Insights on the structural characteristics and molecular dynamic studies of methyl vanillin Schiff base bio-compounds.

A new crystalline form of Schiff base, N-cyclohexyl-1-(3,4-dimethoxyphenyl)methanimine (CHADMB) was obtained from methanolic solution of cylohexylamine and (methylvanillin) 3,4dimethoxybenzaldehyde. Single crystal X-ray diffraction study reveals that the compound crystallized in monoclinic crystal system with P21/c space group having four molecules per unit cell (Z = 4). Hirshfeld surface (HS) analysis and 2D fingerprint plots reveals that weak non-covalent interactions are responsible for crystal packing. The UV-Vis spectroscopy study reveals that the optical band gap of the compound is 4.25 eV. The dielectric properties were studied as a function of frequency at room temperature and the results show that these properties can be exploited for optoelectronic applications. Thermal stability of the compound is revealed by thermogravimetric and differential thermogravimetric analysis. The in vitro antimicrobial activity against Gram negative (E. coli and P. aeruginosa and Gram positive (S. aureus ) bacterial strains and two fungal strains (C. albicans and A. niger) were studied by agar well diffusion method. It is found that the Schiff base is inhibiting the growth of the tested species to varying degrees. Molecular docking studies indicate that alkyl-pi and pi-pi weak interactions enhance the binding affinity of Schiff base-protein complexes. Molecular dynamics study reveals interaction of CHADMB complexed with bacterial protein, EC showed maximum stability which is in agreement with experimental result.Communicated by Ramaswamy H. Sarma.

New crystalline form of (N-cyclohexyl-1-(3,4-dimethoxyphenyl)methanimine Schiff base is synthesized.Synthesized compound is characterized by elemental analysis, SXRD, Raman, FT-IR, Mass, ¹H and ¹³C NMR spectroscopy.Band gap of the compound is calculated from absorption data.The dielectric properties of the compound are tested.Biological activity of the compound is tested against three bacterial and two fungal strains.Molecular docking and molecular dynamics studies were carried out to study the interaction of synthesized compound with various bacterial and fungal proteins.

Carvacrol Derivatives as Antifungal Agents: Synthesis, Antimicrobial Activity and in Silico Studies on Carvacryl Esters.

Chemical modifications of natural monoterpenoids to various derivatives have been reported to result in enhancement of biological activities when compared to parent compounds. In this context a well-known biocide and food additive, carvacrol, served as a basic scaffold onto which a phenolic functionality transformation by introducing acyl groups was performed. By using this simple methodology, we obtained a small series of 25 esters. For each of the obtained compounds we have performed structural characterization, in vitro antimicrobial testing and in silico calculation of physico-chemical, pharmacokinetic and toxicological properties. Despite numerous data on the synthesis and bioactivity of carvacryl ester lower homologues, there are scarce data on esters with acid components higher than C9, so that among 25 compounds, 10 were reported for the first time (spectral characterization for 12 are herein the first reported). Our research is also the first comprehensive study of carvacryl esters antifungal and of medium/long chain fatty acid esters antibacterial activities. Interesting result is that all the synthesized esters, regardless the nature of the R residue, have shown activity on fungal strain Aspergilus niger and on yeast Candida albicans comparable to carvacrol. Besides presented experimental data, implementation of in silico calculation of physico-chemical, pharmacokinetic and toxicological properties on the prepared compounds, may be valuable information in further research.

In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria.

Bacteria are the most common causative agents of ocular infections. Treatment with topical broad-spectrum antibiotics is recommended in severe cases. However, antibiotic resistance has become a major concern in recent years, although antibiotics are generally effective in treating ocular infections. Antibacterial compound screening is performed to identify alternative therapeutic options to antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of an ophthalmic solution containing ozonated oil. Strains of bacterial species with a multidrug resistance profile, which are responsible for a large proportion of ocular infections, were isolated and selected from different biological samples. The bacterial isolates were cultured, and ozonated oil was used to evaluate the inhibition zones at different time points. The treatment exhibited antibacterial activity against all the tested species. The effect was lower against the strains of Pseudomonas aeruginosa and more evident against Staphylococcus and Streptococcus spp. Our results suggest that the administration of ozonated oil may be a candidate agent to treat some infections of the ocular surface with a potential role in antimicrobial prophylaxis.

