MW-9, a chalcones derivative bearing heterocyclic moieties, ameliorates ulcerative colitis via regulating MAPK signaling pathway / 中国药理学通报

Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

Evaluación de la toxicidad de chalconas sintéticas con potencial anti-Leishmania en ratones BALB/c / Toxicity assessment of synthetic chalcones with antileishmanial potential in BALB/c mice

RESUMEN Objetivo: Evaluar la toxicidad de tres chalconas sintéticas administradas por vía intraperitoneal en ratones BALB/c. Materiales y métodos: La dosis letal media (DL50) se estimó por el método Up-and-Down de Dixon. La toxicidad subcrónica de las chalconas se evaluó a 20 y 40 mg/kg por 21 días. Se evaluó el efecto tóxico a nivel de comportamiento, fisiológico, bioquímico e histológico. Resultados: La chalcona 43 generó moco en las heces, daño visceral (hígado) y alteración en el coeficiente de órganos (riñón, p = 0,037 y cerebro, p = 0,008) en comparación con el grupo control. Además, en el análisis histológico se observó que esta chalcona produjo edema, inflamación y necrosis en los órganos evaluados, aunque no hubo diferencia significativa con el control. Todos los parámetros bioquímicos no difirieron significativamente entre los grupos de tratamiento a dosis de 40 mg/kg y el control. Conclusiones: La DL50 para las tres chalconas fue superior a 550 mg/kg de peso corporal. Las chalconas 40 y 42 son relativamente no tóxicas. Ambas pueden considerarse seguras para la aplicación vía intraperitoneal en ratones BALB/c y, en consecuencia, son posibles candidatas para ser usadas en el tratamiento contra las leishmaniosis.

ABSTRACT Objective: To evaluate the toxicity of three synthetic chalcones administered intraperitoneally to BALB/c mice. Materials and methods: The median lethal dose (LD50) was estimated by Dixon's Up-and-Down method. Subchronic toxicity of chalcones was evaluated at 20 and 40 mg/kg for 21 days. Behavioral, physiological, biochemical, and histological toxic effects were evaluated. Results: Chalcone 43 produced mucus in feces, visceral damage (liver) and alterations in organ coefficient (kidney, p = 0.037 and brain, p = 0.008) when compared to the control group. In addition, histological analysis showed that this chalcone produced edema, inflammation and necrosis in the evaluated organs, although there was no significant difference with the control. None of the biochemical parameters differed significantly between the treatment groups at 40 mg/kg dose and the control. Conclusions: The LD50 for all three chalcones was greater than 550 mg/kg of body weight. Chalcones 40 and 42 were found to be relatively non-toxic. Both can be considered safe for intraperitoneal application in BALB/c mice and, consequently, are potential candidates for use in the treatment of leishmaniasis.

A method for the synthesis of chalcones / 中国药科大学学报

@#In this paper,a new method for catalytic synthesis of chalcones from substituted acetophenone and substituted benzaldehyde in polyphosphoric acid/concentrated sulfuric acid system was proposed,and the reaction conditions were optimized. The results showed that the optimized reaction conditions were determined as polyphosphoric acid of 5 equiv. and concentrated sulfuric acid of 20 equiv.,with 1,4-dioxane as solvent at 90 °C for 2 h under nitrogen protection. Twelve chalcones were synthesized with good yield. All target compounds were characterized by IR,HRMS,1H NMR and 13C NMR.

Compostos carbonílicos α, ß-insaturados e hidrazonas sintéticas como antiparasitários / α, ß-Unsaturated carbonyl compounds and Synthetic hydrazones as antiparasitics

