Synthesis of ciprofloxacin-linked 1,2,3-triazole conjugates as potent antibacterial agents using click chemistry: exploring their function as DNA gyrase inhibitors via in silico- and in vitro-based studies.

The antibacterial efficacy of some newly developed C-3 carboxylic group-containing ciprofloxacin-linked 1,2,3-triazole conjugates was studied. Twenty-one compounds from three different series of triazoles were synthesized using click chemistry and evaluated for their antibacterial activity against nine different pathogenic strains, including three Gram-positive strains, i.e. Enterococcus faecalis (ATCC29212), Staphylococcus aureus (ATCC25923), Staphylococcus epidermidis (clinical isolate), and six Gram-negative bacterial strains, i.e. Escherichia coli (ATCC25922), Pseudomonas aeruginosa (ATCC27853), Salmonella typhi (clinical isolate), Proteus mirabilis (clinical isolate), Acinetobacter baumannii (clinical isolate) and Klebsiella pneumonia (clinical isolate). Among the compounds, 10, 10a, 10b, 10c, 10d, 11a, 11f, 12c, 12e and 12f showed excellent activity with MIC values upto 12.5 µg mL-1, whereas the control ciprofloxacin showed MIC values of 0.781-25 µg mL-1 towards various strains. In addition, the low toxicity profile of the synthesized molecules revealed that they are potent antibiotics. Molecular docking and MD analysis were performed using the protein structure of E. coli DNA gyrase B, which was further corroborated with an in vitro assay to evaluate the inhibition of DNA gyrase. The analysis revealed that compound 10b was the most potent inhibitor of DNA gyrase compared to ciprofloxacin, which was employed as the positive control. Furthermore, the structure of two title compounds (11a and 12d) was characterized using single-crystal analysis.

Quantitative structure-activity relationship(QSAR) models for color and COD removal for some dyes subjected to electrochemical oxidation.

Electrochemical oxidation is an efficient method for the destruction of dyes in wastewater streams. The experimental conditions during electrochemical oxidation (EO) and molecular structure of a dye greatly influence the extent of degradation. The extent of degradation for a variety of dyes by EO can be predicted conveniently by the use of Quantitative structure-activity Relationship (QSAR) models. An abundant amount of published data on dye degradation by EO using highly variable experimental conditions lies unutilized to prepare QSAR models. In this study, an effort is made to use published experimental data on EO of aqueous dyes after applying an easy method of normalization, to prepare QSAR models for percent color and COD removal. Normalized color and COD removal were obtained by multiplying the reported removal by volume of reactor and concentration of dye; and divided by total current passed and the time of electrolysis. More than 15 molecular descriptors were computed using Schrodinger-suit 2018-3. The multiple linear regression (MLR) approach was used to develop normalized color and COD removal models. The quantum chemical descriptors: highest occupied molecular orbital energy (HOMO) and lowest unoccupied molecular orbital energy (LUMO), polar surface area (PSA), hydrogen bond donor count (HBD), and number of atoms were found significant. The statistical indices: goodness-of-fit, R2 > 0.75, and internal and external validations, Q2LOOCV and Q2ext, > 0.5, satisfied the criteria for predictive models and indicated that the method of normalization used in this study is adequate. Developed QSAR models are quite simple, interpretable, and transparent.

Ciprofloxacin-Tethered 1,2,3-Triazole Conjugates: New Quinolone Family Compounds to Upgrade Our Antiquated Approach against Bacterial Infections.

