Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-β-boswellic acid from Boswellia serrata

<p>Abstract</p> <p>Background</p> <p>Boswellic acids are pentacyclic triterpenes, which are produced in plants belonging to the genus <it>Boswellia</it>. Boswellic acids appear in the resin exudates of the plant and it makes up 25-35% of the resin. β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid have been implicated in apoptosis of cancer cells, particularly that of brain tumors and cells affected by leukemia or colon cancer. These molecules are also associated with potent antimicrobial activities. The present study describes the antimicrobial activities of boswellic acid molecules against 112 pathogenic bacterial isolates including ATCC strains. Acetyl-11-keto-β-boswellic acid (AKBA), which exhibited the most potent antibacterial activity, was further evaluated in time kill studies, postantibiotic effect (PAE) and biofilm susceptibility assay. The mechanism of action of AKBA was investigated by propidium iodide uptake, leakage of 260 and 280 nm absorbing material assays.</p> <p>Results</p> <p>AKBA was found to be the most active compound showing an MIC range of 2-8 μg/ml against the entire gram positive bacterial pathogens tested. It exhibited concentration dependent killing of <it>Staphylococcus aureus </it>ATCC 29213 up to 8 × MIC and also demonstrated postantibiotic effect (PAE) of 4.8 h at 2 × MIC. Furthermore, AKBA inhibited the formation of biofilms generated by <it>S. aureus </it>and <it>Staphylococcus epidermidis </it>and also reduced the preformed biofilms by these bacteria. Increased uptake of propidium iodide and leakage of 260 and 280 nm absorbing material by AKBA treated cells of <it>S aureus </it>indicating that the antibacterial mode of action of AKBA probably occurred via disruption of microbial membrane structure.</p> <p>Conclusions</p> <p>This study supported the potential use of AKBA in treating <it>S. aureus </it>infections. AKBA can be further exploited to evolve potential lead compounds in the discovery of new anti-Gram-positive and anti-biofilm agents.</p

Tandem Catalysis by Lipase in a Vinyl Acetate-Mediated Cross-Aldol Reaction

The lipase Novozym435 (0.6% w/w) was used in tandem with organocatalysts in a first vinyl/isopropenyl acetate-mediated aldol reaction. The reaction was facilitated through the lipase-catalyzed in situ generation of acetaldehyde/acetone. The importantfeatures of the present methodology include the mild and facile reaction conditions, regenerability of the lipase, comparatively high yields and minimal side product formation

An excellent protocol for the synthesis of benzopyrans using basic resin under MWI

1561-1564A convenient, microwave promoted novel protocol for the synthesis of diverse kinds of substituted benzopyrans from the corresponding variety of substituted hydroxy acetophenones and keto compounds using Amberlite IRA 400 resin (basic resin) under solvent-free conditions, has been developed. This protocol is mild and more efficient than the other reported methods

Indium trichloride promoted stereoselective synthesis of O-glycosides from trialkyl orthoformates

A novel, highly stereoselective method for O-glycosylation of glycals and glycosylbromides is developed using orthoformates as acceptors in the presence of InCl3 to afford the corresponding O-glycopyranosides in 66–94% yield. Both perbenzyl and peracetyl glycals afford the corresponding 2,3-unsaturated-O-glycosides with high a-selectivity. Stoichiometric amounts of orthoformates are sufficient to bring about this transformation instead of large excesses of alcohols

Enzymatic resolution of naproxen

Trichosporon sp. (TSL), a newly found strain isolated from a locally fermented cottage cheese has been found to be highly stereoselective in the resolution of(S)-(+)-naproxen (ee >99%, E�500) from the corresponding racemic methyl ester. The process of resolution using whole cells has been scaled up to multi-kg level. Optimization of experimental conditions including downstream processing at 80–100 g/L substrate concentration with >90% recovery has been achieved. Changes in the physical parameters such as the particle size of the substrate play an important role in the resolution kinetics. A new strain of Trichosporon sp. having high cell density in cultivation (>60 g dry cell mass L−1 in 14–16 h) is found to be sufficiently stable for two years in dry powder form at 5–8°C. The viability of the resolution process has been further improved by the development of a simple racemization process for the enriched (R)-(−)-ester