Apesar da grande relevância médica e social, e por serem responsáveis por grande parte das mortes em países subdesenvolvidos e em desenvolvimento as doenças negligenciadas (DN), ainda, não apresentam terapêutica eficaz. Dentre as diversas DN, doenças como a doença de Chagas, a Leishmaniose visceral e a malária, se destacam no cenário nacional, por terem alta incidência e prejuízos sociais. Os fármacos disponíveis para o tratamento destas parasitoses, apresentam alta toxicidade e, em alguns casos, resistência por parte dos parasitas. Assim sendo, faz-se necessário o planejamento e desenvolvimento de novos agentes quimioterápicos mais seguros e eficazes. Dentre as diferentes estratégias de planejamento de fármacos, selecionamos o planejamento de fármacos baseado na estrutura do ligante - LBDD (Ligand-Based Drug Design) - como base para desenvolvimento deste trabalho. Nesta estratégia, utiliza-se o conhecimento de moléculas (ligantes) e de suas atividades biológicas conhecidas previamente determinadas experimentalmente, como protótipos para a busca de novas entidades químicas com atividade biológica semelhante ou melhorada. Sendo assim, o presente trabalho teve como objetivo a síntese e avaliação biológica de moléculas bioativas para o tratamento de doenças parasitárias. Baseando-se no conhecimento prévio da atividade antiparasitária de compostos carbonílicos α,ß-insaturados e hidrazonas, foram sintetizados séries de compostos destas classes químicas na busca de novos agentes quimioterápicos. Os compostos obtidos foram avaliados contra a forma epimastigota de Trypanosoma cruzi, promastigota de Leishmania donovani, amastigota de Leishmania infantum e, também, determinou-se o seu grau de citotoxicidade (CC50) frente a células de macrófago humanos diferenciado (THP-1). As 31 moléculas obtidas foram caracterizadas por técnicas de ponto de fusão, RMN 1H e RMN 13C e avaliada sua pureza por HPLC. Os compostos da classe da cinamoil-hidrazonas apresentaram-se como promissores antiparasitários, mostrando atividade frente a forma promastigota (Leishmania donovani), 4 dos 12 compostos foram ativos (IC50= 1,27 - 13,68 µM) e frente a forma amastigota (Leishmania infantum), 10 dos 12 compostos apresentaram atividade (9,09 - 63,5 µM). Mesmo apresentando citotoxicidade moderada (CC50 = 8,83 - 87,47 µM), os compostos obtiveram valores inferiores ao fármaco de referência (doxorubicina: CC50 = 0,26 µM). Diante do exposto, o planejamento de fármacos realizado por LBDD mostrou-se bem-sucedido, pois a classe de cinamoil-hidrazonas mostrou-se promissora como antiparasitários, visto sua atividade na escala de baixo micromolar e moderada citotoxicidade em células humanas. Esses resultados assinalam que a classe de compostos descrita está passível a continuar sendo investigada no intuito de aprimorar os protótipos obtidos na busca de novos agentes quimioterápicos antiparasitários e desvendar os mecanismos de ação leishmanicida

Despite to the great medical and social relevance and the amount of deaths in underdeveloped and developing countries, neglected diseases (ND) still do not have an effective therapy. Among the various ND, illnesses such as Chagas disease, visceral leishmaniasis and malaria holds a great importance in the Brazilian scenario due to high incidence and social damage. The drugs available for the treatment of these parasitosis present high toxicity and, in some cases, resistance by the pathogens. Thus, the planning and development of new, safer and more effective chemotherapeutic substances are urgent needed. Among the different drug planning strategies, we selected ligand-based drug design (LBDD) as the basis for the development of this work. In this strategy, we use the knowledge of molecules (ligands) and their known biological activities previously determined experimentally, as prototypes to search for new chemical entities with similar or improved biological activity. Therefore, the present work aimed the synthesis and biological evaluation of bioactive molecules for the treatment of parasitic diseases. Based on previous knowledge of the antiparasitic activity of α,ß-unsaturated and hydrazone carbonyl compounds, series of compounds of these chemical classes were synthesized in search of new chemotherapeutic agents. The compounds obtained were evaluated against the epimastigote form of Trypanosoma cruzi, Leishmania donovani promastigote, Leishmania infantum amastigote and their cytotoxicity (CC50) against differentiated human macrophages (THP-1). The 31 molecules obtained were characterized by melting point, 1 H NMR and 13C NMR techniques and their purity were characterized by HPLC. The cinnamoyl hydrazone class compounds showed promising antiparasitic activity, showing activity against promastigote form (L. donovani), 4 of 12 compounds were active (IC50 = 1.27 - 13.68 µM) and amastigote form (L. infantum), 10 of the 12 compounds showed activity (9.09 - 63.5 µM). Even presenting moderate cytotoxicity (CC50 = 8.83 - 87.47 µM), the compounds had values below the reference drug (doxorubicin: CC50 = 0.26 µM). Considering the results, LBDD drug planning proved to be successful and the class of cinnamoyl hydrazones were promising as antiparasitics due to its activity in low micromolar scale and moderate cytotoxicity in human cells. These results indicate that the described class of compounds can be further investigated in order to improve the prototypes obtained in the search for new antiparasitic chemotherapeutic agents and to unravel the mechanisms of action of leishmanicidal molecules