A newer ciprofloxacin series containing 1,2,3-triazole conjugates of ciprofloxacin was designed, synthesized, and well characterized using modern analytical techniques by reacting diversified anilines with ciprofloxacin obtained from ciprofloxacin hydrochloride. The newer conjugates were evaluated for their antimicrobial activity against various strains, viz. Staphylococcus aureus (ATCC25923), Enterococcus faecalis (clinical isolate), Staphylococcus epidermidis (ATCC3594), Escherichia coli (ATCC25922), Pseudomonas aeruginosa (ATCC27853), Salmonella typhi (clinical isolate), Salmonella typhimurium (clinical isolate), Acinetobacter baumannii (ATCC19606), Aeromonas hydrophila (ATCC7966), Plesiomonas shigelloides (ATCC14029), and Sphingo biumpaucimobilis (MTCC6362) in vitro. Interestingly, some of the conjugates showed superior antimicrobial activity as compared to the control drug ciprofloxacin. The three compounds 4i, 4j, and 4n showed strong activity with minimum inhibitory concentration (MIC) 0.78 µM, while the compound 4g showed MIC 1.56 µM against S. typhi (clinical). The compound 4a showed good efficacy against S. aureus (ATCC25923) and S. typhi (clinical) with MIC 3.12 µM, while the compound 4b exhibited efficacy with MIC 3.12 µM against S. aureus (ATCC25923) and the control drug ciprofloxacin showed MIC 6.25 µM. Among all of the synthesized compounds, 4e, 4f, 4g, 4h, 4p, 4q, 4t, and 4u displayed less than 20% hemolysis, while the rest of the compounds showed hemolysis in the range of 21-48%. Moreover, the structure of compound 4b was also established by single-crystal X-ray diffraction studies.

Challenges and Recent Advances of Novel Chemical Inhibitors in Medulloblastoma Therapy.

Medulloblastoma is a common term used for the juvenile malignant brain tumor, and its treatment is exciting due to different genetic origins, improper transportation of drug across the blood-brain barrier, and chemo-resistance with various side effects. Currently, medulloblastoma divided into four significant subsections (Wnt, Shh, Group 3, and Group 4) is based on their hereditary modulation and histopathological advancement. In this chapter, we tried to combine several novel chemical therapeutic agents active toward medulloblastoma therapy. All these compounds have potent activity to inhibit the medulloblastoma.

Homogeneous photocatalytic degradation of azo dye Reactive Black 5 using Fe(III) ions under visible light.

Efficient and cost-effective method to destroy complex dyes is warranted to combat increasing water pollution. In the present study, homogeneous photocatalytic oxidation (PCO) of Reactive Black 5 (RB5) dye was studied using ferric ions (Fe(III)) under visible light (VL) irradiation and sunlight (SL). In the presence of 5 mM ferric ions and at pH 2.6, more than 80% of initial 20 mg/L RB5 was decolourized in 60 min under artificial VL. Decolourization followed pseudo first-order kinetics with the reaction rate constant 0.0356 min-1. 79% of initial COD was removed at the end of 60 min, suggesting mineralization of RB5 as the main cause of decolourization. Using similar experimental conditions under SL, more than 90% RB5 was decolourized in 15 min with an almost 10-fold increase in the reaction rate constant (0.34 min-1). Rate and extent of RB5 destruction significantly decreased in the presence of •OH scavenger indicating photoreduction of Fe-hydroxo species and generation of •OH as the main mechanism of RB5 degradation. RB5 removal increased from ca. 30% to 84% with the increase in Fe(III) concentration from 0.5 to 5 mM. The corresponding 1st-order rate constants increased linearly from 0.006 to 0.036 min-1. RB5 degradation decreased linearly (R2 = 0.98) from 91.7% to 63.3% with the increase in initial RB5 concentration from 10 to 40 mg/L. Fe(III) induced homogenous PCO appears to be a reliable and low-cost method of advanced oxidation without the need for costly reagent such as H2O2.

Moving bed biofilm reactor developed with special microbial seed for denitrification of high nitrate containing wastewater.

