Abstract Cheese has become an important food item that may provide great nutritional benefits to consumers all over the world. Rennet is the most important milk coagulant obtained from calf stomach but nowadays due to lesser availability of ruminant stomach, higher rennet prices, religious concerns (Islamism; Halal / Haram) or the ban of recombinant calf rennet has given rise to the need for other substitutes than rennet. The present study was conducted to develop vegetative extracts of Citrus aurantium flowers, fig, pineapple, and melon extract as vegetative coagulants as an economical, easily available and halal source and their evaluation on basis of pH, dry matter protein content, milk clotting, and proteolytic activities potential in comparison with rennet and acid. The protein contents of CAFE, fig latex and bromelain were much greater than melon extract. The trend in milk clotting activity (MCA), proteolytic activity (PA) and MCA/PA ratio was rennet > acid > bromelain ˃ CAFE ˃ fig latex> melon extract. ORAC assay for antioxidant potential of extracts showed the following trend: fig latex 592 µM (TE)>CAFE 566 µM (TE)>bromelain 130 µM (TE)> melon extract 120 µM (TE) using Trolox as standard. These plant extracts proved a better substitute for animal rennet in the cheese industry.

Resumen Las plantas han desarrollado la base de los sistemas tradicionales de medicina que existen desde hace miles de años debido a la presencia de constituyentes bioactivos vitales. Además de las numerosas actividades antioxidantes, antimicrobianas, hipoglucemiantes, anticancerígenas y de los productos naturales, existe un reconocimiento limitado con respecto a los diversos atributos terapéuticos de las plantas medicinales como Momordica charantia, Syzygium cumini, Zingiber officinale y Parthenium hysterophorus. El estudio actual fue diseñado para explorar las capacidades inhibidoras de enzimas (alfa glucosidasa y acetilcolinesterasa) y citotóxicas de las fracciones solventes de estas plantas autóctonas. Todas las muestras tuvieron efectos inhibidores sobre la alfa glucosidasa, pero los fraccionamientos metanólicos de cada planta exhibieron una mayor eficacia inhibidora contra la acción enzimática en comparación con otros fraccionamientos. A excepción del extracto metanólico de Parthenium hysterophorus (33,25 ± 0,43), todas las demás plantas estudiadas, a saber. Zingiber officinale (50,33 ± 0,99), S. cumini (73,91 ± 1,05) y Momordica charantia (72,30 ± 1,17) indicaron más del 50 % de potenciales inhibidores de la alfa glucosidasa. Las inhibiciones de acetilcolinesterasa (porcentaje de inhibición) por diferentes fracciones de P. hysterophorus, Z. officinale, S. cumini y M. charantia estuvieron en el rango de 0,23 ± 0,14 a 11,40 ± 0,26, 13,04 ± 0,11 a 44,05 ± 0,76, 4,21 ± 0,15 a 71,55 ± 0,80 y 1,03 ± 0,09 a 50,12 ± 0,82 respectivamente. Entre todas las plantas estudiadas, Momordica charantia, Syzygium cumini y Zingiber officinale no fueron mutagénicas. Aunque se observó una ligera variación en las bioactividades, todos los extractos botánicos son excelentes fuentes de constituyentes bioactivos con el potencial de inhibir la alfa glucosidasa y la acetilcolinesterasa. Se justifica una mayor investigación a este respecto que involucre una evaluación guiada por bioensayo.

