Ponnurengam Malliappan Sivakumar

Synthesis, antioxidant evaluation, and quantitative structure–activity relationship studies of chalcones

Synthesis, antioxidant activity, and quantitative structure–activity relationship (QSAR) of 25 of chalcone derivatives is reported here. They were synthesized by Claisen–Schmidt reaction and were characterized by FTIR, NMR, and mass spectroscopy. Antioxidant activity is evaluated through four different methods namely, superoxide radical-scavenging, hydrogen peroxide scavenging, reducing power, and DPPH radical-scavenging assays. Generally, compounds with –SCH3 and –OCH3 in the para position of the A-ring and –OH in the B-ring were more active than others. In few cases some of the compounds were more active than ascorbic acid or butylated hydroxytoluene. QSAR was developed correlating the antioxidant activity with the structural features of the compounds and the predictive capability of the models was estimated using internal and external validation methods. All the predictions were within the 99% confidence level. Spatial, structural, and lipophilic properties of the compounds determine their antioxidant properties.

Novel chalcones and 1,3,5‐triphenyl‐2‐pyrazoline derivatives as antibacterial agents

Novel sixteen chalcones and thirteen 1,3,5‐triphenyl‐2‐pyrazolines were synthesized and characterized using FT‐IR, HR‐Mass, NMR (1H‐NMR, 13C‐NMR, 135 DEPT, 1H–1H CoSY and 1H and 13C CoSY) and XRD. These compounds were evaluated for their antibacterial activity against six micro‐organisms, namely Bacillus subtilis NCIM 2718, Staphylococcus aureus NCIM 5021, Salmonella typhi NCIM 2501, Enterobacter aerogenes NCIM 5139, Pseudomonas aeruginosa NCIM 5029, and Proteus vulgaris NCIM 2813 by twofold dilution method using resazurin as the indicator dye. In the case of chalcones, compounds with hydroxyl and bromo substitutions in the B‐ring favor activity and benzyloxy substitution irrespective of its position in the A‐ring. In the case of 1,3,5‐triphenyl‐2‐pyrazolines, chloro substitution in the A‐ring favors activity. Hydrophilic/lipophilic balance of the compounds plays a major role in their antibacterial activity.

Synthesis, Biological Evaluation, Mechanism of Action and Quantitative Structure–Activity Relationship Studies of Chalcones as Antibacterial Agents

Forty‐eight chalcone analogs were synthesized and their in vitro antibacterial activity against Staphylococcus aureus NCIM 5021, Bacillus subtilis NCIM 2718, Phaseolus vulgaris NCIM 2813, Escherichia coli NCIM 2931, Salmonella typhi 2501 and Enterobacter aerogenes NCIM 5139 were evaluated by microdilution broth assay. Quantitative structure–activity relationships were developed for all the cases (r 2 = 0.68–0.79;  = 0.58–0.78; q 2 = 0.51–0.68; F = 13.02–61.51). Size, polarizability, electron‐donating/withdrawing and hydrophilic nature of the molecule determine the activity against these Gram‐positive and Gram‐negative bacteria. Staphylococcus aureus was the most and S. typhi was the least hydrophobic of these organisms. These chalcones act better against more hydrophobic organisms. The more active chalcones have log P between 1.5 and 3. Compound 24, one of the most active compounds, was found to act by damaging the cell wall of S. aureus. Slimicidal activity of five of the most active compounds (24, 31, 32, 34 and 37) was found to be in the range of 48–60% against S. aureus and 40–54% against E. coli. A correlation was observed among the hydrophobicity of the compounds, hydrophobicity of the bacterial cell surface and the antibacterial activity of the compound.

Antifungal Activity, Mechanism and QSAR Studies on Chalcones.

In this paper, the synthesis of 48 chalcones and their in vitro antifungal activity against Aspergillus flavus NCIM 594, Fusarium proliferatum NCIM1105, Aspergillus niger NCIM 596 and Candida tropicalis NCIM 3556 are reported. Predominantly, the active compounds (6, 9, 14, 27, and 47) against all four fungi have found to have electron withdrawing substitutions in their para substitution in B‐ring. Quantitative structure–activity relationship indicated that the antifungal activities are correlated with absorption distribution metabolism and excretion, electrophilicity, spatial and topological descriptors. The statistical measures such as r2 (0.68–0.71), r2‐adj (0.62–0.66), q2 (0.60–0.61) and F‐ratio (12–17) are reasonable. The data is divided into training and a test set, the former is used to develop the models, and the later is used to test their predictive capability. The predictions are found to be within the 99% confidence level except for two of the cases. SEM (scanning electron microscopy) and BacLight Live/Dead assay indicate that the chalcones act by disrupting the fungal cell wall.

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.

