Design, synthesis of pyridine coupled pyrimidinone/pyrimidinthione as anti-MRSA agent: Validation by molecular docking and dynamics simulation.

Methicillin Resistant Staphylococcus aureus (MRSA) is a major cause of severe hospital and infections acquired by the population and related morbidity and mortality. In this unique situation, there is a need of dynamic strong drug candidates to control MRSA diseases. Thus, the present work focuses on the synthesis and characterization of pyrimidinones and pyrimidinthiones coupled pyridine derivatives as anti-MRSA agent. The synthesized compounds were characterized by different spectroscopic techniques and evaluated against MRSA strain. Among them, 4e and 4 g possessed better antibacterial activity with MIC values of 10 µg and 8 µg respectively. The key determinant of the wide range beta-lactam resistance in MRSA strains is the Penicillin-Binding Protein 2a (PBP2a) but the gene encodes PBP2a which has a low affinity towards ß-lactam antibiotics. Because of this, the present investigation focused on the mechanism of PBP2a protein binding studies by in-silico studies. The synthesized compounds showed very good interactions with PBP2A compared with standard drug Vancomycin, among them compound 4 g showed better interaction with the binding score of -9.8 kcal/mol. Antibacterial activity was validated with molecular docking and molecular dynamic simulation. Simulation results revealed that protein-ligand interactions of 4 g compound stably sustained up to 20,000ps.Communicated by Ramaswamy H. Sarma.

Synthesis and characterization of chitosan silver nanoparticle decorated with benzodioxane coupled piperazine as an effective anti-biofilm agent against MRSA: A validation of molecular docking and dynamics.

Biomaterial research has improved the delivery and efficacy of drugs over a wide range of pharmaceutical applications. The objective of this study was to synthesize benzodioxane coupled piperazine decorated chitosan silver nanoparticle (Bcp*C@AgNPs) against methicillin-resistant Staphylococcus aureus (MRSA) and to assess the nanoparticle as an effective candidate for antibacterial and anti-biofilm care. Antibacterial activity of the compound was examined and minimum inhibitory concentration (MIC) was observed at (10.21 ± 0.03 ZOI) a concentration of 200 µg/mL. The Bcp*C@AgNPs interferes with surface adherence of MRSA, suggesting an anti-biofilm distinctive property that is verified for the first time by confocal laser microscopic studies. By ADMET studies the absorption, distribution, metabolism, excretion and toxicity of the compound was examined. The interaction solidity and the stability of the compound when surrounded by water molecules were analyzed by docking and dynamic simulation analysis. The myoblast cell line (L6) was considered for toxicity study and was observed that the compound exhibited less toxic effect. This current research highlights the biocidal efficiency of Bcp*C@AgNPs with their bactericidal and anti-biofilm properties over potential interesting clinical trial targets in future.

Development of piperazine-1-carbothioamide chitosan silver nanoparticles (P1C-Tit*CAgNPs) as a promising anti-inflammatory candidate: a molecular docking validation.

Natural products are important leads in drug discovery. The search for effective plant-derived agents or their synthetic analogues has continued to be of interest to biologists and chemists for a long time. Herein, we have synthesized a novel compound, P1C, and P1C-Tit*CAgNPs from chitosan; P1C is a precursor and an anti-inflammatory candidate, which has been validated by molecular docking studies. The synthesized P1C-Tit*CAgNPs showed monodisperse, spherical, and cationic nature and antioxidant properties, protecting destabilization of the erythrocyte membrane by the azo compound 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH); the involvement of NPs as a protective agent for biomolecules, such as DNA and protein, followed by the treatment of NPs with AAPH was confirmed. The inhibition of cellular damage and leakage of cellular inflammatory agents was confirmed by AFM, SEM, TEM, SDS-PAGE, LDH, and PLA2 enzyme inhibition via in vitro studies. The anti-inflammatory property of P1C was further validated by in silico molecular docking studies and showed that, the P1C best pose aligned to PLA2 compared to standard drug. The significant anticancer property of P1C-Tit*CAgNPs was confirmed against MCF7, U373, and C6 cancer cell lines. Thus, the present study highlights the synthesized P1C in P1C-Tit*CAgNPs as a target PLA2-specific anti-inflammatory candidate, and further tuning of small and development-functionalized nanoparticles has a great future in medicine; hence, their clinical applications are warranted.

Synthesis of novel benzodioxane midst piperazine moiety decorated chitosan silver nanoparticle against biohazard pathogens and as potential anti-inflammatory candidate: A molecular docking studies.

Nanoparticles (NPs) are currently being investigated along with the use of biodegradable polymer containing active agents in many areas of medicine for targeted applications. The present study was aimed to synthesize novel compound Benzodioxane midst piperazine (BP) and characterization of a BP decorated chitosan silver nanoparticles (BP*C@AgNPs) and shown effective against hazardous pathogens, and also having anti-inflammatory property. It was further evaluated for molecular docking proofs, and toxicity. The BP*C@AgNPs had spherical shape with size of 36.6nm with wide biocidal activity against hazardous Gram-positive and Gram-negative bacteria with excellent inhibition at 100µg/mL for S. aureus (10.08±0.05mm ZOI), and E. coli (10.03±0.04mm ZOI) compared to antibiotic Streptomycin. The anti-inflammatory activity exhibited IC50 value of 71.61±1.05µg/mL for BP*C@AgNPs compared to indomethacin (IC50=40.15±1.21µg/mL). Also, the docking study of BP showed excellent score for COX1 and DNA gyrase. This in silico study confirmed the achieved efficacy of BP, with less toxicity against normal PMBCs in vitro and in vivo studies. This study concludes that, the novel synthesized BP*C@AgNPs had excellent biocidal property and as anti-inflammatory candidate revealed by docking studies, it confirms BP*C@AgNPs for first-class therapeutic applications in the area of medicinal nanotechnology for the coming days.