Abstract Plants have developed the foundation of traditional systems of medicine that have been in existence for thousands of years due to the presence of vital bioactive constitutes. Aside from antioxidant, antimicrobial, hypoglycemic, anticarcinogenic and numerous activities of natural products, limited recognition regarding diverse therapeutic attributes of medicinal plants such as Momordica charantia, Syzygium cumini, Zingiber officinale and Parthenium hysterophorus exist. The current study was designed to explore the enzyme inhibitory (alpha glucosidase and acetylcholinesterase) and cytotoxicity capacities of solvent fractions of these indigenous plants. All the samples had inhibitory effects on alpha glucosidase, but methanolic fractionations of each plant exhibited greater inhibitory efficacy against enzyme action compared to other fractionations. Except for the methanolic extract of Parthenium hysterophorus (33.25 ± 0.43), all other studied plants, viz. Zingiber officinale (50.33 ± 0.99), S. cumini (73.91 ± 1.05) and Momordica charantia (72.30 ± 1.17) indicated more than 50% alpha glucosidase inhibitory potentials. Acetylcholinesterase inhibitions (percentage inhibition) by different fractions of P. hysterophorus, Z. officinale, S. cumini and M. charantia were in the range of 0.23 ± 0.14 to 11.40 ± 0.26, 13.04 ± 0.11 to 44.05 ± 0.76, 4.21 ± 0.15 to 71.55 ± 0.80 and 1.03 ± 0.09 to 50.12 ± 0.82 respectively. Among all studied plants, Momordica charantia, Syzygium cumini, and Zingiber officinale were non-mutagenic. Although slight variation in bioactivities was observed, all the botanical extracts are excellent sources of bioactive constituents with the potential to inhibit alpha glucosidase and acetylcholinesterase. Further research in this regard is warranted involving bioassay-guided assessment.

Abstract The present study aimed to compare the crude, modified and hydrolyzed gums of Dalbergia sissoo and Acacia modesta as a biodegradable binder for drug delivery system using acetaminophen as a model drug. The physiochemical properties such as pH, fluorescence analysis and swelling index were determined. The gums were hydrolyzed and modified. Acetaminophen tablets were prepared using wet granulation technique and the gum solutions were used as a binder. Hydroxypropyl methylcellulose was used as a synthetic binder. Different properties of granules and tablets were evaluated. Results showed that both gums were acidic in nature, while D. sissoo and A. modesta showed light brown and creamy color in fluorescence analysis. The swelling ratio was the highest in water followed by 0.1N HCl and least in phosphate buffer. The prepared tablets showed faster and slower dissolution profiles in the same dissolution system. The crude gums have the highest dissolution rate, and this rate was decreased in the case of modified and hydrolyzed gums samples. The crude gums showing slower release can be useful in sustained-release tablets, while the modified gums having faster release rate are helpful in conventional tablet formulation. Taken together, the selected gums could be a good model for evaluation as a binder or hydrophilic polymer in tablet formulation.

Abstract The objective of the current investigation was to evaluate the okra before cooking (fresh) and after cooking to determine the best cooking method by using compositional analysis, colour, texture, sensory evaluation and pesticide residues reduction. The cooking methods used were steam blanching, simmering, baking and sautéing. Cooking treatments resulted in a momentous increase (p < 0.05) in crude fibre and fat content during sautéing and total carbohydrate in baking in comparison to control. The CIE lab coordinates (L* and b*) significantly decreased while a* increased in all cooking treatments except in baking. The texture analysis revealed a significant (p < 0.05) reduction in shear force N (Newton) due to contact of the heating medium in moist cooking i.e. steam blanching and simmering. Sautéing and steam blanching scored better and showed acceptance of the consumers except simmering that exhibited lower acceptability (p < 0.01). Moreover, among the analyzed pesticide residues, minimum reduction occurred in cypermethrin (8.57-37.14-%), while the chlorpyrifos was completely removed in case of baking and sautéing. Among all cooking treatments, only sautéing resulted in maximum pesticide residues reduction. The study revealed that the sautéing cooking treatment was best to preserve the vegetable nutrients compounds, maximum pesticide residues reduction and maybe among preferred cooking treatments.

