Dimer stilbene, a resveratrol analogue exhibits synergy with antibiotics that target protein synthesis in eradicating Staphylococcus aureus infection.

Antibiotic resistance has become a major hurdle for successful treatment of several infections resulting in increased length of stay in hospitals and mortality. One of the notorious pathogens that wreaks havoc due to antibiotic resistance is Staphylococcus aureus. There is an urgent need to discover and understand the function of newer molecules that could serve in the arsenal to combat these bacteria. Our recent work identified important structural determinants of stilbenes that could aid in better antibacterial activity and identified Dimer stilbene (DS) as a potent inhibitor of S. aureus. Contrasting reports exist in literature about the combination of stilbenes with different antibiotics. In this study we evaluated the ability of DS to synergize with different classes of antibiotics. A screen revealed DS exhibited positive co-operativity with antibiotics that target protein synthesis. DS exhibited synergy with the aminoglycoside kanamycin and additive effect with tetracycline. Resistance generation to DS was null while to that of kanamycin was rapid. Kanamycin resistant S. aureus was equally susceptible to DS compared to wildtype. The efficacy of DS against clinical isolates susceptible and resistant to methicillin were similar. Laboratory generated kanamycin resistant strain and clinical strains were sensitized to kanamycin by pre-treatment with DS. DS cured S. aureus infection in mice as a standalone drug as well as in conjunction with kanamycin. Synergy with kanamycin was also observed in other stilbenes apart from DS. Thus our study reveals stilbenes could be exploited towards combating S. aureus infections either as standalone drugs or in combination with existing antibiotics.

Antibacterial activity of resveratrol structural analogues: A mechanistic evaluation of the structure-activity relationship.

Structure-activity relationship (SAR) studies have led to significant improvement in desirable biological activity in different classes of molecules. A general consensus about the substitutions that improve the activity remains elusive in stilbene class of molecules especially in regard to antibacterial activity. Lack of this knowledge remains a major hurdle in developing stilbene based antibacterial molecules. A panel of gram positive and gram negative bacteria were employed for screening the comparative efficacy of the stilbenes. In addition, the mechanisms that contribute to the antibacterial activity were investigated and correlated to structural changes. Employing the notorious nosocomial agent S. aureus we show how changes in structure alters not only the antibacterial activity but also the underlying mechanisms. Antibacterial activity by CLSI (Clinical & Laboratory Standards Institute) guidelines, oxidative stress and membrane damage by fluorescence based methods, DNA binding by spectroscopy, DNA cleavage by gel electrophoresis, substrate efflux by efflux mutant and cell wall damage by scanning electron microscopy were investigated. Antibacterial activity varied drastically among stilbenes bearing different functional groups. The best stilbenes in terms of activity also scored higher in one or more molecular events that contribute to cell death. Stilbenes superior to resveratrol in antibacterial acitvity were identified and probable causes for better activity were also identified. Our study revealed dimerization, halogenation and hydroxy group in conjunction with methoxy group resulted in the best antibacterial molecules. Design of stilbene based drugs would be benefitted with the outcome and rationale presented in the current investigation.

A novel design for porphyrin based D-s-A systems as molecular rectifiers.

Two Si-based hybrid self-assembled monolayers of porphyrin based on a D-s-A system were synthesized by electro-grafting. The monolayers showed a stable and reversible rectification at room temperature. The monolayer fabricated using a porphyrin with an eleven-carbon alkyl chain linker was comparatively more compact and exhibited a 105 times higher rectification ratio (RR) relative to another similar system that had a six-carbon alkyl chain linker, possibly because of the compact packing.

Green synthesis and bioactivity of 2-amino-4H-chromen-4-yl-phosphonates.

A simple and efficient one pot synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives has been accomplished by the condensation of salicylaldehyde, malononitrile/ethylcyanoacetate and triethyl phosphite/trimethyl phosphite in the presence of molecular iodine as catalyst in water at room temperature. All the reactions were very clean and the products were obtained in very good to excellent yields. The title compounds are characterized by IR, 1H-, 13C-, 31P-NMR and mass spectra, also studied their antimicrobial and antioxidant activity.

Facile synthesis, antioxidant and antimicrobial activity of amino methylene bisphosphonates.

A green and efficient preparation method for the amino bisphosphonates is accomplished by simple mixing and stirring of diethylphosphite, triethylorthoformate and various amines in the presence of amberlyst-15 as catalyst at room temperature under solvent free conditions. The title compounds are characterized by IR, (1)H-, (13)C-, (31)P-NMR and mass spectra, also studied their antimicrobial and antioxidant activity.

Synthesis, anti-bacterial and anti-oxidant properties of thiadiazaphosphol-2-ones.

4-Amino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) underwent facile condensation with various phosphorus dichlorides (2a-j) in the presence of triethylamine in dry tetrahydrofuran at 60-65 degrees C and afforded corresponding thiadiazaphosphol-2-ones (3a-j). Their chemical structures were characterized using IR, (1)H-, (13)C-, (31)P-NMR and Mass spectral studies. All the title compounds were screened for antioxidant properties by radical scavenging methods such as 1,1-diphenyl-2-picryl hydrazyl (DPPH), hydroxyl and lipid peroxidation. They exhibited potent in vitro antioxidant activity dose dependently. Their bioassay showed them to possess significant antibacterial activity.