Highly Regio- and Stereoselective One-Pot Synthesis of Carbohydrate-Based Butyrolactones

The use of manganese(III) acetate allows the direct synthesis of diverse arrays of [4.3.0] bicyclic carbohydrate-based γ-lactone building blocks from glycals. A mechanism to explain the high regio- and stereoselectivity is proposed. The new reaction has the potential to generate libraries for biological screening

Facile synthesis of various 4-carboxylic acid derivatives and their amide analogues of benzopyrans

605-610A series of 4-carboxyalkyl amide derivatives of benzopyrans 6a-d and 7a-d have been prepared in 40-64% overall yields. In the proposed synthetic strategy, the key intermediate 4-methyl substituted chroman 3 is obtained by condensing substituted phenol and mesityl oxide in presence of PPA. The required carboxylic acid function has been introduced at C-4 in benzopyran ring through a novel route

Arthrobacter sp. lipase immobilization on magnetic sol 13gel composite supports for enantioselectivity improvement

A bacterial lipase from Arthrobacter sp. (ABL: IIIM Jammu, India strain, MTCC No. 5125) has been immobilized on non-magnetic (Type A) and magnetic (Type B) supports derived from copolymerization of 3-aminopropyltriethoxysilane and tetraethylorthosilicate.Immobilized ABLpresented 21 1334 mg/g protein binding providing 30 1375 units/g activity in Type A non-magnetic composites and 24 1345 mg/g protein binding providing 35 1390 units/g activity with Type B supports containing magnetic particles. Immobilized ABL preparations have shownenhanced stability at pH5 139 and temperature up to 70 8C whereas free ABL is unstable under these conditions. Improved hydrolytic conversion as well as enantioselectivity were observedwith acylfluoxetine intermediate (ethyl3-hydroxy-3-phenylpropanoate alkyl acylates) andchiral auxiliaryacyl 1-phenyl ethanol usingimmobilized ABL derivatives (ee�99%; 3 134-fold increase in E-values) as compared to ABL enzyme/cells (ee 93 1398%). Introduction of magnetic particles in these supports has led to easier separation process with high product recovery yields

Arthrobacter sp. lipase immobilization for improvement in stability and enantioselectivity

Arthrobacter sp. lipase (ABL, MTCC no. 5125)is being recognized as an efficient enzyme for the resolution of drugs and their intermediates. The immobilization of ABL on various matrices for its enantioselectivity,stability, and reusability has been studied. Immobilization by covalent bonding on sepharose and silica afforded a maximum of 380 and 40 IU/g activity, respectively,whereas sol 13gel entrapment provided a maximum of 150 IU/g activity in dry powder. The immobilized enzyme displayed excellent stability in the pH range of 4 1310 and even at higher temperature, i.e., 50 136

Enantioselectivity modulation through immobilization of Arthrobacter sp. lipase: Kinetic resolution of fluoxetine intermediate

Arthrobacter sp. lipase (ABL, MTCC no. 5125) has been identified for its excellent performance in kinetic resolution of a number of drug intermediates. ABL free enzyme provided product II and V (ee < 95%) from racemic fluoxetine intermediate (I and IV) compared to its cell biomass in naturally immobilized state (ee < 98%). To overcome this problem and obtaining high enantioselectivity (R isomer ee 99%), ABL enzyme was modulated by immobilization using various methods vis-`a-vis substrate modification (Scheme 2). Immobilized enzyme obtained by hydrophobic binding provided 6710–7720 U/g, covalent binding 200 U/g, and sol–gel entrapment 65–110 U/g activity. Substantial improvement in enantioselectivity was obtained using acylates of ethyl 3-hydroxy 3-phenylpropanoate a fluoxetine drug intermediate (R isomer ee from 93 to 99% and E from 43 to 127–473) at 29–45% conversion in fixed time period of 21 h, indicating thereby some change in conformation of ABL immobilized enzyme. The ABL immobilized by covalent binding and sol–gel entrapment has demonstrated reasonable superiority over the free ABL in enantioselectivity as well as over all rate of hydrolysis. Immobilized enzymes prepared by covalent and entrapment methods have shown excellent operational stability and used for 10 cycles without loss in activity and the technique can be upscaled for process development