Abstract Allium sativum (garlic), an aromatic bulbous plant is one of the most vital and oldest authenticated herbs which has been utilized from ancient times as a traditional medicine. A. sativum has cardioprotective, antimicrobial, anti-inflammatory, antidiabetic, antioxidant and anticancer properties due to a large range of phenolic compounds and sulfur containing compounds. The current study was conducted to assess the antioxidant chemistry, and numerous bioactivities of A. sativum bulbs extracts in different solvents. Ethanol fraction was the most active antioxidant and showed maximum total phenolic content (16.18 g GAE/100 g), total flavonoid content (95.04 g CE/100 g) and free radical scavenging activity (75.50 %). Methanol (4 %) fraction exhibited maximum antiglycation activity. Aqueous, n-hexane and ethyl acetate fractions exhibited maximal (52 %, 24 % and 38 %) inhibitions of alpha-amylase, alpha-glucosidase and acetylcholinesterase respectively. In an antimicrobial assay, ethanol (59.05 %) and chloroform (72.92 %) fractions showed maximum inhibition of Pasturella multocida and Staphylococcus aureus strains respectively. n-butanol and n-hexane fractions showed maximum (31 %) antihemolytic activity and (20 %) thrombolytic activities respectively. A. sativum bulb extracts and fractions have noteworthy bio-efficacies that holds promise to be used as a source of natural drug to cure various disorders.

Resumen Allium sativum (ajo), una planta bulbosa aromática, es una de las hierbas autenticadas más vitales y antiguas que se han utilizado desde la antigüedad como medicina tradicional. A. sativum tiene propiedades cardioprotectoras, antimicrobianas, anti-inflamatorias, anti-diabéticas, anti-oxidantes y anti-cancerígenas debido a una amplia gama de compuestos fenólicos y compuestos que contienen azufre. El estudio actual se llevó a cabo para evaluar la química antioxidante y numerosas bioactividades de extractos de rizoma de A. sativum en diferentes disolventes. La fracción de etanol tuvo la mayor actividad antioxidante y mostró un contenido fenólico total máximo (16.18 g GAE / 100 g), contenido total de flavonoides (95.04 g CE / 100 g) y actividad captadora de radicales libres (75.50 %). La fracción de metanol (4 %) exhibió la mayor actividad de antiglicación. Las fracciones acuosa, de n-hexano y de acetato de etilo inhibieron la actividad de alfa-amilasa, alfa-glucosidasa y acetilcolinesterasa, en 52 %, 24 % y 38 % respectivamente. En el ensayo antimicrobiano, las fracciones de etanol (59.05 %) y cloroformo (72.92 %) mostraron una inhibición máxima de las cepas de Pasturella multocida y Staphylococcus aureus, respectivamente. Las fracciones de n-butanol y n-hexano mostraron actividad anti-hemolítica (31 %) y trombolítica (20 %) respectivamente. Los extractos y fracciones de rizoma de A. sativum tienen bioeficacia notable con potencial de ser utilizadas como una fuente de fármaco natural para curar diversos trastornos.

Abstract A wide variety of cellular mechanisms such as cell division and metabolic processes are maintained by protein-protein interactions (PPIs). The identification of PPI through laboratory techniques is costly, time-consuming, difficult, and challenging. However, computational techniques were generated for PPIs prediction. In alfalfa (Madicago sativa), PPI was predicted among 12 MsMAPKs and 4 MsPP2Cs using a docking approach. For homology modelling, the Swiss model was employed while PROCHECK, ERRAT, and Verify3D were used to validate 3D models. The Ramachandran plots were obtained from PROCHECK which showed value more than 90% (nPP2C1, PP2C1, PP2C, and MSK-3 revealed 92.9%, 94.2%, 92.4%, and 91.1% respectively) for high-quality structures. The HawkDock server and the BIPSPI server were used to analyse protein docking and predict interaction sites, respectively. Our findings demonstrated that MsPP2C docking sites play an important role in the identification and docking of MsMAPKs. The binding free energy ranged from -0.16Kcal/mol to -49.15Kcal/mol for all MsMAPKs and MsPP2Cs, indicating that they interact. Docking site analysis showed that there were 48 pairs of PPIs which indicated that MsPP2Cs can perform a vital role in other signaling pathways. This study found that all MsPP2Cs have docking sites for MsMAPKs, indicating that this method can accurately determine protein-protein interactions.