Chalcones bearing N, O, and S-heterocycles: Recent notes on their biological significances

Because of its relatively easy synthesis, chalcone skeleton has been as a point of interest for organic and medicinalchemists from research groups worldwide. Chalcone scaffold constitutes the core of some interesting biologicallyactive natural products. Chalcone derivatives are among feasible potent active agents, such as anticancer, antibacterial,antifungal, antileishmanial, antimalarial, and antiviral. Due to the knowledge of heterocyclic chemistry, recentlychalcones bearing heterocyclic moieties have been synthesized and biologically investigated for specific target ofdiseases. The current review focuses on the latest application of chalcones integrated with N, O, and S-heterocyclicsystem and their wide spectrum of biological performance during 10 years (2010–2019). The results reported inthe review indicate that many chalcone-heterocycle hybrids may be useful as future drug candidates due to theircomparable or higher activity than that of the standards.

Synthesis and biological evaluation of new 2-(4-fluorophenyl) imidazol-5-ones as anticancer agents

Two series of imidazolones were designed, synthesized, and evaluated for their anticancer activity against four cancercell lines: Hela, MCF-7, PC3, and HCT-116, where four compounds 6, 25, 26, and 29 showed good potency againstthe whole panel. Compound 30 showed a cytotoxic effect against PC3 cell lines compared to that of the standarddoxorubicin with IC50 = 8.15µM, while compounds 4 and 18 showed moderate activity with IC50 range of 10.58–11.45µM. Enzyme inhibition assay was implemented against CDK2A and VEGFR-2; where varied activities were obtained.Compound 6 exhibited the highest inhibitory activity against VEGFR-2 with an IC50 value of 67 nM and moderateinhibition against CDK2A, while compound 26 achieved the best result against CDK2A with an IC50 value of 0.66 µM

Synthesis with spectral investigation of new ligand derived from pyrimidine with some metal complexes / 国际药学研究杂志

New ligand were synthesized by two steps in first steps were prepared chalcones compound from reacting of various carbonyl compounds (3-amino acetophenone with salicyldehyde,the second steps were closure of the ring by reacting(chalcones compound(AS) with thiouria, then reaction mixture was reflux for (8h) to produce Pyrimidine derivatives(AST) also prepared some complexes with Fe(II),Co(II), Ni(II),Cu(II),the ligand (AST)with its complexes were characterized by ((FT.IR, Uv-Vis, HNMR, Mass)–spectra,elemental analysis, melting point, molar conductivity).

Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active not only conferred cytoprotection of HO-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, exhibited higher cytoprotective and neuroprotective potential and Overall, our findings showed compound could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

Synthesis and physicochemical studies of vanillin chalcones / Síntesis y estudios fisicoquímicos de vainillin-chalconas

SUMMARY Some chalcone compounds are synthesized and their characterization was done by spectroscopic techniques such as IR, NMR and mass spectrometry. Some physicochemical properties such as acoustical properties, refractive index, conductance and partition coefficient have been studied for these synthesized compounds in N, N-dimethyl formamide and chloroform at 303.15 K. The studied properties are useful in QSAR studies and applications of these compounds in various other fields. It is observed that these parameters are affected by solvent and substitutions present in compounds.

RESUMEN Se sintetizaron algunos compuestos del tipo chalcona y su caracterizaron mediante técnicas espectroscópicas tales como IR, RMN y espectrometría de masa. Algunas propiedades fisicoquímicas tales como propiedades acústicas, índice de refracción, conductancia y coeficiente de reparto se estudiaron, para los compuestos sintetizados, en N,N-dimetil formamida y cloroformo a 303,15 K. Las propiedades estudiadas son útiles en estudios QSAR y en aplicaciones de estos compuestos en otros campos. Se observa que estos parámetros se ven afectados por el disolvente y las sustituciones presentes en los compuestos.

