RESUMEN
AIMS: In this article, we have developed an eco-friendly one-pot multi-component reaction methodology employed for the green synthesis of functionalized pyrazole derivatives viz cyclo-condensation of aromatic aldehydes, ethyl acetoacetate and phenyl hydrazine and/or hydrazine hydrate in the presence of cetyltrimethylammoniumbromide (CTAB) at 90°C temperature in an aqueous medium. MATERIALS AND METHODS: In the present protocol, we developed a green method for the synthesis of functionalized pyrazole derivatives through one-pot, multi-component cyclo-condensation of aromatic aldehydes, phenyl hydrazine or hydrazine hydrate and ethyl acetoacetate using cetyltrimethylammoniumbromide (CTAB) as a catalyst in water as a solvent. Our methodology confers advantages such as short reaction time, atom economy, purification of the product without using column chromatographic and hazardous solvent. The reaction is being catalyzed by cetyltrimethylammoniumbromide (CTAB) and thus, products are formed under the green reaction conditions. RESULTS AND DISCUSSION: Initially, the reaction of benzaldehyde and phenylhydrazine with ethyl acetoacetate was carried out in water at room temperature in the absence of the catalyst; no product was obtained after 24 h (Table 1 entry 1). When the reaction was carried out using L-proline as a catalyst in ethanol at 70°C, the yield of the product was 20%. CONCLUSION: This research not only provides a green and efficient method for the synthesis of sulfinic esters but also shows new applications of electrochemistry in organic synthesis. We consider that this green and efficient synthetic protocol used to prepare sulfinic esters will have good applications in the future. In conclusion, we have developed successfully a green and efficient one-pot multi-component methodology for the synthesis of substituted pyrazoles using CTAB as a catalyst in water as a solvent with excellent yields. Purifications of compounds were achieved without the use of traditional chromatographic procedures. This methodology has advantages of operational simplicity, clean reaction profiles and relatively broad scope, which make it more attractive for the diversity oriented synthesis of these heterocyclic libraries. In this methodology, we suggest a further alternative possibility for the formation of substituted pyrazoles. The compound 7h can be used as an anticancer drug in the pharma industry.
Asunto(s)
Aldehídos , Pirazoles , Antibacterianos , Catálisis , Técnicas de Química SintéticaRESUMEN
Presently available medications for treatment of organiphosphorus poisoning are not sufficiently effective due to various pharmacological and toxicological reasons. In this regard, herein we report the synthesis of a series of N-thiazolylacetamide monoquaternary pyridinium oximes and its analogs (1a-1b to 6a-6b) with diversely substituted thiazole ring and evaluation of their in vitro reactivation efficacies against nerve agent (sarin, O-ethylsarin and VX) inhibited human erythrocyte acetylcholinesterase (hAChE). Reactivation kinetics was performed to determine dissociation constant (KD), reactivity rate constant (kr) and the second order rate constant (kr2) for all the compounds and compared their efficacies with commercial antidotes viz. 2-PAM and obidoxime. All the newly synthesized oximes were evaluated for their physicochemical parameters (pKa) and correlated with their respective reactivation efficacies to assess the capability of the oxime reactivator. Three of these novel compounds showed promising reactivation efficacies toward OP inhibited hAChE. Molecular docking studies were performed in order to correlate the reactivation efficacies with their interactions in the active site of the AChE.
Asunto(s)
Acetilcolinesterasa/química , Sustancias para la Guerra Química/química , Reactivadores de la Colinesterasa/síntesis química , Oximas/química , Acetilcolinesterasa/metabolismo , Sitios de Unión , Dominio Catalítico , Sustancias para la Guerra Química/metabolismo , Reactivadores de la Colinesterasa/química , Reactivadores de la Colinesterasa/metabolismo , Humanos , Cinética , Simulación del Acoplamiento Molecular , Compuestos Organotiofosforados/química , Compuestos Organotiofosforados/metabolismo , Oximas/síntesis química , Oximas/metabolismo , Compuestos de Piridinio/química , Sarín/análogos & derivados , Sarín/química , Sarín/metabolismo , Tiazoles/químicaRESUMEN
A series of mono pyridinium oximes linked with arenylacetamides as side chains were synthesized and their in vitro reactivation potential was evaluated against human acetylcholinesterase (hAChE) inhibited by organophosphorus inhibitors (OP) such as sarin, VX and tabun. The reactivation data of the synthesized compounds were compared with those obtained with standard reactivators such as 2-PAM and obidoxime. The dissociation constant (KD) and specific reactivity (kr) of the oximes were also determined by performing reactivation kinetics against OP inhibited hAChE. Among the synthesized compounds, oximes 1-(2-(4-cyanophenylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (12a) and 4-((hydroxyimino)methyl)-1-(2-(4-methoxyphenylamino)-2-oxoethyl)pyridinium chloride (2a) were found most potent reactivators for hAChE inhibited by sarin. In case of VX inhibited hAChE majority of the oximes have shown good reactivation efficacies. Among these oximes 1-(2-(benzylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (18a), 4-((hydroxyimino)methyl)-1-(2-(4-(methoxycarbonyl)phenylamino)-2-oxoethyl)pyridinium-chloride (14a) and 12a were found to surpass the reactivation potential of 2-PAM and obidoxime. However, the synthesized oximes showed marginal reactivation efficacies in case of tabun inhibited hAChE. The pKa value of the oximes were determined and correlated with their observed reactivation potential.