Abstract The bacterial species employ various types of molecular communication systems recognized as quorum sensing for the synchronization of differential gene expression to regulate virulence traits and biofilm formation. A variety of quorum sensing inhibitors; molecules that interfere with quorum sensing among bacteria have been examined which can block the action of autoinducers. Moreover, the studies have scrutinized various enzymes for their quorum quenching activity resulting in the degradation of signaling molecules or blocking of gene expression. So far, the studies have found that these approaches are not only capable to reduce the pathogenicity and biofilm formation but also resulted in increased bacterial susceptibility to antibiotics and bacteriophages. The effectiveness of these strategies has been validated in different animal models and it seems that these practices will be transformed in near future to develop the medical devices including catheters, implants, and dressings for the prevention of bacterial infections. Although many of these approaches are still in the research stage, the increasing library of quorum quenching molecules and enzymes will open innovative perspectives for the development of antibacterial approaches which will extend the therapeutic arsenal against the pathogenic bacterial species.

ABSTRACT The present study was conducted to evaluate five pre-characterized lead tolerant plant growth promoting rhizobacteria: Pseudomonas gessardii strain BLP141 (S2), Pseudomonas fluorescens A50 (S5), Pseudomonas syringae pv. syringae B728a (S6), Pseudomonas stutzeri strain 28a24 (S8) and Pseudomonas fluorescens strain LMG 2189 (S10), for their plant growth promotion, phytoremediation potential and physiological response on Helianthus annuus L. as test crop, exposed to different lead concentrations (300, 600 and 900 mg/kg). Crop was harvested after 30 days of sowing and data regarding growth parameters (root shoot length, root shoot fresh and dry weights), physiological attributes (photosynthetic rate, transpiration rate and substomatal CO2), and lead content in root and shoot of sunflower, were recorded. Results revealed that lead contamination decreased the growth and physiological attributes of plants at all levels of lead stress; however inoculation with lead tolerant rhizobacteria reversed the toxic effect of lead on the plants and improved the growth and physiological attributes of sunflower in lead contamination, as compared to plants grown in the un-inoculated lead contaminated treatments. Among the five isolates, S2, S5 and S10 promoted more growth, improving the physiological attributes and phytoremediation potential of plants at all levels of contamination as compared to plants grown in lead stress without inoculation.

RESUMEN Se evaluaron cinco rizobacterias promotoras del crecimiento tolerantes al plomo precaracterizadas: Pseudomonas gessardii cepa BLP141 (S2), Pseudomonas fluorescens A50 (S5), Pseudomonas syringae pv. syringae B728a (S6), Pseudomonas stutzeri cepa 28a24 (S8) y Pseudomonas fluorescens cepa LMG 2189 (S10), con relación a su efecto en el crecimiento, potencial de fitorremediación y respuesta fisiológica en Helianthus annuus L. como cultivo de ensayo expuesto a diferentes concentraciones de plomo (300, 600 y 900 mg/kg). El cultivo se cosechó después de 30 días de sembrado y se registraron los datos referentes a parámetros de crecmiento (longitud del brote y la raíz, peso fresco y seco del brote y la raíz), atributos fisiológicos (tasa fotosintética y de transpiración, CO2 estomático) y contenido de plomo en raíces y brotes de girasol. Los resultados indican que la contaminación por plomo mermó tanto el desarrollo como los atributos fisiológicos de las plantas en todos los niveles de agresión por plomo; sin embargo, la inoculación con rizobacterias tolerantes al plomo revirtió los efectos tóxicos y mejoró tanto el crecimiento como los atributos fisiológicos del girasol contaminado por este metal, en comparación con plantas cultivadas sin este tratamiento. De las cinco cepas aisladas, S2, S5 y S10 promovieron mayor crecimiento y mejoraron en mayor medida los atributos fisiológicos y el potencial de fitorremediación de las plantas en todos los niveles de contaminación en comparación de plantas cultivadas en un ambiente de agresión por plomo sin inoculación.