Structure-activity relationship of flavonoids and its application in pulmonary inflammatory diseases / 中草药

As polyphenolic compounds in nature, flavonoids are classified into flavones, flavanones, flavonols, flavanonols, isoflavones, isoflavanones, flavan-3-ols, anthocyanidins, and chalcones according to their chemical structures. In general, flavonoids with different structures always have different biological activities. Many studies have shown that flavonoids exhibit a wide range of pharmacological effects, such as anti-oxidant, antimutagenic, antitumor, anti-inflammatory, antibacterial, antiviral, and immunomodulatory activities. The anti-inflammatory and anti-oxidant properties of flavonoids make them likely to be candidates for prevention and treatment of pulmonary inflammatory diseases. Thus, this review focuses on the application of flavonoids in pulmonary inflammatory diseases, as well as establishes some structure-activity relationships between this biological potential and chemical profile of these compounds, which can provide the references for the development and utilization of flavonoids.

1-Octanol-water partition coefficient of some cyanopyridine and chalcone compounds / Coeficientes de reparto 1-octanol-agua de algunos compuestos derivados de cianopiridina y chalcona

SUMMARY The partition coefficients (P) of some synthesized cyanopyridine and chalcone compounds have been studied in 1-octanol-water system at different pH. It is observed that log P depends on pH and nature of substitution group present in the compounds. The central moiety also play important role to affect hydrophilic/ hydrophobic nature of compounds. There is no regular trend for the variation of log P with different pH.

RESUMEN Los coeficientes de reparto (P) de algunos compuestos sintetizados derivados de cianopiridina y chalcona se estudiaron en el sistema 1-octanol-agua a diferentes valores de pH. Se observa que log P depende del pH y de la naturaleza del grupo sustituyente presente en los compuestos. El grupo central también desempeña un papel importante en la naturaleza hidrofílica/hidrofóbica de los compuestos. No hay una tendencia regular para la variación de log P con el pH.

The reaction of cinnamaldehyde and cinnam(o)yl derivatives with thiols

Spurred by the alleged relevance of the thia-Michael reaction in the bioactivity of various classes of cinnam(o)yl natural products and by the development of a quick NMR assay to study this reaction, we have carried out a systematic study of the "native" reactivity of these compounds with dodecanethiol and cysteamine as models, respectively, of simple thiols and reactive protein thiols that can benefit from iminium ion catalysis in Michael reactions. Cinnamoyl esters and amides, as well as cinnamyl ketones and oximes, did not show any reactivity with the two probe thiols, while cinnamaldehyde () reacted with cysteamine to afford a mixture of a thiazoline derivative and compounds of multiple addition, and with aliphatic thiols to give a single bis-dithioacetal (). Chalchones and their vinylogous C5-curcuminoid derivatives were the only cinnamoyl derivatives that gave a thia-Michael reaction. From a mechanistic standpoint, loss of conjugation in the adduct might underlie the lack of a native Michael reactivity. This property is restored by the presence of another conjugating group on the carbonyl, as in chalcones and C5-curcuminoids. A critical mechanistic revision of the chemical and biomedical literature on cinnamaldehyde and related compounds seems therefore required.

Ultrasonic behavior of various chalcones in some solvents at different temperatures / Comportamiento ultrasónico de varias chalconas en algunos disolventes a diferentes temperaturas

Ultrasonic velocity, density and viscosity of some synthesized chalcones were measured in N,N-dimethyl formamide and chloroform at different temperatures (298.15 to 318.15 K). From these experimental data, various acoustical parameters such as specific impedance (Z), adiabatic compressibility (k s), Rao's molar sound function (Rm), intermolecular free path length (Lf), solvation number (Sn), internal pressure (Π) have been calculated in order to understand the molecular interactions in the studied solutions. The results are interpreted in terms of molecular interactions occurring in the solutions.

La velocidad ultrasónica, la densidad y la viscosidad de soluciones de algunas chalconas sintéticas se midieron en N, N-dimetilformamida y cloroformo a diferentes temperaturas (desde 298,15 hasta 318,15 K). A partir de estos datos experimentales, se calcularon diversos parámetros acústicos tales como la impedancia específica (Z), la compresibilidad adiabática (k s), la función de sonido molar de Rao (Rm), la longitud de trayecto libre intermolecular (Lf), el número de solvatación (Sn) y la presión interna (Π), para comprender las interacciones moleculares en las soluciones estudiadas. Los resultados se interpretan en términos de las posibles interacciones moleculares que ocurren en las soluciones.