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Acetilcolinesterasa/efectos de los fármacos , Reactivadores de la Colinesterasa/síntesis química , Compuestos Organofosforados/farmacología , Oximas/síntesis química , Compuestos de Piridinio/síntesis química , Reactivadores de la Colinesterasa/farmacología , Humanos , Técnicas In Vitro , Cinética , Oximas/farmacología , Compuestos de Piridinio/farmacologíaRESUMEN
Herein we report the in-vitro controlled release properties of 1, 3, 5-trisubstituted-2-pyrazolines through Layer-by-Layer (LbL) self assembled thin films fabricated from chitosan and heparin sodium salt as biocompatible polyelectrolytes. This study was carried out as a preliminary step towards the applicability of LbL technique in prophylactic drug delivery of antimalarial drugs. The growth of LbL self assembly was monitored by UV-Visible spectrophotometry and Quartz Crystal Microbalance (QCM). The loading as well as in-vitro release studies (in phosphate buffer saline at pH 7.4) were carried out using UV-Visible spectroscopy. Three compounds having good antimalarial activity were tested and the release rate was found inversely proportional to the hydrophobicity of the drug. Pzln-4 has shown best release among all the three compounds (up to 780 min) followed by Pzln-5 and Pzln-8. The release trend was that of a fast release up to first 2 h followed by a steady release. Kinetic fitting of the data confirmed the process of drug release followed a pseudo second order kinetics (R(2)≥0.99). A large value of rate constant (k) revealed a faster release. Pzln-4 has shown smallest value of k corresponding to slowest release among all the three compounds.
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Antimaláricos/química , Quitosano/química , Preparaciones de Acción Retardada/química , Heparina/química , Pirazoles/química , Antimaláricos/síntesis química , Materiales Biocompatibles , Tampones (Química) , Liberación de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Pirazoles/síntesis química , Tecnicas de Microbalanza del Cristal de Cuarzo , SolucionesRESUMEN
A new series of 4-phenyldiazenyl 2-(phenylimino methyl) phenols were synthesized by the condensation of 5-[(2-chloro phenyl) diazenyl] 2-hydroxybenzaldehyde with different substituted aromatic amines and sulphonamides. All the synthesized compounds were screened in-vitro for their antibacterial activity against different human pathogens viz: B. anthracis, E.coli, S. aureus, S. typhimurium, and P. aeruginosa using disk diffusion assay. All the compounds exhibited considerable inhibition against the bacteria tested.
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Antibacterianos/síntesis química , Fenoles/síntesis química , Aminas , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Pruebas Antimicrobianas de Difusión por Disco , Humanos , Fenoles/farmacología , SulfonamidasRESUMEN
The increasing clinical importance of drug resistant microbial pathogens has lent additional urgency to microbiological research and new antimicrobial compound development. For this purpose, a new series of 3-[phenyldiazenyl] benzaldehyde N-phenylthiosemicarbazones were synthesized and evaluated for antifungal and antibacterial activity. The reaction of 2-hydroxy-5-[phenyldiazenyl] benzaldehyde (I) with N-phenylhydrazinecarbothioamide (II) were carried out in DMF. The antimicrobial activity of the synthesized target compounds (III) were evaluated by screening on different human pathogens using the disc diffusion assay. All the compounds exhibited considerable inhibition against the bacteria and fungi tested.
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Antibacterianos/síntesis química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/farmacología , Antibacterianos/química , Antifúngicos/química , Antifúngicos/farmacología , Benzaldehídos/química , Humanos , Iminas/química , Espectroscopía de Resonancia Magnética , Tiosemicarbazonas/químicaRESUMEN
A series of 3-chloro-4-(3-methoxy-4-acetyloxyphenyl)-1-[3-oxo-3-(phenylamino)propanamido] azetidin-2-ones 3a-g and 3-chloro-4-[2-hydroxy-5-(nitro substituted phenylazo)phenyl]-1-phenylazetidin-2-ones 6a-h were synthesized using appropriate synthetic route. Structures of all the synthesized compounds were established on the basis of elemental analysis and spectroscopic data. The antimicrobial activity of the synthesized compounds was screened against several microbes. Several of these molecules showed potent antimicrobial activity against Bacillus anthracis, Staphylococcus aureus and Candida albicans and significant structure-activity relationship (SAR) trends.