ABSTRACT Atmospheric pollution has emerged as a disaster in developing countries like Pakistan. The aim of this study was to observe and analyze the air quality status of the twin cities of Pakistan, Rawalpindi and Islamabad, with a combined population of 15 million. The concentration of criteria pollutants along with CO2 was measured at five different locations within these cities. Sampling was done for 24 h at each location using a mobile air quality monitoring lab. The overall concentrations of SO2, NOx and O3 were found to be within the permissible limits of the US-EPA standards and the National Environmental Quality Standards of Pakistan, with higher PM10 and CO2 concentrations at most locations. The highest concentrations of PM10 were observed at Saddar, Rawalpindi (184 µg m-3), while minimum values were observed at the Blue Area of Islamabad (121 µg m-3). The concentration of CO2 during the study period was found to be high in almost all locations, with Saddar, Rawalpindi, indicating the highest value (409 ppm). The concentrations of CO2 at the Blue Area and the National University of Science and Technology of Islamabad were observed to be as high as 385.3 and 246 ppm, respectively. The behavior of pollutants with different meteorological parameters was also studied. For source identification, backward air trajectories were also generated using the HYSPLIT model.

RESUMEN La contaminación atmosférica se ha perfilado como un desastre en países en desarrollo como Pakistán. El objetivo el presente estudio fue observar y analizar el estado de la calidad del aire en las ciudades paquistaníes gemelas de Rawalpindi e Islamabad, cuya población combinada es de 15 millones de habitantes. Se midieron las concentraciones de los principales contaminantes junto con las de CO2 en cinco sitios dentro de esas ciudades. El muestreo se realizó durante 24 h en cada sitio, utilizando un laboratorio móvil para medir la calidad del aire. Se encontraron concentraciones totales de SO2, NOx y O3 dentro de los límites permitidos de acuerdo con los estándares de la Agencia de Protección Ambiental de EUA y los Estándares Nacionales de Calidad Ambiental de Pakistán. Las concentraciones más altas de PM10 se observaron en Saddar, Rawalpindi (184 µg m-3), en tanto que los valores mínimos se obtuvieron en la Zona Azul de Islamabad (121 µg m-3). Durante el periodo de estudio, las concentraciones de CO2 permanecieron altas en casi todos los sitios, con un valor máximo de 409 ppm. En la Zona Azul y la Universidad Nacional de Ciencia y Tecnología de Islamabad se observaron concentraciones de CO2 de hasta 385.3 y 246 ppm, respectivamente. También se estudió el comportamiento de los contaminantes con diferentes parámetros meteorológicos. Para identificar las fuentes se utilizaron trayectorias inversas generadas con el modelo HYSPLIT.

Abstract This study was aimed to investigate the effect of bio-organic phosphate either alone or in combination with phosphorus solubilizing bacteria strain (Bacillus MWT-14) on the growth and productivity of two wheat cultivars (Galaxy-2013 and Punjab-2011) along with recommended (150–100 NP kg ha−1) and half dose (75–50 NP kg ha−1) of fertilizers. The combined application of bio-organic phosphate and the phosphorous solubilizing bacteria strain at either fertilizer level significantly improved the growth, yield parameters and productivity of both wheat cultivars compared to non-inoculated control treatments. The cultivar Punjab-2011 produced the higher chlorophyll contents, crop growth rate, and the straw yield at half dose of NP fertilizer; while Galaxy-2013, with the combined application of bio-organic phosphate and phosphorous solubilizing bacteria under recommended NP fertilizer dose. Combined over both NP fertilizer levels, the combined use of bio-organic phosphate and phosphorous solubilizing bacteria enhanced the grain yield of cultivar Galaxy-2013 by 54.3% and that of cultivar Punjab-2011 by 83.3%. The combined application of bio-organic phosphate and phosphorous solubilizing bacteria also increased the population of phosphorous solubilizing bacteria, the soil organic matter and phosphorous contents in the soil. In conclusion, the combined application of bio-organic phosphate and phosphorous solubilizing bacteria offers an eco-friendly option to harvest the better wheat yield with low fertilizer input under arid climate.

Abstract In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 μM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 μM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents.