Pyrimidinethione derivatives with tosyl substitution: Synthesis, and antimicrobial property investigation.

Substitution of tosyl group on hydroxyacetophenones orhydroxybenzaldehyde and their subsequent condensation yielded several tosyloxy substituted chalcones which were derivatized to obtain the corresponding pyrimidinethione derivatives. The synthesized compounds were characterized by spectroscopic techniques like FT-IR, 1H NMR, 13C NMR, and mass spectrometry. These compounds were subjected to initial screening for their bioactivity using zone of inhibition method and were found moderately active against the tested microorganisms, viz. Mycobacterium smegmatis, Staphylococcus aureus, Escherichia coli, and Candida albicans.

Synthesis and in vitro Anti Microbial Evaluation Including Anti-Malarial Activity of Pyrazole Based Novel Cinnoline Derivatives.

A Series of 4-methyl-3-[5-(substituted phenyl)-4, 5-dihydro-1H-Pyrazol-3-yl] Cinnoline-6-Sulfonamide were synthesized from 4-methyl-3-acetylcinnoline-6-Sulfonamido chalcones and hydrazines. The structure of the synthesized compounds were characterized by UV, IR, NMR & Mass spectral data, and evaluated for their in vitro anti-malarial and anti-bacterial activity to get new congeners as analogs of Pyrazole based Cinnoline compounds as a potent anti-Malarial and anti-microbial agents. All analogues exhibited in vitro anti-malarial activity against Plasmodium falciparum and all the analogues showed good anti-bacterial activity against various pathogenic microbes.

Biological activities of polyphenols from Polygonum lapathifolium / Actividades biológicas de polifenoles de Polygonum lapathifolium

Polygonum lapathifolium is an invasive plant spread worldwide, which has been used in traditional medicine for its biological activities. We studied chemical profile of the aerial part using HPLC/DAD/ESI-MS. Eight flavonoids, two chalcones and gallic acid were isolated, identified nad tested for their activity in seven experimental models (for antioxidant, alpha/beta-glucosidase inhibitory, antimicrobial, anticholineserase activity). Our results showed that P. lapathifolium is a valuable source of compounds with perspective biological activities...

Polygonum lapathifolium es una planta invasora cuya presencia se extiende por todo el mundo y que ha sido utilizada en la medicina tradicional por sus actividades biológicas. Analizamos el perfil químico de la parte superficial utilizando HPLC/DAD/ESI-MS. Ocho flavonoides, dos chalconas y ácido gálico fueron aislados, identificados y analizados en relación a sus actividades en siete modelos experimentales (de actividad antioxidante, alfa/beta-glucosidasa inhibitoria, antimicrobiana, anticholineserasa). Nuestros resultados demuestran que P. lapathifolium es una valiosa fuente de compuestos con actividades biológicas prometedoras...

Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus.

Background & objectives: Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics. Methods: Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method. Results: All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX. Interpretation & conclusions: oOur study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents.

Actividad inhibitoria de dihidroxifenil propenona sobre betalactamasas de Enterobacter cloacae: estudio preliminar en el desarrollo de fármacos para enfrentar la resistencia bacteriana / Inhibitory activity of dihydroxy-phenyl-propenone on betalactamase of Enterobacter cloacae : Preliminary study for drug development to overcome bacterial resistance

Introducción . Los microorganismos patógenos como Enterobacter cloacae producen betalactamasas que les confieren resistencia frente a los antibióticos betalactámicos; se ha identificado, además, la actividad limitada de los inhibidores enzimáticos, de modo que la única posibilidad de enfrentar la resistencia es el diseño de nuevos fármacos y su uso racional. Objetivo. Evaluar el efecto de la chalcona dihidroxifenil propenona sobre un aislamiento clínico de E. cloacae y sobre la betalactamasa aislada a partir de este microorganismo resistente como un aporte en la búsqueda de compuestos inhibidores de las betalactamasas. Materiales y métodos. Se sintetizó la chalcona dihidroxifenil propenona y se evaluó su efecto sobre el aislamiento clínico de E. cloacae para determinar la concentración inhibitoria mínima mediante el método de microdilución en caldo y con la betalactamasa purificada mediante cromatografía de afinidad se realizaron estudios espectrofotométricos de cinética enzimática. Resultados. La concentración inhibitoria mínima de la dihidroxifenil propenona sobre E. cloacae fue de 35 µg/ml; el porcentaje de recuperación de la betalactamasa a partir del microorganismo fue de 31,75 %; en el estudio cinético se evidenció actividad inhibitoria de acuerdo con los parámetros cinéticos de V max =1,7 x 10 -3 µM/minuto y K M´ =2330 µM. Conclusión. La chalcona dihidroxifenil propenona ejerce su actividad inhibitoria por medio de la interacción con la betalactamasa y, de esta manera, protege la integridad estructural de los antibióticos betalactámicos; dicho efecto sinérgico la convierte en un compuesto promisorio en la búsqueda de alternativas para enfrentar la resistencia bacteriana.