Biological denitrification is the most promising alternative approach for the removal of nitrate from wastewater. MBBR inoculated with activated sludge is a widely studied approach, but very few studies have focused on the bioaugmentation of biofilm forming bacteria in MBBR. Our study revealed that the use of special microbial seed of biofilm forming denitrifying bacteria Diaphorobacter sp. R4, Pannonibacter sp. V5, Thauera sp. V9, Pseudomonas sp.V11, and Thauera sp.V14 to form biofilm on carriers enhanced nitrate removal performance of developed MBBR. Various process parameters C/N ratio 0.3, HRT 3 h at Nitrate loading 2400 mg L-1, Filling ratio 20%, operated with Pall ring carrier were optimized to achieve highest nitrate removal. After 300 days of continuous operation results of whole genome metagenomic studies showed that Thauera spp. were the most dominant and key contributor to the denitrification of nitrate containing wastewater and the reactor was totally conditioned for denitrification. Overall, findings suggest that bench-scale MBBR developed with biofilm forming denitrifying microbial seed accelerated the denitrification process; therefore in conclusion it is suggested as one of the best suitable and effective approach for removal of nitrate from wastewater.

Significant improvement in biodegradability of a real Optical Brightening Agent (OBA) wastewater using small doses of Fenton's reagent.

Optical Brightening Agent (OBA) wastewater (OBAW) has been reported to be highly resistant to biodegradation. In this study, a real OBAW from an industry which was already treated using primary and secondary treatments (residual COD of secondary clarifier overflow (SCO): 3400-3700 mgL-1) was further treated by Fenton's treatment (FT). Zahn-Wellens biodegradability test revealed that using small doses of H2O2 and Fe+2, the biodegradability of SCO improved to 90% as compared to ∼18% without FT. UV-Vis analysis revealed that ca. 80% of initially present OBAs were removed by treatment sequence outlined in this study. Biodegradability study on individual raw wastewaters from four types of OBAs (designated OBA-TS, OBA-DS-U, OBA-HS, and OBA-DS-D) being manufactured at the time of this study, revealed that OBA-TS wastewater was the most biodegradable (>95% biodegradability) followed by OBA-DS-U (∼60%), OBA-HS (∼20%), and OBA-DS-D (<5%). Application of FT improved the biodegradability of these streams as: OBA-DS-U (∼70%), OBA-HS (∼60%), and OBA-DS-D (∼50%). A treatment sequence consisting of waste coal dust (WCD) pretreatment-FT-biodegradation is a novel, economical, and sustainable approach to treating highly recalcitrant OBA wastewater.

Electrocoagulation treatment of simulated floor-wash containing Reactive Black 5 using iron sacrificial anode.

Floor-wash from dye finishing plant is a major source of color and wastewater volume for dyes industries. Batch electrocoagulation (EC) of simulated floor-wash containing Reactive Black 5 (RB5) was studied as a possible pretreatment option. More than 90% of initial 25mg/L of RB5 was removed at current densities of 4.5, 6, and 7.5 mA/cm(2) in the presence of Na(2)SO(4) and NaCl as supporting electrolytes; in less than one hour. Identical k(obs) (pseudo first-order reaction rate constant) values were obtained at initial pH of 3.74 for both electrolytes. However, at initial pH of 6.6, k(obs) values decreased in the presence of Na(2)SO(4) and remained same for NaCl as compared to that at pH 3.74. Highest extent of decolorization and k(obs) values were obtained at initial pH 9.0 for both electrolytes. Under identical conditions, specific energy consumption (SEC) was almost half in the presence of NaCl (~29 kWh/kg RB5) than that of Na(2)SO(4). Vinyl sulfone (VS) was detected as one of the products of EC indicating reduction of azo bonds as a preliminary step of decolorization. Mechanism of decolorization with respect to various experimental conditions was delineated. Generation and accumulation of VS was dependent on initial pH and type of electrolyte. Results of this study revealed that EC in the presence of sodium chloride can be efficiently used as a primary treatment for decolorization of floor-wash containing RB5.

Chitosan microspheres of aceclofenac: in vitro and in vivo evaluation.