Aluminum/carbon nanotube composite is a promising candidate material for aerospace applications owing to its high strength-to-weight ratio. Because of the low density of carbon nanotubes (CNTs), their dispersion is difficult in molten metal. We investigated induction melting, a fairly distinct approach to facilitate the dispersion of CNTs in molten aluminum. The nanocomposites were characterized using scanning electron microscopy, X-ray diffraction, transmission electron microscopy and mechanical testing. Refinement in crystallite size (∼320 nm) and increase in lattice strain (∼3.24 × 10−3) were observed in the composites. A simultaneous increase in yield strength (∼77%), tensile strength (∼52%), ductility (∼44%) and hardness (∼45%) was observed. Induction melting appeared to be a potential method to fabricate aluminum-CNTs composites.

Abstract: Introduction: The drug resistant Acinetobacter strains are important causes of nosocomial infections that are difficult to control and treat. This study aimed to determine the antimicrobial susceptibility patterns of Acinetobacter strains isolated from different clinical specimens obtained from patients belonging to different age groups. METHODS: In total, 716 non-duplicate Acinetobacter isolates were collected from the infected patients admitted to tertiary-care hospitals at Lahore, Pakistan, over a period of 28 months. The Acinetobacter isolates were identified using API 20E, and antimicrobial susceptibility testing was performed and interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The isolation rate of Acinetobacter was high from the respiratory specimens, followed by wound samples. Antibiotic susceptibility analyses of the isolates revealed that the resistance to cefotaxime and ceftazidime was the most common, in 710 (99.2%) specimens each, followed by the resistance to gentamicin in 670 (93.6%) isolates, and to imipenem in 651 (90.9%) isolates. However, almost all isolates were susceptible to tigecycline, colistin, and polymyxin B. CONCLUSIONS: The present study showed the alarming trends of resistance of Acinetobacter strains isolated from clinical specimens to the various classes of antimicrobials. The improvement of microbiological techniques for earlier and more accurate identification of bacteria is necessary for the selection of appropriate treatments.

resumo Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il)acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS2 e KOH alcoólico produziu 5-(1H-indol-3-il- metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a- w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase, e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados.

abstract A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.

Na pesquisa presente o fármaco esteróide antiasmático dipropionato de beclometasona foi submetido à biotransformação microbiana pelo Aspergillus niger. O dipropionato de beclometasona foi transformado, pela primeira vez, em metabólitos variados por biotransformação microbiana. Novos metabólitos do fármaco produzidos podem agir como novas moléculas potenciais e podem substituir os fármacos antigos em questão de segurança, eficácia e mínima resistência. Eles foram purificados por cromatografia em camada delgada preparativa e as suas estruturas foram elucidadas usando técnicas espectroscópicas modernas, como 13C NMR, 1H NMR; HMQC; HMQC; COSY, NOESY e espectrometria de massas, por exemplo, EI-MS. Purificaram-se quatro metabólitos, denominados (i) 17-monopropionato de beclometasona; (ii) 21-monopropionato de beclometasona: (iii) beclometasona e (iv) 21-propionato de 9beta,11beta-epoxi-17,21-diidroxi-16beta-metilpregna-1,4-dieno-3,20-diona.

In the present research, the steroidal anti-asthmatic drug beclomethasone dipropionate was subjected to microbial biotransformation by Aspergillus niger. Beclomethasone dipropionate was transformed into various metabolites first time from microbial transformation. New drug metabolites produced can act as new potential drug molecules and can replace the old drugs in terms of safety, efficacy, and least resistance. They were purified by preparative thin layer chromatography technique, and their structures were elucidated using modern spectroscopic techniques, such as 13C NMR, 1H NMR, HMQC, HMQC, COSY, and NOESY, and mass spectrometry, such as EI-MS. Four metabolites were purified: (i) beclomethasone 17-monopropionate, (ii) beclomethasone 21-monopropionate, (iii) beclomethasone, and (iv) 9beta,11beta-epoxy-17,21-dihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-propionate.