Experimental and QSAR of Acetophenones as Antibacterial Agents

Antibacterial activity of 20 acetophenone derivatives was evaluated against two Gram‐positive and three Gram‐negative organisms, namely, Bacillus subtilis NCIM 2718, Staphylococcus aureus NCIM5021, Salmonella typhi NCIM2501, Enterobacter aerogenes NCIM5139, and Proteus vulgaris NCIM2813 by two‐fold dilution method. The most active amongst this group of compounds were 4‐methyl, 2‐hydroxy, 3‐bromo, 4‐ethoxy, 3‐nitro and 4‐nitro acetophenones. Quantitative structure–activity relationships were developed by dividing the data into training and validation sets, the former was used to develop and the latter was used to test the models. Spatial, electronic and topological descriptors were predominantly found to influence the activity. The statistical measures such as r 2 (0.76–0.91), cross‐validated r 2 (0.56–0.85), F‐ratio and predicted residual sum of square values were found to be in the acceptable range. The developed models were able to predict the activity of the validation data set within the 99% confidence limit (except for two data points). 4‐Nitroacetophenone was found to be the most slimicidal in nature. Bacterial Adhesion to Hydrocarbons (BATH) assay indicated that Staphylococcus aureus NCIM5021 had the most hydrophobic cell surface of these five organisms. Cell surface hydrophobicity of organisms also had an impact on the antibacterial activity of the acetophenones.

Immobilization of subtilisin on polycaprolactam for antimicrobial food packaging applications.

Subtilisin was immobilized on polycaprolactam and used for food packaging applications to reduce the transference of microorganisms from the packaging material to the packaged food material. The optimized conditions for subtilisin immobilization was as follows: pH, 8; temperature, 4 °C; glutaraldehyde, 0.5%; incubation time, 25 h; and subtilisin concentration, 600 μL. The formation of -CH═N- at 1576 cm(-1) in the Fourier transform infrared (FTIR) spectrum confirmed the immobilization. Subtilisin-immobilized polycaprolactam (SIP) exhibited the highest residual activity of 106.67 ± 4.41% and 104.67 ± 0.88% at 40 °C and pH 8 and retained residual activity of 94% at the end of 56 days when compared to 21.33 ± 4.10% in the case of free subtilisin. SIP significantly (p < 0.05) lowered the colony forming units (CFU), dry weight, and protein and carbohydrate contents in bacterial and fungal biofilm. Practical application of the SIP on ham steaks at 4 and 20 °C showed a 2-3 times reduction of Staphylococcus aureus as well as Escherichia coli cells in the range of p < 0.05.

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, (>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.

Impact of Topological and Electronic Descriptors in the QSAR of Pyrazine Containing Thiazolines and Thiazolidinones as Antitubercular and Antibacterial Agents

Quantitative structure activity relationships (QSAR) were developed relating the 14th and 21st day antituberculosis activity against H37Rv strain of Mycobacterium tuberculi and antibacterial activity against Staphylococcus aureus ATCC3750, Bacillus subtilis 6633, Escherichia coli ATCC3750, and Salmonella typhi NCTC786 of 55 pyrazine containing thiazolines and thiazolidinones, with the molecular descriptors. The developed models were able to fit the data well (r2 = 0.69–0.87) and had reasonable predictive capability (q2 > 0.62). The data were also divided into a training set and a test set, the former was used to develop the QSAR and the latter was used to evaluate the predictive capability of these developed models. In all the cases, the models were able to predict the test data set reasonably well. Predominantly, pyrazine ring is well‐known for its antimycobacterial activity and hence these equation could be used to design newer analogues with higher activity. These compounds also possess both antitubercular and antibacterial activity. Descriptors pertaining to electronic, topology, and hydrophobicity of the molecules appear in the model equations.

Design of a papain immobilized antimicrobial food package with curcumin as a crosslinker.

Contamination of food products by spoilage and pathogenic microorganisms during post process handling is one of the major causes for food spoilage and food borne illnesses. The present green sustainable approach describes the covalent immobilization of papain to LDPE (low density polyethylene), HDPE (high density polyethylene), LLDPE (linear low density polyethylene) and PCL (polycaprolactam) with curcumin as the photocrosslinker. About 50% of curcumin and 82-92% of papain were successfully immobilized on these polymers. After 30 days, the free enzyme retained 87% of its original activity, while the immobilized enzyme retained more than 90% of its activity on these polymers. Papain crosslinked to LLDPE exhibited the best antibiofilm properties against Acinetobacter sp. KC119137.1 and Staphylococcus aureus NCIM 5021 when compared to the other three polymers, because of the highest amount of enzyme immobilized on this surface. Papain acts by damaging the cell membrane. The enzyme is able to reduce the amount of carbohydrate and protein contents in the biofilms formed by these organisms. Meat wrapped with the modified LDPE and stored at 4°C showed 9 log reduction of these organisms at the end of the seventh day when compared to samples wrapped with the bare polymer. This method of crosslinking can be used on polymers with or without functional groups and can be adopted to bind any type of antimicrobial agent.