2-Methoxy-2',4'-dichloro chalcone as an antimicrofoulant against marine bacterial biofilm.

Marine paint mixed with 2-methoxy-2',4'-dichloro chalcone is able to considerably reduce the formation of biofilm by Vibrio natriegens, a marine bacterium, on polycarbonate (PC), polymethylmethacrylate (PMMA) and glass fiber reinforced plastic (GFRP). These polymers have been selected for the study, since they have wide marine applications. Surfaces coated with dichloro chalcone containing marine paint had the lowest number of colony forming units (CFU) (1-5×10(6)), proteins (20-30 µg/cm2) and carbohydrates (5-10 µg/cm2) attached to them after 28 days of exposure to the organism when compared to surfaces coated with CuSO4 mixed paint (20-40×10(6) CFU/ml, proteins of 50-60 µg/cm2 and carbohydrates of 40-50 µg/cm2) or plain marine paint (30-40×10(6) CFU/ml, proteins of 120-150 µg/cm2 and carbohydrates of 40-60 µg/cm2). At the end of the study period, the biofilm on PMMA was 7, 10 and 12 µm thick on chalcone, copper and plain paint coated surfaces, respectively. The first two paints increased the surface roughness but decreased the surface hydrophobicity when compared to the plain paint. Large number of dead cells was found on the chalcone mixed and predominantly live cells were found on plain paint coated surfaces. 15% of dichloro chalcone had leached out of PMMA surface after 28 days. The low amount of biofilm formed in the presence of dichlorochalcone can be associated to its antibacterial and slimicidal activity and also its ability to reduce the hydrophobicity of the surface. This dichlorochalcone appears to be a novel agent for decreasing the formation of marine biofilm.

Synthesis, antibacterial activity evaluation and QSAR studies of novel dispiropyrrolidines.

A series of novel dispiropyrrolidines have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from sarcosine and isatin with the dipolarophile 3-benzylidene-1-methyl-pyrrolidine-2,5-dione. Their antibacterial activity was evaluated against Bacillus subtilis NCIM 2718, Staphylococcus aureus NCIM5021, Salmonella typhi NCIM2501, Pseudomonas aeruginosa NCIM 5029 and Proteus vulgaris NCIM2813 by two fold dilution method. Compound 6e exhibits reasonably good activity and compound 6c exhibits poor activity against all the organisms. The QSAR's were developed for all antibacterial activities. The models had either one or two descriptors (r(2) = 0.81-0.97, r(adj)(2)=0.75-0.96, q(2) = 0.57-0.92, F-ratio = 12.73-162.76). Topology, shape, charge distribution and hydrophobic nature of the molecules had pronounced effect on their antibacterial activity.

Antibacterial activity and QSAR of chalcones against biofilm-producing bacteria isolated from marine waters.

Biofouling in the marine environment is a major problem. In this study, three marine organisms, namely Bacillus flexus (LD1), Pseudomonas fluorescens (MD3) and Vibrio natriegens (MD6), were isolated from biofilms formed on polymer and metal surfaces immersed in ocean water. Phylogenetic analysis of these three organisms indicated that they were good model systems for studying marine biofouling. The in vitro antifouling activity of 47 synthesized chalcone derivatives was investigated by estimating the minimum inhibitory concentration against these organisms using a twofold dilution technique. Compounds C-5, C-16, C-24, C-33, C-34 and C-37 were found to be the most active. In the majority of the cases it was found that these active compounds had hydroxyl substitutions. A quantitative structure-activity relationship (QSAR) was developed after dividing the total data into training and test sets. The statistical measures r(2), [image omitted] (>0.6) q(2) (>0.5) and the F-ratio were found to be satisfactory. Spatial, structural and electronic descriptors were found to be predominantly affecting the antibiofouling activity of these compounds. Among the spatial descriptors, Jurs descriptors showed their contribution in all the three antibacterial QSARs.

Synthesis, antibacterial activity evaluation and QSAR studies of novel dispiropyrrolidines.