An investigation of social judgments made by young adults toward appearance of dental fluorosis.

BACKGROUND: Smile is a crucial factor in creating a good first impression. However conditions like dental fluorosis hamper the esthetics of teeth. This study was conducted to find out whether young adults attribute socially relevant characteristics to people with dental fluorosis. MATERIALS AND METHODS: A total of 150 young adults were presented with images of individuals with different severity levels of dental fluorosis along with images of normal tooth appearance on a computer screen. They had to attribute various socially relevant characteristics to these images. Images were digitally manipulated to simulate dental fluorosis. Images were displayed on a computer screen and Visual Basic Software was used to record the participants' responses as well as the time taken to respond. The time taken to respond or response latency indicates the response strength. STATISTICAL ANALYSIS: A chi-square test was used to test the association between the dental appearances and the socially relevant characteristics. A Mann--Whitney test was used to compare the time taken to respond. RESULTS: As the severity of fluorosis increases, participants attribute less and less of positive characteristics. Attribution of negative characteristics also increases with the severity of dental fluorosis. For images with moderate and severe fluorosis, respondents took more time to accept positive characteristics and less time to reject positive characteristic. This means that the participants felt strongly when rejecting positive characteristics in these images. CONCLUSION: Social judgments are made by young adults when viewing digitally manipulated images of different levels of fluorosis.

Role of score for neonatal acute physiology (SNAP) in predicting neonatal mortality.

OBJECTIVES: To assess the validity of SNAP in predicting the outcome in terms of mortality and duration of hospital stay. The study was also undertaken to evolve the best cut-off SNAP scores for predicting mortality in different individual neonatal conditions. METHODS: 295 consecutive newborn admitted to NICU during an eleven month period were evaluated with the investigations required as per the specifications of SNAP. Neonates who succumbed within 24 hours of admission and those who were shifted to the NICU for observation purposes were excluded. RESULTS: In general, SNAP correlated well with mortality; the sensitivity and specificity of SNAP score > 15 in predicting mortality were 63% and 95% respectively. The positive and negative predictive values were 72% and 92.5% respectively. Very low birth weight babies and ventilated preterm neonates had higher mortality and the best cut-off SNAP score for predicting mortality in these groups was 10. In all the other groups, SNAP score > 15 correlated well with higher mortality. By using multiple regression analysis on three variables including birth weight, gestational age and SNAP, SNAP was found to show the best correlation with mortality. On correlating SNAP with duration of hospital stay, 76.8% of the surviving neonates with SNAP < 16 stayed for < 15 days, whereas the rest stayed longer despite low SNAP. All the 9 babies with SNAP > 15 who survived stayed for > 15 days. CONCLUSIONS: SNAP is a measure of illness severity and correlates well with neonatal mortality. SNAP may assist the clinician in explaining the probable outcome and therapeutic intervention needed and the cost of treatment to the parents. SNAP scores > 10 in VLBW babies and > 15 in others are associated with higher mortality.

Menetrier's disease.

An 8-year-old girl presented with persistent vomiting, pain abdomen and generalized edema. Barium studies and gastroscopy suggested hypertrophic gastropathy. Histopathological examination pointed the diagnosis towards Menetrier's Disease. There was spontaneous remission and the child required only supportive therapy.

Red cell distribution width in the diagnosis of iron deficiency anemia.

OBJECTIVE: 1. To compare peripheral smear (PS) and Red cell distribution width (RDW) in diagnosis of Iron deficiency anemia (IDA) in various grades. 2. To study the changes in RDW and PS after therapy. METHODS: Children in the age group of six months to five years with microcytic (MCV<80fl) anemia (Hemoglobin <11 g%) were evaluated. Those who had received blood transfusion and /or were already on iron therapy were excluded. Evaluation included clinical examination, complete blood count (CBC), RDW estimation microscopic examination of peripheral smear, measurement of serum iron and transferrin saturation. Children with IDA were treated with oral iron for 8 weeks and PS, CBC including RDW were repeated. RESULT: Of the 100 children evaluated, 89 had IDA. 48% had mild, 42% had moderate and 10% had severe anemia. Transferrin saturation correlated with severity of anemia. Peripheral smear showed microcytosis and hypochromia in all cases with severe anemia, 61.5% and 22.5% of those with moderate and mild anemia respectively. RDW was suggestive of iron deficiency in 100%, 82.05% and 100% of patient with mild, moderate and severe anemia respectively. CONCLUSION: In the diagnosis of mild and moderate iron deficiency anemia, RDW had a higher sensitivity than PS. Red cell morphology, Hb, PCV and RDW showed significant improvement after iron-therapy.