The objective of this investigation was to achieve controlled drug release of Aceclofenac (ACE) microspheres and to minimize local side-effects in the gastrointestinal tract (GIT). Sustained release chitosan microspheres containing ACE were prepared using double-emulsion solvent evaporation method (O/W/O). Chitosan microspheres were prepared by varying drug to polymer ratio (1:3, 1:4, 1:5 and 1:6). Microspheres were characterized for morphology, swelling behavior, mucoadhesive properties, FTIR and DSC study, drug loading efficiency, in vitro release, release kinetics, and in vivo study was performed on rat model. ACE-loaded microspheres were successfully prepared having production yield, 57-70% w/w. Drug encapsulation efficiency was ranging from 53-72% w/w, Scanning electron microscopy (SEM) revealed particle size of microspheres was between 39 and 55 mum. FTIR spectra and DSC thermograms demonstrated no interaction between drug and polymer. The in vitro release profiles of drug from chitosan microspheres showed sustained-release pattern of the drug in phosphate buffer, pH 6.8. In vitro release data showed correlation (r2 > 0.98), good fit with Higuchi/Korsmeyer-Peppas models, and exhibited Fickian diffusion. ACE microspheres demonstrated controlled delivery of aceclofenac and apparently, no G.I.T. erosion was noticed.

Preparation and characterization of spray-dried mucoadhesive microspheres of aceclofenac.

OBJECTIVE: Microencapsulation of the anti-inflammatory drug aceclofenac (ACE) was investigated as a means of controlling drug release and minimizing or eliminating local side effects. METHOD: Microspheres were prepared by a spray-drying technique using solutions of ACE and three polymers, namely, carbopol, chitosan, and polycarbophil, in different weight ratios. RESULTS: The spray-dried mucoadhesive microspheres were characterized in terms of shape (scanning electron microscope), size (6.60-8.40 mum), production yield (34.10-55.62%), and encapsulation efficiency (58.14-90.57%). In vitro release studies were performed in phosphate buffer (pH 6.8) up to 10 hours. The spray-drying process of solutions of ACE with polymeric blends can give prolonged drug release. The in vitro release data were well fit into Higuchi and Korsmeyer-Peppas model and followed Fickian diffusion mechanism. In vivo data showed that the administration of ACE in polymeric microspheres prevented the gastric side effects. CONCLUSION: The formulations here described can be proposed for the oral administration of nonsteroidal anti-inflammatory drugs with minimal side effects on gastric mucosa.

Effects of solvent, pH, salts and resin fatty acids on the dechlorination of pentachlorophenol using magnesium-silver and magnesium-palladium bimetallic systems.

The effects of pH, organic co-solvent, salts such as sodium chloride, sodium sulfate, and co-pollutants, resin and fatty acids (RFAs) on the dechlorination of pentachlorophenol (PCP) by magnesium/silver (Mg/Ag) and magnesium/palladium (Mg/Pd) systems were examined in the present investigations. Such studies provide relevant information about the applicability of bimetallic systems for remediation of raw wastewaters (such as pulp bleaching effluents) or groundwater. Removal efficiencies of 10 mg L(-1) PCP by Mg/Pd and Mg/Ag systems at the end of 1 h reaction were 93% and 78%, respectively, in the presence of acetone (1% v/v). On the other hand, the removal efficiencies were 86% and 70% for reactions conducted in alcoholic solvents (1% v/v) using Mg/Pd and Mg/Ag systems, respectively. The efficiencies of PCP removal by the two bimetallic systems could be correlated to the dipole moments of co-solvents used. The second order reaction rate constant for PCP removal by Mg/Ag system was highest (0.03 L mg(-1) min(-1)) in the absence of any pH-control mechanism. Optimum pH for the dechlorination of PCP by Mg/Pd system was found to be approximately 5.5 and >92% of the compound was removed within 15 min of reaction. Presence of chlorinated and non-chlorinated resin fatty acids (RFAs) resulted in substantial reduction in the rate and extent of PCP removal by Mg/Ag system whereas dechlorination by Mg/Pd remained unaffected. Presence of sodium sulfate or sodium chloride in the reaction phase reduced the rate and extent of PCP removal by Mg/Ag system. PCP dechlorination by Mg/Pd system was adversely impacted by the addition of sodium chloride and unaffected by the presence of sodium sulfate.

Complete dechlorination of pentachlorophenol using palladized bacterial cellulose in a rotating catalyst contact reactor.

