RESUMEN
New pseudonucleosides containing cyclic sulfamide moiety and sulfamoyl ß-D-glucosamine derivative are described. These pseudonucleosides are synthesized in good yields starting from chlorosulfonyl isocyanate and ß-D-glucosamine hydrochloride in five steps; (protection, acetylation, removal of the Boc group, sulfamoylation, and cyclization). Further, novel glycosylated sulfamoyloxazolidin-2-one is prepared in three steps; carbamoylation, sulfamoylation, and intramolecular cyclization. The structures of the synthesized compounds were confirmed by usual spectroscopic and spectrometric methods NMR, IR, MS, and EA. Interesting molecular docking of the prepared pseudonucleosides and (Beclabuvir, Remdesivir) drugs with SARS-CoV-2/Mpro (PDB:5R80) was conducted using the same parameters for a fair comparison. A low binding affinity of the synthesized compounds compared to the Beclabuvir and other analysis showed that pseudonucleosides have the ability to inhibit SARS-CoV-2. After the motivating results of molecular docking study, the complex between the SARS-CoV-2 Mpro and compound 7 was subjected to 100 ns molecular dynamics (MD) simulation using Desmond module of Schrodinger suite, during which the receptor-ligand complex showed substantial stability after 10 ns of MD simulation. Also, we studied the prediction of absorption, distribution, properties of metabolism, excretion, and toxicity (ADMET) of the synthesized compounds.Communicated by Ramaswamy H. Sarma.
Asunto(s)
COVID-19 , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Glicosilación , GlucosaminaRESUMEN
Photodynamic antimicrobial chemotherapy (PACT), as one of the promising alternative antimicrobial treatment, has received great attention in recent years. In this work, a new antimicrobial material has been elaborated by grafting a neutral porphyrin, the metallated 5-(4-azidophenyl)-10,15,20-triphenylporphyrin, onto lignocellulosic fibers by using the Copper (I)-Catalyzed Alkyne-Azide 1,3-dipolar Cycloaddition (CuAAC) reaction. The cross-linked porphyrin-Kraft pulp material was characterized by infrared and by XPS spectroscopy analyses, which proved the covalent linkage between the porphyrin and propargylated Kraft pulp fibers. The antimicrobial activity of this material was tested under visible light irradiation with a low light dose (9.5 J/cm(2)) against Staphylococcus aureus and Pseudomonas aeruginosa. The two bacterial strains deposited on the resulting photosensitizing Kraft pulp are efficiently killed after illumination. Such materials could find applications in industrial, household and medical environments as an alternative to overcome the widespread microbial multiresistance to classical treatments.
Asunto(s)
Lignina/química , Fármacos Fotosensibilizantes/química , Porfirinas/química , Alquinos/química , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Azidas/química , Catálisis , Cobre/química , Reacción de Cicloadición , Luz , Pruebas de Sensibilidad Microbiana , Espectroscopía de Fotoelectrones , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/farmacología , Porfirinas/síntesis química , Porfirinas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacosRESUMEN
This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H-[1,2,3]triazole, showed an interesting cytotoxic effect.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Química Clic , Citotoxinas/síntesis química , Citotoxinas/farmacología , Mecloretamina/análogos & derivados , Mecloretamina/síntesis química , Neoplasias/tratamiento farmacológico , Alquinos/química , Azidas/química , Catálisis , Cobre/química , Reacción de Cicloadición , Humanos , Mecloretamina/farmacología , Células Tumorales CultivadasRESUMEN
This paper deals with the synthesis of nitrogen mustard analogs, derivatives of purine bases. Alkylation in position N-9 and diethanolamine fixation on position 6 were managed by microwave irradiations. Chlorination of these dihydroxylated intermediates led to a cyclization, giving tricyclic purine base analogs bearing a chloroethyl chain. Finally, MTT assays on obtained compounds do not show cytotoxicity on four different cancer cell lines.
Asunto(s)
Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacología , Mecloretamina/análogos & derivados , Mecloretamina/farmacología , Purinas/química , Purinas/farmacología , Alquilación , Antineoplásicos Alquilantes/síntesis química , Línea Celular Tumoral , Supervivencia Celular , Halogenación , Humanos , Mecloretamina/síntesis química , Neoplasias/tratamiento farmacológico , Purinas/síntesis químicaRESUMEN
This work deals with the synthesis of a new nitrogen mustard derivative based on thymine. To introduce the bis(2-chloroethyl)amine group to position 4 of the pyrimidine base, many strategies were explored and the desired compound was finally obtained, thanks to a synthetic pathway in five steps.
Asunto(s)
Antineoplásicos Alquilantes/síntesis química , Mecloretamina/síntesis química , Timina/química , Alquilación , Antineoplásicos Alquilantes/química , Etanolaminas/química , Mecloretamina/química , Estructura MolecularRESUMEN
We have used a 104 MHz lithium tantalate (LiTaO(3)) surface acoustic wave (SAW) sensor to investigate DNA probes grafting and their further hybridization with natural and click generated (Cg-DNA) oligonucleotides. Natural DNA targets of different strand lengths, tosyl-di(tri, tetra) thymidine and azido-di(tri, tetra) thymidine oligonucleotides were tested. In our case, and besides the follow-up of a 34mer DNA hybridization, we detected complementarity between natural DNA probes and azido-tetra-thymidine for the first time, whereas previous hybridization studies reported a minimal of 10-mer oligonucleotides recognition length. We also demonstrated that contrarily to natural DNA, the synthesized oligonucleotides present stable bonds with complementary DNA strands. Frequency responses of both grafting and hybridization have shown the same shape: an exponential decay with different time constants, (187±1)s and (68±19) s for grafting and hybridization respectively. We have also shown that recognition between DNA strands and tetranucleotide analogues is comparable to natural 34mer DNA bases and presents the same time constant within uncertainties.