Introduction: Enterobacter cloacae is a pathogenic microorganism with the ability to produce betalactamase enzymes, which makes them resistant to betalactamic antibiotics. Additionally, the limited activity of enzymatic inhibitors has been identified, and, therefore, the design of new drugs and the promotion of their rational use are the only possibilities to overcome this problem. Objective: The aim of this research was to evaluate the effect of dihydroxy-phenyl-propenone on a clinical isolate of E. cloacae , as well as its activity on a betalactamase isolated from this resistant microorganism in order to contribute to the search for new betalactamase inhibitors. Materials and methods: Dihydroxy-phenyl-propenone chalcone was synthesized and evaluated on a clinical isolate of E. cloacae to determine the minimum inhibitory concentration by broth microdilution; once the betalactamase enzyme was purified by affinity chromatography, a spectrophotometric analysis was done to evaluate its kinetic activity. Results: The minimum inhibitory concentration value of dihydroxy-phenyl-propenone on E. cloacae was 35 µg/ml; the recovery percentage of the betalactamase from the microorganism was 31.75% and the kinetic parameters were V max =1.7 x 10 -3 µM/min and K M = 2330 µM, which show an important inhibitory activity. Conclusion: Dihydroxy-phenyl-propenone has shown inhibitory activity on betalactamase enzymes and the ability to protect the chemical integrity of betalactamic antibiotics; this synergistic effect turns it into a promising compound in the search for new alternatives to overcome bacterial resistance.

Newly-synthesized chalcones-inhibition of adherence and biofilm formation of methicillin-resistant Staphylococcus aureus

Biofilm formation and adherence of bacteria to host tissue are one of the most important virulence factors of methicillin-resistant strains of Staphylococcus aureus (MRSA). The number of resistant strains is seriously increasing during the past years and bacteria have become resistant, not only to methicillin, but also to other commonly used antistaphylococcal antibiotics. There is a great need for discovering a novel antimicrobial agent for the treatment of staphylococcal infections. One of the most promising groups of compounds appears to be chalcones. In present study we evaluated the in vitro effect of three newly synthesized chalcones: 1,3-Bis-(2-hydroxy-phenyl)-propenone, 3-(3Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone and 3-(4-Hydroxy-phenyl)-1-(2-hydroxyphenyl)-propenone on glycocalyx production, biofilm formation and adherence to human fibronectin of clinical isolates and laboratory control strain of MRSA (ATCC 43300). Subinhibitory concentrations of the tested compounds reduced the production of glycocalyx, biofilm formation and adherence to human fibronectin of all MRSA strains. Inhibition of biofilm formation was dose dependent and the most effective was 1,3-Bis-(2-hydroxy-phenyl)-propenone. In our study we demonstrated that three newly-synthesized chalcones exhibited significant effect on adherence and biofilm formation of MRSA strains. Chalcones may be considered as promising new antimicrobial agents that can be used for prevention of staphylococcal infections or as adjunct to antibiotics in conventional therapy.

Spectrophotometric Analysis of Bovine Serum Albumin in Presence of 1-(4-Methylphenyl)-3-Phenylprop-2-En-1-Ones.

A series of chalcones was synthesized by the Claisen-Schmidt condensation and the structures of 1- (4-methylphenyl)-3-phenylprop-2-en-1-ones were established with the help of IR and NMR study, then their effect was observed on bovine serum albumin. We have found that the synthesized chalcones interacted with bovine serum albumin and produce a great effect on their presence.