A rotating catalyst contact reactor (RCCR) was developed which consisted of palladized bacterial cellulose immobilized on acrylic discs for hydrodechlorination of pentachlorophenol (PCP). More than 99% of 40 mg L(-1) PCP was dechlorinated to phenol in the presence of hydrogen in batch mode at initial pH values of 5.5 and 6.5 within 2 h of reaction with stoichiometric release of free chloride. The rate of PCP dechlorination was found to be independent of rotational speed of discs. PCP (40 mg L(-1)) hydrodechlorination experiments were also conducted using RCCR in continuous flow mode at hydraulic retention times of 1 and 2 h. The average outlet PCP concentrations revealed that liquid phase in RCCR closely resembled that of a continuous flow complete mix reactor (CFMR). Approximately 12 and 11 L of 40 mg L(-1) PCP (pH 6.5) could be treated in RCCR with 99 and 80% efficiencies in batch and continuous flow modes, respectively without any appreciable loss of the catalytic activity. These results suggested reusability of palladized bacterial cellulose which in turn is expected to substantially reduce the cost of treatment process. Thus RCCR seems to have high potential for treatment of ground water contaminated with chlorinated organic compounds. Dried palladized bacterial cellulose has been used as a material for electrodes in a fuel cell. However, its application as a hydrodechlorination catalyst in a reactor operating under room temperature and atmospheric pressure has not been reported to the best of our knowledge. Scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction analyses suggested the irreversible deposition of palladium (Pd 0) particles on the bacterial cellulose fibrils.

Dechlorination of chlorophenols using magnesium-palladium bimetallic system.

Ninety-four percent removal of 10 mg L(-1) of pentachlorophenol (PCP) was achieved by treatment with 154.5mM Mg(0) and 0.063 mM K(2)PdCl(6) in the presence of 175 mM acetic acid in 1h reaction time. Dechlorination of PCP was found to be sequential and phenol was identified as the end product along with accumulation of trace concentrations of tetra- and trichlorophenols. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that palladium in its metallic form (Pd(0)) produced by reduction of Pd4+, was spatially separated from magnesium granules when acid was included in the reaction. These colloidal palladium particles generated active reductive species of hydrogen and dechlorinated chlorophenols. In the absence of acid, the efficiency of dechlorination of PCP by Pd/Mg(0) system was very low and chief mechanism of removal of the compound was through sorption onto solid surfaces. Thus, it was important to include acid in the system to: (a) facilitate corrosion of Mg(0) and reduction of Pd4+ to Pd(0), (b) provision of protons to produce H2, (c) retard formation of insoluble oxides and hydroxides that may deposit on the magnesium granules and sorb PCP and its partially dechlorinated products and. Application of 154.5 mM Mg(0)/0.063 mM K(2)PdCl(6) on PCP, 2,4,5-trichlorophenol (TCP) and 2-chlorophenol (MCP) with organic chloride equivalence showed that the rate and extent of removal increased with decrease in number of chlorine atoms on phenol.

Dechlorination of chlorophenols by magnesium-silver bimetallic system.

More than 85% of 10 mg L(-1) of pentachlorophenol (PCP) was removed by magnesium/silver (206/1.47 mM) bimetal system in the presence of acetic acid. Dechlorination was found to be sequential and phenol was identified as the ultimate hydrocarbon skeleton along with some accumulation of tetra-, tri-, and dichlorophenols. The dechlorination reaction was found to follow second-order kinetics. Lower PCP removal efficiency (35%) was observed when the reaction was carried out in the absence of acid using Mg(0)/Ag system. When the reaction was conducted using Mg(0) alone in the presence of acid, substantial sorption of PCP occurred with very low efficiency of PCP dechlorination. Dechlorination studies on 10 mg L(-1) initial concentrations of 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP) and 2,4,5-trichlorophenol (2,4,5-TCP), under identical conditions as to PCP, revealed that dechlorination efficiency and reaction rate constants decrease with decreasing number of chlorine atoms on the target compound. A correlation (R(2)>0.9) between the dechlorination rate constants and E(LUMO) for chlorophenols was obtained.