Comparative in vitro evaluation of the antimicrobial activities of povidone-iodine and other commercially available antiseptics against clinically relevant pathogens.

Aims: Antiseptics, such as povidone-iodine (PVP-I), play an important role in infection control across a wide range of clinical settings. This study aimed to evaluate the comparative in vitro efficacy and rate of onset of action of a range of formulations of PVP-I and other commonly used antiseptics. Methods: The antimicrobial efficacy of a range of antiseptics and antimicrobial agents used for skin, wound, vagina and oral antisepsis was evaluated according to the EU Standards DIN EN1276 and EN14476. The panel of organisms tested included bacterial and fungal pathogens and two enteroviruses (Coxsackievirus A16 [CA16] and Enterovirus 71 [EV71]). Results: All PVP-I products tested were highly efficacious in vitro (>99.99% kill rate) against a range of clinically relevant bacterial and fungal pathogens with rapid onset of action (30-60 seconds), at both high and low concentrations. By comparison, the efficacy of other antiseptics tested was generally reduced upon dilution. PVP-I products used in wound and oral care were found to be more effective in vitro against CA16 and EV71, and had a faster onset of action than most other agents tested. Conclusion: This study provides valuable insights into the in vitro efficacy of a range of commonly used antiseptics and may help inform the selection of appropriate antiseptics by healthcare professionals.

In vitro antimicrobial activity of a new ophthalmic solution containing povidone-iodine 0.6% (IODIM® ).

PURPOSE: To assess the in vitro antimicrobial activity of a new commercial ophthalmic solution containing povidone-iodine 0.6% (IODIM® ). METHODS: Staphylococcus aureus ATCC 43300, Pseudomonas aeruginosa ATCC 27853, three ocular bacterial isolates (1 S. epidermidis, 1 S. aureus, 1 P. aeruginosa) and five Candida species were used. The bacterial and fungal isolates were cultured on Columbia blood agar base plates and Sabouraud-dextrose agar plates, respectively and incubated overnight at 37°C. Bacterial and fungal suspensions in sterile saline solution were prepared to an optical density equal to 0.5 McFarland standard (approximately 108 CFU/ml). Suspensions of the isolates were made in IODIM® solution to obtain a final concentration of 106 CFU/ml. The suspensions were then distributed in conical tubes in a final volume of 1 ml and incubated at 37°C. At different time-points (1, 5, 10, 15, 20, 25, 30 min and 24 hr), 10 µl of each suspension was removed, seeded on Columbia blood agar base and Sabouraud-dextrose agar plates and then incubated for 24 hr at 37°C. Positive and negative controls were included in all experiments. RESULTS: After 5-min incubation, there was no bacterial growth on any plate. Conversely, IODIM® failed to kill the Candida isolates after 30 min' exposure and needed 24 hr to eradicate the organisms. CONCLUSION: IODIM® ophthalmic solution showed in vitro antimicrobial activity against S. epidermidis, S. aureus, P. aeruginosa and Candida species. Results suggest that it may be a potential candidate for the treatment of ocular surface infections and antimicrobial prophylaxis before intravitreal injections.

Genetic characterization and in vitro activity of antimicrobial combinations of multidrug-resistant Acinetobacter baumannii from a general hospital in China.

The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby-Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays. In total, 34 MDRAB strains were isolated and classified into 8 phenotypes A-H, according to their general drug susceptibilities. A total of 4 major genotypes (I-IV) were clustered at 60% a genotypic similarity threshold. High positive rates of ß-lactamase TEM-1, topoisomerase IV, oxacillinase (OXA)-23, AdeB family multidrug efflux RND transporter adeB, ß-lactamase AmpC, class 1 integrons (Int-1), 16S rRNA methylase rmtA, phosphotransferase aph(3), 16S rRNA methyltransferase armA were presented to exceed 90%, acetylyltransferase aac(3)-I, aac(6'-I, ant(3″)-I, 16S rRNA methylase rmtB, oxacillinase OXA-24 and metallo-ß-lactamase IMP-5 genes demonstrated positive rates of 29.4-85.29%, while adeRS two-component system was not observed in any strain. MEM+SCF I or SCF II primarily exhibited synergistic effects. AK+SCF I, AK+SCF II, MINO+SCF I, MINO+SCF II, MINO+CIP and MINO+MEM primarily presented additive effects. AK+CIP demonstrated 70.59% antagonism. The antibacterial activity of SCF I was superior compared with that of SCF II. The results indicated the polyclonal genetic epidemiological trend of MDRAB in the Second Xiangya Hospital, and verified the complexity of genetic resistance. In addition, combinations suggested to be efficacious were MEM+SCF I and MEM+SCF II, which were more effective compared with other combinations for the management of MDRAB infection.