A series of novel dispiropyrrolidines have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from sarcosine and isatin with the dipolarophile 3-benzylidene-1-methyl-pyrrolidine-2,5-dione. Their antibacterial activity was evaluated against Bacillus subtilis NCIM 2718, Staphylococcus aureus NCIM5021, Salmonella typhi NCIM2501, Pseudomonas aeruginosa NCIM 5029 and Proteus vulgaris NCIM2813 by two fold dilution method. Compound 6e exhibits reasonably good activity and compound 6c exhibits poor activity against all the organisms. The QSAR's were developed for all antibacterial activities. The models had either one or two descriptors (r2 = 0.81-0.97, , q2 = 0.57-0.92, F-ratio = 12.73-162.76). Topology, shape, charge distribution and hydrophobic nature of the molecules had pronounced effect on their antibacterial activity.

Novel 1,3,5-triphenyl-2-pyrazolines as anti-infective agents.

Sixteen 1,3,5-triphenyl-2-pyrazolines were synthesized and their anti-infective activities (against Mycobacterium tuberculosis H(37)Rv, six bacterial and four fungal strains) were tested. Only compound with SO(2)CH(3) in the para position of the A-ring was active against the tubercular strain at 100 microg/ml concentration. All compounds showed good anti infective activity against Escherichia coli and poor activity against Staphylococcus aureus. Compounds 4, 12, 13 and 14 exhibited reasonable activity against all the organisms tested (<0.309 microM except against S. aureus. The activity of these compounds correlated with their lipophilic/hydrophilic nature. Compounds 4, 10 and 16 showed very good activity (>88% reduction) against four fungi studied at 2mg/ml. All these compounds possess halogen substitutions. Compound 11 showed very high activity (>90%) against three fungi. Majority of the compounds showed more than 90% inhibition against one or two fungi. Since pyrazolines are reported to inhibit the activity of p-glycoprotein, they may prevent drug resistance developed by microorganism.

Quantitative structure-activity relationships for commercially available inhibitors of COX-2.

Quantitative structure activity relationship (QSAR) studies of selective COX-2 inhibitors of commercial interest (drugs in market and on clinical trials) were performed. The COX-2 inhibitory activity (pIC(50)=-logIC(50)) of these twelve compounds was correlated with nineteen descriptors including steric, electronic and constitutional parameters. pIC(50) activity showed high positive correlation with both volume and HOMO (Highest occupied molecular orbital). A Biparametric model was developed that included both these descriptors. The predictive capability (q(2)= 0.66) of this equation was satisfactory. So it can be used to design newer templates or modify existing templates. Volume is an important parameter for the selective COX-2 inhibitory activity, because the secondary pocket in the active site of this enzyme is bigger than the active site of COX-1 enzyme (by 17%). HOMO is a measure of the nucleophilicity of the molecule and a molecule with high HOMO energy is ready to donate its electrons and thus is more reactive than molecule with low values. Binding studies were performed between the COX-2 enzyme and these molecules. The inhibitory activity increased with decrease in binding energy (or interaction energy) between the compounds with the COX-2 enzyme (with a correlation coefficient = -0.65). Calculated Log BBB (Blood Brain barrier), Log P (octonol water partition) and HBD (hydrogen bond donor) values were in the acceptable range (i.e., BBB = -1 to 0.3; LogP= 0 to 5; HBD < 5).

Synthesis, antimycobacterial activity evaluation, and QSAR studies of chalcone derivatives.

In order to develop relatively small molecules as antimycobacterial agents, twenty-five chalcones were synthesized, their activity was evaluated, and quantitative structure-activity relationship (QSAR) was developed. The synthesis was based on the Claisen-Schimdt scheme and the resultant compounds were tested for antitubercular activity by luciferase reporter phage (LRP) assay. Compound C(24) was found to be the most active ( approximately 99%) in this series based on the percentage reduction in Relative Light Units at both 50 and 100 microg/ml levels, followed by compound C(21). Four compounds at the 50 microg/ml and eight compounds at the 100 microg/ml showed activity above 90% level. QSAR model was developed between activity and spatial, topological, and ADME descriptors for the 50 microg/ml data. The statistical measures such as r, r(2), q(2), and F values obtained for the training set were in acceptable range and hence this relationship was used for the test set. The predictive ability of the model is satisfactory (q(2)=0.56) and it can be used for designing similar group of compounds.