Asunto(s)
Técnicas Biosensibles/métodos , ADN/análisis , Hibridación de Ácido Nucleico , Acústica , Secuencia de Bases , Técnicas Biosensibles/instrumentación , ADN/genética , Sondas de ADN/química , Sondas de ADN/genética , Litio , Óxidos , TantalioRESUMEN
The synthesis of a new family of D4T analogues is described to study the influence of pyrazinone base on antiretroviral power. Substitution of 3H by methyl or n-decyl increases the lipophilic character and may facilitate diffusion across cell membranes. The compounds were characterized by (1)H NMR and infrared spectroscopy. Antiviral (HIV-1) properties of these compounds were examined.
Asunto(s)
Fármacos Anti-VIH/síntesis química , Nucleósidos/síntesis química , Pirazinas/química , Estavudina/química , Fármacos Anti-VIH/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Nucleósidos/químicaRESUMEN
The synthesis and biological activity of a novel DNA cross-linking antitumor agent is presented. The new alkylating agent significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.
Asunto(s)
Compuestos de Mostaza Nitrogenada/síntesis química , Compuestos de Mostaza Nitrogenada/farmacología , Timina/análogos & derivados , Antineoplásicos Alquilantes/síntesis química , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quimiotaxis/efectos de los fármacos , Humanos , Metaloproteinasa 2 de la Matriz , Inhibidores de la Metaloproteinasa de la Matriz , Invasividad Neoplásica/prevención & control , Compuestos de Mostaza Nitrogenada/química , Timina/química , Timina/farmacologíaRESUMEN
The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.
Asunto(s)
Antineoplásicos/síntesis química , Hidrocarburos Clorados/síntesis química , Nucleósidos de Pirimidina/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Hidrocarburos Clorados/química , Hidrocarburos Clorados/farmacología , Nucleósidos de Pirimidina/química , Nucleósidos de Pirimidina/farmacología , Neoplasias de la Vulva/tratamiento farmacológicoRESUMEN
This article describes the synthesis of a series of AZT analogues bearing an acyclic chain between the sugar and the base moieties is described. These new compounds were readily obtained using microwave irradiation. The compounds were characterized by (1)H NMR and IR spectroscopy. Antiviral (HIV-1) properties of these compounds were examined.
Asunto(s)
Antivirales/química , Nucleósidos/química , Zidovudina/química , Antivirales/síntesis química , Antivirales/farmacología , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , VIH-1/efectos de los fármacos , Humanos , Modelos Químicos , Estructura Molecular , Zidovudina/síntesis química , Zidovudina/farmacologíaRESUMEN
The synthesis of new acyclic nucleosides is described. These syntheses were accomplished by various methods: glycosylation, selective or total deprotection, oxidation/reduction, chlorination or azidation of hydroxyl groups. The compounds were characterized with NMR, mass and IR spectroscopy. Antiviral properties of these compounds were evaluated on HIV-1 infected cell lines.
Asunto(s)
Fármacos Anti-VIH/síntesis química , VIH-1 , Nucleósidos/síntesis química , Replicación Viral/efectos de los fármacos , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Nucleósidos/química , Nucleósidos/farmacologíaRESUMEN
Synthesis of 3'-3', 5-5', and 3'-5' dimeric thymidine, linked by an olefinic chain between glycosidic moieties is described. Cross metathesis reaction of 3' or 5' O-allyl analogues of thymidine led to the expected 3'-3' and 5'-5' dimeric compounds, respectively. In order to obtain the 3'-5' dimer, 5'-O-allyl and 3'-O-allyl monomers were first linked by their free 3' OH and 5' OH groups through a glutaryl spacer; ring closing metathesis was then operated upon this temporary dimer, followed by glutaryl removal.
Asunto(s)
Nucleósidos/química , Catálisis , Dimerización , Espectroscopía de Resonancia Magnética , Modelos Químicos , Conformación Molecular , Conformación de Ácido Nucleico , Ácidos Nucleicos/química , Nucleósidos/síntesis química , Timidina/químicaRESUMEN
The synthesis of a series of d4T analogues bearing an acyclic chains between the sugar and the base moities, is described. New compounds were obtained readily using microwave irradiation and selective deprotection of sugar part. The compounds were characterized by 1H NMR and IR spectroscopy. Antiviral (HIV-1) properties of these compounds were examined.
Asunto(s)
Inhibidores de la Transcriptasa Inversa/química , Estavudina/análogos & derivados , Línea Celular , VIH-1/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética , Inhibidores de la Transcriptasa Inversa/síntesis química , Inhibidores de la Transcriptasa Inversa/farmacología , Espectrofotometría Infrarroja , Estavudina/síntesis química , Estavudina/farmacologíaRESUMEN
Under mild conditions (Lewis acid/solvent/room temperature), the reaction of unprotected glucose, deoxyribose or xylose with hydroxylalkylthymine gives selectively nucleoside analogs with a spacer arm between sugar and base moiety. Experimental conditions (Lewis acid, solvent) for this new strategy leading to nucleoside analogs synthesis are discussed.
Asunto(s)
Carbohidratos/química , Nucleósidos de Pirimidina/síntesis química , Timina/análogos & derivados , Timina/química , Glicosilación , Nucleósidos de Pirimidina/químicaRESUMEN
An improved procedures for the synthesis of 5'-O-allylthymidine via one step selective allylation of thymidine using either ultrasound or microwave activation is described.