Identification of Structurally Diverse Antimicrobials Through Sequential Application of Pharmacophore Modeling, Virtual Screening, Molecular Docking and In Vitro Microbiological Assay.

Dihydrofolate reductase enzyme has been an attractive biological target for the design and development of antimicrobials. Considering this, we have attempted to identify novel dihydrofolate reductase inhibitors through our well-defined in silico and in vitro work flow. An accurate and predictive pharmacophore model comprising of one hydrogen bond acceptor, two hydrophobic and one ring aromatic was developed and utilized as a query to search the National Cancer Institute and Maybridge database leading to retrieval of various compounds which were filtered on the basis of estimated activity, fit value and Lipinski's violation. Selected hits NSC3423, KM09759, NSC391, NSC2091 and HTS00630 were subjected to docking studies which resulted into visualization of potential interaction capabilities of hits in line to pharmacophoric features. The identified hits were evaluated for in vitro antimicrobial potential, and the results revealed that among all the five hits, NSC3423 is the most potent compound with activity against E. coli, P. aeruginosa, S. aureus, B. substilis, A. niger and F. oxysporum. On the other hand, KM09759, NSC391, NSC2091 and HTS00630 showed varying degree of activities against gram-positive, gram-negative and fungal strains.

Novel benzimidazol-2-ylidene carbene precursors and their silver(I) complexes: Potential antimicrobial agents.

Novel benzimidazolium salts were synthesized as N-heterocyclic carbene (NHC) precursors, these NHC precursors were metallated with Ag2O in dichloromethane at room temperature to give novel silver(I)-NHC complexes. Structures of these benzimidazolium salts and silver(I)-NHC complexes were characterized on the basis of elemental analysis, (1)H NMR, (13)C NMR, IR and LC-MS spectroscopic techniques. A series of benzimidazolium salts and silver(I)-NHC complexes were tested against standard bacterial strains: Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and the fungal strains: Candida albicans and Candida tropicalis. The results showed that benzimidazolium salts inhibited the growth of all bacteria and fungi strains and all silver(I)-NHC complexes performed good activities against different microorganisms.

Preparation of impurity C of doxycycline hyclate and its evaluation of in vitro antimicrobial activity and toxicity / 中国药科大学学报

@#This study aimed to isolate and prepare highly purified impurity C from doxycycline hyclate by a preparative HPLC method and to inspect the toxicity and in vitro antimicrobial activity of the impurity C of doxycycline hyclate. The solution of doxycycline hyclate treated with heat produced a solution containing 10% of impurity C which was firstly separated by the Sapphire C18(21. 2 mm×250 mm, 5 μm)column with 0. 1% acetic acid-acetonitrile(83 ∶17)as the mobile phase at 20 mL/min. Secondly, rotary evaporation of the eluted solution at the time of 8. 4 min was performed at 50 °C to remove organic solvent. Then the target product was prepared after freeze drying of evaporated solution adjusting pH to 1. 8 with formic acid. The target product was identified with ultraviolet absorbance(UV), infrared(IR), mass spectrometry(MS)and nuclear magnetic resonance(NMR), and its purity was be determined by HPLC. Meanwhile, cytotoxicity and genotoxicity in the Chinese hamster lung cells, toxicity on the development of zebrafish embryos and in vitro antimicrobial activity were compared among impurity C of doxycycline hyclate, doxycycline, metacycline and β-doxycycline. Results showed that prepared product was confirmed to be the impurity C of doxycycline hyclate. Its purity was 90. 1%, which had been the highest so far. In the cellular toxic tests and genetic toxic tests of Chinese hamster lung cells, impurity C of doxycycline hyclate, doxycycline, metacycline and β-doxycycline were somewhat toxic to Chinese hamster lung cells. Toxicity gradually decreased from doxycycline, impurity C of doxycycline hyclate, β-doxycycline to metacycline from -S9mix test results; toxicity gradually decreased from doxycycline, β-doxycycline, impurity C of doxycycline hyclate to metacycline from +S9mix test results; the aberration rate of all the tested related substances was less than 5%, and no obvious genotoxicity was found. According to test results of the development of zebrafish embryos, impurity C of doxycycline hyclate showed the strongest teratogenicity and lethality. Invitro antimicrobial tests revealed that impurity C of doxycycline hyclate had a weaker antimicrobial activity, and invitro antimicrobial activity potential of the tested compounds followed the order: metacycline, doxycycline, impurity C of doxycycline hyclate, β-doxycycline. Studies on safety and effectiveness indicated that impurity C of doxycycline hyclate belonged to toxic and ineffective impurity and need to be controlled individually in quality standard. A useful suggestion was given to revise the quality standard of doxycycline hyclate and its preparation in the current Pharmacopoeia of the People′s Republic of China.

Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity.

Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32 µM against Mycobacterium tuberculosis. The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide (MIC=2 µM). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide's MIC was 0.98 µM. None of the nitrosalicylanilides was active against Enterococcus sp. J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.

Salicylanilide diethyl phosphates: synthesis, antimicrobial activity and cytotoxicity.

A series of 27 salicylanilide diethyl phosphates was prepared as a part of our on-going search for new antimicrobial active drugs. All compounds exhibited in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium strains, with minimum inhibitory concentration (MIC) values of 0.5-62.5µmol/L. Selected salicylanilide diethyl phosphates also inhibit multidrug-resistant tuberculous strains at the concentration of 1µmol/L. Salicylanilide diethyl phosphates also exhibited mostly the activity against Gram-positive bacteria (MICs ≥1.95µmol/L), whereas their antifungal activity is significantly lower. The IC50 values for Hep G2 cells were within the range of 1.56-33.82µmol/L, but there is no direct correlation with MICs for mycobacteria.

In Vitro Antimicrobial Activity of Acacia catechu and Its Phytochemical Analysis.

UNLABELLED: Acacia catechu, commonly known as catechu, cachou and black cutch is an important medicinal plant and an economically important forest tree. The methanolic extract of this plant was found to have antimicrobial activities against six species of pathogenic and non-pathogenic microorganisms: Bacillus subtilis, Staphylococcus aureus, Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The maximum zone of inhibition (20 mm) was found to be exhibited against S. aureus. For this organism the minimum bactericidal concentration (MBC) of the crude extract was 1,000 µg/ml. The extract was found to be equally effective against gram positive and gram negative bacteria. The antimicrobial activity of the extract was found to be decreased during purification. The chemical constituents of organic plant extracts were separated by thin layer chromatography (TLC) and the plant extracts were purified by column chromatography and were further identified by Gas chromatography-mass selection (GC-MS) analysis. The composition of A. catechu extract had shown major components of terpene i.e. camphor (76.40%) and phytol (27.56%) along with other terpenes in minor amounts which are related with their high antibacterial and antifungal properties. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12088-011-0061-1) contains supplementary material, which is available to authorized users.

In Vitro Antibacterial Activity of Meropenem in Gram-negative bacilli / 中华医院感染学杂志

OBJECTIVE To investigate in vitro antibacterial activity of meropenem in Gram-negative bacilli isolated from clinical specimens.METHODS Gram-negative bacilli were isolated from various clinical specimens in our hosptial from Jan 2008 to Dec 2008.The identification test was determined by VITEK-32 Full Automated Microbiology Analyzer,the antimicrobiol susceptibility was detected by K-B method.RESULTS The resistance rate of Enterobacteriaceae to meropenem was extremly low.The resistance rates of Escherichia coli,Klebsiella pneumoniae and Enterobacter cloacae to meropenem were 0,27.6% and 4.2%.The resistance rates of Stenotrophomonas maltophilia,Burkholderia cepacia,Chryseobacterium meningosepticum,Pseudomonas aeruginosa and Acinetobacter baumannii to meropenem were 100.00%,48.81%,94.12%,21.85% and 31.72% respectively.CONCLUSIONS Meropenem has high in vitro antimicrobial activity to Enterobacteriaceae.but generally low to non-fermentative Gram-negative bacilli.