room temperature, producing highly functionalized heterocyclic and bicyclic compounds in good yields and excellent diastereoseletivity. Under blue light these vinyldiazoacetate reagents selectively form unstable cyclopropenes that undergo intermolecular cycloaddition reactions at a faster rate than their competitive ene dimerization. [4 + 2]-cycloaddition of vinyldiazoacetates with in situ formed azoalkenes produces bicyclo[4.1.0]tetrahydropyridazine derivatives and, together with their cycloaddition using cyclopentadiene and furan that form tricyclic compounds, they occur with high chemoselectivity and diastereocontrol, good functional group tolerance, and excellent scalability. Subsequent transformations portray the synthetic versatility of these structures.

4.
Nanomaterials (Basel) ; 14(6)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38535647

RESUMO

In this study, two new nanohybrids (NH-A and NH-B) were synthesized through carbodiimide-assisted coupling. The reaction was performed between carboxymethyl-scleroglucans (CMS-A and CMS-B) with different degrees of substitution and commercial amino-functionalized silica nanoparticles using 4-(dimethylamino)-pyridine (DMAP) and N,N'-dicyclohexylcarbodiimide (DCC) as catalysts. The morphology and properties of the nanohybrids were investigated by using transmission (TEM) and scanning electron microscopy (SEM), electron-dispersive scanning (EDS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), inductively coupled plasma atomic emission spectroscopy (ICP-OES), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic light scattering (DLS). The nanohybrids exhibited differences in structure due to the incorporation of polyhedral oligomeric silsesquioxane (POSS) materials. The results reveal that hybrid nanomaterials exhibit similar thermal properties but differ in morphology, chemical structure, and crystallinity properties. Finally, a viscosity study was performed on the newly obtained nanohybrid materials; viscosities of nanohybrids increased significantly in comparison to the carboxymethyl-scleroglucans, with a viscosity difference of 7.2% for NH-A and up to 32.6% for NH-B.

5.
ChemMedChem ; 16(17): 2686-2694, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-33844464

RESUMO

Multidrug resistance (MDR) is one of the major factors in the failure of many chemotherapy approaches. In cancer cells, MDR is mainly associated with the expression of ABC transporters such as P-glycoprotein, MRP1 and ABCG2. Despite major efforts to develop new selective and potent inhibitors of ABC drug transporters, no ABCG2-specific inhibitors for clinical use are yet available. Here, we report the evaluation of sixteen tetrahydroquinoline/4,5-dihydroisoxazole derivatives as a new class of ABCG2 inhibitors. The affinity of the five best inhibitors was further investigated by the vanadate-sensitive ATPase assay. Molecular modelling data, proposing a potential binding mode, suggest that they can inhibit the ABCG2 activity by binding on site S1, previously reported as inhibitors binding region, as well targeting site S2, a selective region for substrates, and by specifically interacting with residues Asn436, Gln398, and Leu555. Altogether, this study provided new insights into THQ/4,5-dihydroisoxazole molecular hybrids, generating great potential for the development of novel most potent ABCG2 inhibitors.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Isoxazóis/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Quinolinas/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Isoxazóis/química , Modelos Moleculares , Estrutura Molecular , Proteínas de Neoplasias/metabolismo , Quinolinas/química , Relação Estrutura-Atividade
6.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 3): o680-1, 2010 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-21580425

RESUMO

The title compound, C(23)H(22)N(2), was obtained using the three-component imino Diels-Alder reaction via a one-pot condensation between anilines, α-pyridine-carboxy-aldehyde and indene using BF(3)·OEt(2) as the catalyst. The mol-ecular structure reveals the cis-form as the unique diastereoisomer. The crystal structure comprises one-dimensional zigzag ribbons connected via N-H⋯N hydrogen bonds. C-H⋯π inter-actions also occur.

7.
Mol Divers ; 10(1): 29-37, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16404527

RESUMO

New effective approach to the synthesis of a wide variety of C-2 nitro or aminophenyl substituted quinolines was reported using diverse intermediate 4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines that were prepared by a three component imino Diels-Alder reaction was reported. The key aromatisation process occurs cleanly with the loss of the 2-oxopyrrolinidyl-1 fragment.


Assuntos
Iminas/química , Quinolinas/síntese química , Ciclização , Conformação Molecular , Estrutura Molecular , Quinolinas/química , Estereoisomerismo
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